final program.qxd - Parallels Plesk Panel

EDITORIAL 

Dear Madam, Dear Sir, 

It is my pleasure to welcome you to the 14th International Symposium on HIV & Emerging 

Infectious Diseases taking place in Toulon "Palais Neptune" from June 21-23, 2006. 

You already know this event which, with time and thanks to everyone's implication, has found 

its place in practitioners' and scientists' agendas. This new edition keeps the same successful 

recipes as in previous years: prestigious speakers, welcoming ambiance, various exchanges, 

practical and theoretical data… 

As in 2004, the well-known members of the Steering and Scientific Committees have been 

individually responsible for various sessions in the program, and this allowed us to build these 

particularly captivating sessions, all centered around patients' care. 

Visitors are usually very pleased with their journey in Toulon. We are determined to welcome 

them even better to our "French Riviera" and to the city of Toulon which always does its best 

to be pleasant. 

Welcome again to Toulon ! 

Madame, Monsieur, 

C'est avec plaisir que je vous accueille à ce 14 e Symposium International sur le VIH et les 

Maladies Infectieuses Emergentes (ISHEID), qui se tient au Palais des Congrès de Toulon, du 

21 au 23 Juin 2006. 

Vous connaissez déjà cette manifestation qui, au fil du temps et grâce à l'implication de tous, 

a trouvé sa place dans l'agenda des praticiens et chercheurs. Nous avons conservé, pour 

cette nouvelle édition, les principes qui ont fait le succès des précédentes : des orateurs 

prestigieux, une ambiance chaleureuse, des échanges nombreux, des données à la fois 

pratiques et théoriques… 

Comme précédemment, les experts nationaux et internationaux des Comités d'Organisation 

et Scientifique ont été individuellement en charge de l'organisation des différentes parties des 

sessions, et nous leur devons ce programme captivant "centré autour du patient". 

Je tiens à remercier ici l'implication de tous et toutes vers un seul but: un congrès 'ISHEID' 

toujours meilleur! Un grand merci donc aux partenaires de l'industrie et aux orateurs sans 

lesquels rien n'existerait... 

Les congressistes sont habituellement très satisfaits de leur venue à Toulon, nous sommes 

décidés à les accueillir toujours mieux sur notre "French Riviera" et dans une ville qui fait son 

maximum pour encore plus s'embellir. 

Bienvenue à nouveau à Toulon ! 

Alain Lafeuillade, MD 

“ Focusing FIRST on PEOPLE “ 2 w w w . i s h e i d . c o m

• CHAIRMAN 

Alain LAFEUILLADE, Toulon - FRA 

• ORGANIZING COMMITTEE 

Jean-François DELFRAISSY, Paris - FRA 

Robert GALLO, Baltimore - USA 

José GATELL, Barcelona - ESP 

Denis LACOSTE, Bordeaux - FRA 

Jean-Marie LANG, Strasbourg - FRA 

Gilles PEYTAVIN, Paris - FRA 

Jacques REYNES, Montpellier - FRA 

Christine ROUZIOUX, Paris - FRA 

Catherine TAMALET, Marseille - FRA 

Stefano VELLA, Roma - ITA 

• SCIENTIFIC COMMITTEE 

Dominique BLANC, Marseille - FRA, Emmanuel DELBEKE, Toulon - FRA 

Jean-Albert GASTAUT, Marseille - FRA, Gilles HITTINGER, Toulon - FRA 

Jean-Pierre de JAUREGUIBERRY, Toulon - FRA, Leondios KOSTRIKIS, Nicosia - CYP 

Jean-Michel MOLINA, Paris - FRA, Yves MOUTON, Tourcoing - FRA 

Mark NELSON, London - GBR, Giuseppe PANTALEO, Lausanne - SUI 

Cécile POGGI, Toulon - FRA, Alain RIEU, Toulon - FRA 

Paolo RIZZARDI, Milano - ITA, Lidia RUIZ, Barcelona - ESP 

Vincente SORIANO, Madrid - ESP, Hans-Jurgen STELLBRINK, Hamburg - GER 

Giuseppe TAMBUSSI, Milano - ITA, Jean-Claude TARDY, Lyon - FRA 

• SCIENTIFIC SECRETARIAT 

Doctor Alain LAFEUILLADE 

Infectiology Unit, Chalucet Hospital - 83056 Toulon, France 

Ph: + 33 (0)4 94 22 77 41 

Fax: + 33 (0)4 94 92 67 47 

E-mail: toulon2006@club-internet.fr 

• LOGISTIC AND TECHNICAL ORGANIZATION 

OVERCOME 

3-5, boulevard Paul-Emile Victor 

92523 Neuilly-sur-Seine, France 

Ph: + 33 (0)1 41 92 01 20 

Fax: + 33 (0)1 46 41 05 21 

E-mail : hivcongress@overcome.fr 


PRACTICAL INFORMATION - INFORMATIONS PRATIQUES 

• VENUE OF THE CONGRESS - LIEU DU CONGRÈS 

International Congress Centre: PALAIS NEPTUNE - Place de Besagne, 83070 Toulon, France 

Ph: + 33 (0)4 98 00 83 83 - Fax: + 33 (0)4 98 00 83 62 - www.congresneptune.com 

• LOGISTIC AND TECHNICAL ORGANIZATION - ORGANISATION LOGISTIQUE & TECHNIQUE 

OVERCOME: 3-5, boulevard Paul-Emile Victor, 92523 Neuilly-sur-Seine, France 

Ph: + 33 (0)1 41 92 01 20 - Fax: + 33 (0)1 46 41 05 21 - E-mail: hivcongress@overcome.fr 

• REGISTRATION - INSCRIPTION 

On-site Delegate registration - Inscription congressiste sur place 350 € 

Residents - Internes 70 € 

AIDS's association members* - Adhérents associations SIDA* 70 € 

Students* - Nurses* - Etudiants* - Infirmières* 35 € 

*A certificate is required - Joindre une attestation 

• EXHIBITION - EXPOSITION 

Pharmaceutical companies and scientific book publishers will display their products at the exhibition area located 

at the Congress Centre Palais Neptune level 1 - Une exposition de firmes pharmaceutiques et éditeurs de livres 

scientifiques est située au niveau 1 du centre de Congrès, Palais Neptune. 

Opening Hours - Heures d’ouverture de l’exposition 

Wednesday June 21, 2006: 08.00 - 19.30 

Thursday June 22, 2006: 08.00 - 19.00 

Friday June 23, 2006: 08.00 - 17.30 

• POSTERS - POSTERS 

Scientific posters are displayed throughout the congress at level 1. Authors are kindly requested to stand close to 

their poster during the breaks. The best poster award will be announced on Friday June 23, 2006 at 10.30 am by 

VIRCO - Des posters scientifiques sont exposés durant le congrès au niveau 1. Les auteurs sont priés de rester 

près de leur poster pendant les pauses. Le prix du meilleur poster sera remis le vendredi 23 juin 2006 à 10h30 par 

VIRCO. 

• OFFICIAL LANGUAGE - LANGUE OFFICIELLE 

The official language of the meeting is English. Simultaneous translation English into French and French into English 

will be provided for each session - La langue officielle du Congrès est l'anglais. Une traduction simultanée de 

l'anglais vers le français et du français vers l'anglais est prévue pour chaque session. 

• MOBILE PHONES - TÉLÉPHONES PORTABLES 

Mobile phones should be switched off during the sessions. 

Les téléphones portables doivent être éteints durant toutes les sessions. 

• TRANSPORTATION - TRANSPORT 

On international routes: AIR FRANCE offices and call centers throughout the World will offer preferential fares from your country of departure. Appropriate published fares 

from french overseas departments and territories apply. Your nearest Air France Office and call centers : http://www.airfrance.com 

On the domestic network within continental France: This original document will entitle you a reduction of up 45% on the regular full fare in economy class for a round trip 

journey (subject to conditions) on the Air France continental domestic network for this event. To book your electronic ticket please contact the Air France call center from 

within France 0 820 820 820* or your nearest Air France office http://www.airfrance.fr or Overcome +33 (0)1 41 92 01 20. Members of partner carrier's loyalty programme 

will receive miles on their programme when using Air France flights. Check details with your Air France office. 

Domestic and international approved number: AXZE SE 5766 - Validity from June 18 to June 26, 2006 

For Air France Offices : discount registered on GGAIRAFEVENTNEGO 

Sur le réseau France métropolitaine : Ce document original vous permettra d'obtenir jusqu'à 45 % de réduction sur le plein tarif en classe économique (soumis à conditions) 

pour vous rendre à la manifestation. Contacter le 0 820 820 820* pour obtenir votre billet électronique ou l'Agence Overcome +33 (0)1 41 92 01 20. 

Sur le réseau international : Les agences et centres de réservation AIR FRANCE du monde entier vous proposeront des tarifs préférentiels au départ de votre pays. Pour 

les DOM-TOM : tarifs publiés Air France adaptés. Liste des Agences et centres de réservation Air France sur Internet : 

http:// www.airfrance.com. Les programmes de fidélisation des compagnies partenaires permettent d'accumuler des "miles" en utilisant des vols Air France. 

Renseignements auprès de votre agence Air France. 

Homologation réseau métropole et Internationale AIR FRANCE : AXZE SE 5766 - validité du 18 Juin 2006 au 26 Juin 2006 

Réductions enregistrées sur GGAIRAFEVENTNEGO pour Air France. 


SUMMARY - SOMMAIRE 

Scientific Program - Programme Scientifique 

• Program at a glance........................................................................................ 6 

Résumé du programme 

• Wednesday June 21, 2006 ........................................................................ 7 

Mercredi 21 juin 2006 

• Thursday June 22, 2006 .............................................................................. 11 

Jeudi 22 juin 2006 

• Friday June 23, 2006...................................................................................... 15 

Vendredi 23 juin 2006 

Posters Presentations - Présentations Posters .......................... 18 

Oral Presentations Abstracts 

Résumés des communications orales ................................................ 31 

Posters Abstracts - Résumés des Posters........................................ 83 

Free Oral Presentations Abstracts 

Résumés des communications orales libres ................................ 243 

Special Lectures & Symposia Abstracts 

Résumés des lectures et symposia ...................................................... 273 

Acknowledgements - Remerciements .................................................. 287 

Sponsors - Partenaires............................................................ 288 

Oral presentations can be given either in French or English. Simultaneous 

translation is available for each session. Please ask for your translation 

headphone at the congress welcome desk. 

Les communications orales peuvent être données à la fois en français et en 

anglais. Une traduction simultanée est prévue pour chaque session. Merci de 

vous munir de votre casque de traduction à l’accueil du congrès. 

*An identity card will be requested - Une pièce d’identité vous sera demandée 


PROGRAM AT A GLANCE 


WEDNESDAY JUNE 21, 2006 - MERCREDI 21 JUIN 2006 

• 09.00 

Opening Welcome Desk - Ouverture de l’accueil 

• 10.45 - 11.00 

Opening Ceremony - Cérémonie d’ouverture 

• 11.00 - 12.00 LECTURE VAUBAN AMPHITHEATER 

LECTURE ON “AVIAN FLU” - LECTURE SUR LA GRIPPE AVIAIRE 

• PL 1 Bird Flu and Human Risk - Grippe Aviaire et risque humain 

ALICE CROISIER, WHO GENEVA - SUI 

12.00 - 13.00 

Break, Posters, Exhibition - Pause, posters, exposition 

• 12.00 - 13.00 MEET & EAT PARALLEL SESSION COLBERT ROOM 

Meet & Eat with the Experts (on invitation) - Déjeuner-débat (sur invitation) 

UNDETECTABILITY: CASE STUDY DISCUSSION 

L’INDETECTABILITÉ : DISCUSSION AUTOUR DE CAS CLINIQUES 

CHAIRPERSONS: ISABELLE POIZOT-MARTIN, MARSEILLE - FRA & JEAN-CLAUDE TARDY, LYON - FRA 

• Treatment of Naïve Patient: Impact of Undetectability on Medium and 

Long-term Survival? - Patient naïf : impact de l’indétectabilité sur la survie 

à moyen et long termes ? 

• Patient with Detectable Viral Load and CD4>350: Which Strategy? 

Patient avec une charge virale détectable et CD4>350 : conduite à tenir ? 

• Patient with Persistence Viremia Despite an Optimal ARV Treatment: 

Which Attitude to Adopt? 

Patient avec une virémie persistante malgré un traitement antirétroviral 

optimal : que faire ? 

• 13.00 - 14.30 SESSION VAUBAN AMPHITHEATER 

THE PATIENT IS OUR GOAL - LE PATIENT EST NOTRE PRÉOCCUPATION 

CHAIRPERSONS: DOMINIQUE BLANC, MARSEILLE - FRA & DENIS LACOSTE, BORDEAUX - FRA 

• OP 1.1 

Role of Care Givers - Rôle des soignants 

DENIS LACOSTE, BORDEAUX - FRA 

• OP 1.2 Still a Role for Activists? - Reste-t-il un rôle pour les associations ? 

CHRISTIAN SAOÛT, AIDES PARIS - FRA 

• OP 1.3 

• OP 1.4 

Public Health and Social Science in Clinical Research: the Interest of 

a Multidisciplinary Approach - Santé publique et sciences sociales en 

recherche clinique : intérêt d’une approche multi-disciplinaire 

FRANCE LERT, SAINT-MAURICE - FRA 

An Anthropological Approach of HIV/AIDS 

Approche anthropologique du VIH/SIDA 

STÉPHANIE MULOT, TOULOUSE - FRA 



• 13.00 - 14.30 PARALLEL SESSION COLBERT ROOM 

RESEARCH PRIORITIES IN HIV - PRIORITÉS EN RECHERCHE VIH 

CHAIRPERSONS: LUC PERRIN, GENEVA - SUI & GILLES HITTINGER, TOULON - FRA 

• OP 2.1 

• OP 2.2 

• OP 2.3 

• OP 2.4 

In Epidemiology - En épidémiologie 

AMANDA MOCROFT, LONDON - GBR 

In Virology - En virologie 

LUC PERRIN, GENEVA - SUI 

In Immunology - En immunologie 

MARIE-LISE GOUGEON, PARIS - FRA 

In Therapy - En thérapeutique 

JEAN-FRANÇOIS DELFRAISSY, PARIS - FRA 

• 14.30 - 16.00 SYMPOSIUM VAUBAN AMPHITHEATER 

QUANTITATIVE HIV-1 RESISTANCE TESTING WITH CLINICAL CUT-OFF: A NEW 

TOOL IN THERAPY MANAGEMENT? - COMMENT L’ANALYSE QUANTITATIVE DE 

LA RÉSISTANCE DU VIH-1 ET LES SEUILS D’INTERPRÉTATION CLINIQUES 

PEUVENT-ILS AIDER À LA GESTION THÉRAPEUTIQUE ? 

CHAIRPERSONS: ALAIN LAFEUILLADE, TOULON - FRA & CATHERINE TAMALET, MARSEILLE - FRA 

• SS 1.1 

• SS 1.2 

• SS 1.3 

• SS 1.4 

The Importance of Resistance Testing in Daily Praxis: the Spread of Multi 

Resistant Viruses and the Hurdles of Defining a New Therapy 

L’importance des analyses de résistance dans le suivi clinique : la propagation 

de virus multi-résistants et les difficultés lors du choix d’une nouvelle thérapie 

VICENTE SORIANO, MADRID - ESP 

Improved Case Management using Clinical Cut-Offs 

La gestion thérapeutique utilisant les seuils d’interprétation cliniques : exemples 

JÜRGEN ROCKSTROH, BONN - GER 

Virtual Phenotype and Clinical Cut-Offs: What is Behind the Science and 

Technology - Phénotype virtuel et seuils d’interprétation cliniques: la science 

et la technologie 

JORGE VILLACIAN, MECHELEN - BEL 

Retrospective Analysis Performed at CHU Lille/Tourcoing and Prospective Study 

Analyse rétrospective réalisée au CHU Lille/Tourcoing 

LAURENCE BOCKET, TOURCOING - FRA 

Discussions and questions 

16.00 - 16.30 Break, Posters, Exhibition - Pause, posters, exposition 




PRIORITIES FOR INITIAL THERAPY 

QUELS POINTS MAJEURS POUR INITIER UN TRAITEMENT ? 

CHAIRPERSON: ALAIN LAFEUILLADE, TOULON - FRA 

• SS 2.1 

• SS 2.2 

• SS 2.3 

The Lessons we have Learned over the Last Decade 

Les enseignements à tirer des 10 dernières années 

PIERRE DELLAMONICA, NICE - FRA 

Differentiating between Different Options 

Optimiser son choix entre différentes options thérapeutiques 

MARC NELSON, LONDON - GBR 

The Future of Therapy 

Le futur des thérapies 

ROLAND LANDMAN, PARIS - FRA 


NEW FRONTIERS IN HIV - NOUVELLES FRONTIÈRES DANS L’INFECTION À VIH 

CHAIRPERSONS: CATHERINE TAMALET, MARSEILLE - FRA & ANTOINE CHÉRET, TOULON - FRA 

• OP 3.1 

• OP 3.2 

• OP 3.3 

• OP 3.4 

• OP 3.5 

The Outcome of Children HIV-Infected at the Beginning of the Epidemics 

Devenir des enfants infectés par le VIH au début de l’épidémie 

ALBERT FAYE, PARIS - FRA 

Interactions Between HSV & HIV - Interactions Herpès Virus et VIH 

ANNA MARIA GERETTI, LONDON - GBR 

Neurocognitive Impairment in the HAART Era 

Atteintes neurocognitives à l’ère des multi-thérapies anti-VIH 

VALERIO TOZZI, ROMA - ITA 

Fertility Options in HIV-Infected Patients 

Aide médicale à la procréation dans l’infection à VIH 

JEANINE OHL, STRASBOURG - FRA 

Non-AIDS Defining Cancers in the Era of HAART 

Cancers ne définissant pas le SIDA à l’ère des multi-thérapies 

NANCY CRUM-CIANFLONE, SAN DIEGO - USA 


FREE ORAL PRESENTATIONS - COMMUNICATIONS LIBRES 

CHAIRPERSONS: GUISEPPE TAMBUSSI, MILANO - ITA & STEFANO VELLA, ROMA - ITA 

• FP 1.1 

In Vivo Emergence of RANTES-Resistant Simian Immunodeficiency Virus 

in Pig-Tailed Macaques Coinfected with Human Herpesvirus 6A 

ANGELIQUE BIANCOTTO, BETHESDA - USA 



• FP 1.2 

• FP 1.3 

• FP 1.4 

• FP 1.5 

• FP 1.6 

• FP 1.7 

• FP 1.8 

• FP 1.9 

• FP 1.10 

• FP 1.11 

Natural Suppressors, HIV-1 Viral Suppression in the Absence of Therapy 

MOHAMMAD SAJADI, BALTIMORE - USA 

An in vitro System for HIV-1 Selective Transmission using Human Genital 

Epithelial cells 

ZHIWEI WU, NANJING - CHN 

V1V2 loop length variation during HIV-1 Infection 

MARCEL CURLIN, SEATTLE - USA 

Generic Screening Test for HIV Infection 

FRANÇOIS SIMON, ROUEN - FRA 

Analysis of Plasma Cytokines in Immunological and Virological Discordant HIV-1 

Infected Patients by Microarray System: a pilot study 

DESHRATN ASTHANA, MIAMI - USA 

HIV-1 Subtype C Viruses Rapidly Develop K65R Resistance to Tenofovir 

in Cell Culture 

MARK WAINBERG, MONTREAL - CAN 

Detection of Low Frequency HIV-1C Drug Resistant Variants in Treatment 

Exposed Patients 

HARRIET OKATCH, BOSTON - USA 

HCV-Associated B Cell Clonalities in the Liver do not Carry the t(14;18) 

Chromosomal Translocation 

DOMENICO SANSONNO, BARI - ITA 

Replication-Competent Platforms for Lassa Fever Vaccine Design 

IGOR LUKASHEVICH, BALTIMORE - USA 

Bats as Potential Reservoirs for Ebola Virus 

XAVIER POURRUT, FRANCEVILLE - GAB 


THURSDAY JUNE 22, 2006 - JEUDI 22 JUIN 2006 


NEW ANTIRETROVIRAL DRUGS - NOUVEAUX ANTI-RÉTROVIRAUX 

CHAIRPERSONS: JACQUES REYNES, MONTPELLIER - FRA & JOEP LANGE, AMSTERDAM - NED 

• OP 4.1 

• OP 4.2 

• OP 4.3 

• OP 4.4 

• OP 4.5 

• FP 0.1 

• FP 0.2 

New Antiretrovirals in the Pipeline: from Already Known Targets to Integrase Inhibitors 

Les anti-rétroviraux en développement : 

des inhibiteurs de cibles déjà connues aux inhibiteurs d’intégrase 

STEFANO VELLA, ROMA - ITA 

Development of AVX754 - Développement du AVX754 

SUSAN COX, RICHMOND - AUS 

Update on TMC114 - Actualités sur TMC114 

DIEGO MIRALLES, MECHELEN - BEL 

Update on Maraviroc Studies - Le point des études sur le Maraviroc 

CHRIS HITCHCOCK, SANDWICH - GBR 

Recent Data on PA457 Maturation Inhibitor 

Données récentes sur l’inhibiteur de maturation, PA457 

DAVID MARTIN, MARYLAND - USA 

Thiovir Exhibits Broad-Spectrum Antiviral Activity Against Human and Avian 

Influenza Viruses, Human Immunodeficiency Viruses, and Herpes Simplex 

Viruses - Thiovir démontre une activité antivirale large spectre contre les virus 

de la grippe aviaire humaine, les VIH et les HSV 

SHANI WANINGER, SAN DIEGO - USA 

Preclinical Development of a Novel Long-Lasting HIV-1 Fusion Inhibitor - Développement 

pré-clinique d'un nouvel inhibiteur de fusion du VIH-1 à libération prolongée 

DONG XIE, CHONGQING - CHN 

10.30 - 11.00 



HOW TO MANAGE GETTING OLDER WITH HIV - BIEN VIEILLIR AVEC LE VIH 

CHAIRPERSONS: CHRISTINE KATLAMA, PARIS - FRA & ALAIN LAFEUILLADE, TOULON - FRA 

• SS 3.1 

• SS 3.2 

• SS 3.3 

Brain and HIV 

Cerveau et VIH 

JACQUES GASNAULT, KREMLIN-BICÊTRE - FRA 

Long-Term Cardiovascular Troubles of HIV Patients 

Troubles cardiovasculaires à long terme des patients VIH 

DAVID ZUCMAN, SURESNES - FRA 

Cancer and HIV - Cancer et VIH 

CHRISTINE KATLAMA, PARIS - FRA 



12.30 - 14.00 

Lunch, courtesy of - Déjeuner offert par Bristol-Myers Squibb 


SUMMARY OF ADVANCES IN HIV DURING THE LAST YEAR 

RÉSUMÉ DES AVANCÉES DANS L’INFECTION À VIH SUR L’ANNÉE ÉCOULÉE 

CHAIRPERSONS: ALAIN RIEU, TOULON - FRA & JOSÉ GATELL, BARCELONA - ESP 

• OP 5.1 

• OP 5.2 

• OP 5.3 

Virology - Virologie 

LEONDIOS KOSTRIKIS, NICOSIA - CYP 

Therapy & New ARV Interactions - Anti-rétroviraux et nouvelles interactions 

JOSÉ GATELL, BARCELONA - ESP 

Immunology - Immunologie 

GUIDO POLI, MILANO, ITA 


HIV IN TOMORROW EUROPE - LE VIH DANS L’EUROPE DE DEMAIN 

CHAIRPERSONS: YVES MOUTON, TOURCOING - FRA & JEAN-CLAUDE TARDY, LYON - FRA 

• OP 6.1 

• OP 6.2 

• OP 6.3 

• OP 6.4 

Social Representations of HIV/AIDS in Central and Eastern Europe 

Représentations Sociales du VIH/SIDA dans l’Europe Centrale et de l’Est 

ROBIN GOODWIN, LONDON - GBR 

Molecular Epidemiology of HIV-1 Infection: Tracing how the Epidemic Spreads 

Epidémiologie moléculaire de l’infection à VIH-1 : suivi de l’extension épidémique 

DIMITRIOS PARASKEVIS, ATHENS - GRE 

HIV Epidemics in Ukraine - Epidémie VIH en Ukraine 

PAVLO KYRYCHENKO, VINNITSA - UKR 

The Epidemiology of HIV & STDs in Slovenia - Epidémie VIH et IST en Slovénie 

IRENA KLAVS, LJUBLJANA - SLO 


MANAGEMENT OF HIV: WHAT KEY DRIVERS FOR A LONG TERM SUCCESS? 

PRISE EN CHARGE DU VIH : QUELLES CLÉS POUR UN SUCCÈS DURABLE ? 

CHAIRPERSONS: ALAIN LAFEUILLADE, TOULON - FRA & GILLES PEYTAVIN, PARIS - FRA 

• SS 4.1 

• SS 4.2 

• SS 4.3 

• SS 4.4 

Pharmacologic Prerequisites - Les pré-requis pharmacologiques 

GILLES PEYTAVIN, PARIS - FRA 

Resistance at Stake - Les enjeux de la résistance 

JACQUES IZOPET, TOULOUSE - FRA 

From Lipids to Cardiovascular Risk - Des lipides au risque cardio-vasculaire 

JEAN-LUC MEYNARD, PARIS - FRA 

Future Trends - Les orientations pour demain 

ALAIN LAFEUILLADE, TOULON - FRA 



16.30 - 17.00 



ANTIRETROVIRAL STRATEGIES - STRATÉGIES ANTI-RÉTROVIRALES 

CHAIRPERSONS: ALAIN LAFEUILLADE, TOULON - FRA & MARK NELSON, LONDON - GBR 

Question 1: We can now Avoid Lipodystrophy/Metabolic Complications in Newly Treated Patients 

Il est maintenant possible d’éviter la lipodystrophie et les complications 

métaboliques chez les patients nouvellement traités 

• OP 7.1.1 Pros - Pour : CHRISTINE KATLAMA, PARIS - FRA 

• OP 7.1.2 Cons - Contre : ISABELLE POIZOT-MARTIN, MARSEILLE - FRA 

Question 2: Triple nRTI Combinations are Obsolete 

Les triples combinaisons d’inhibiteurs nucléosidiques de la RT sont obsolètes 

• OP 7.2.1 Pros - Pour : JAN VAN LUNZEN, HAMBURG - GER 

• OP 7.2.2 Cons - Contre : MARK NELSON, LONDON - GBR 

Question 3: We must Switch Early Patients with Detectable Viremia 

Nous devons switcher rapidement les patients avec virémie détectable 

• OP 7.3.1 Pros - Pour : YAZDANPANAH YAZDAN, TOURCOING - FRA 

• OP 7.3.2 Cons - Contre : RITA MURRI, ROMA - ITA 

Question 4: Entry Inhibitors Have to be Spared for Advanced Stages 

Les Inhibiteurs d’entrée doivent être réservés aux stades avancés 

• OP 7.4.1 Pros - Pour : JÜRGEN ROCKSTROH, BONN - GER 

• OP 7.4.2 Cons - Contre : GIUSEPPE TAMBUSSI, MILANO - ITA 



CHAIRPERSONS: PAOLO RIZZARDI, MILANO - ITA & JEAN-CLAUDE TARDY, LYON - FRA 

• FP 2.1 

• FP 2.2 

• FP 2.3 

• FP 2.4 

Long-Term Non-Progression in HIV Infection: 

Experience of the Australian cohort 

JOHN KALDOR, SYDNEY - AUS 

HIV-1 and HIV-2 DNA in the Early Phase of Infection: in Vitro Quantification 

by real time PCR using a combined HIV-1+ HIV-2 plasmid 

FRANÇOIS SIMON, ROUEN - FRA 

HAART in Sub-Saharan Countries: the Panacea? 

CHRISTIAN VILADENT, LAUSANNE - SUI 

Stigmatization and Adherence to HAART among two Cohorts of HIV Positive 

Patients in Bamako and Ouagadougou 

ANDRÉ NGAMINI, MONTREAL - CAN 



• FP 2.5 

• FP 2.6 

• FP 2.7 

• FP 2.8 

Morbidity and Mortality by Baseline CD4 Cell Count During the First Months 

Following HAART Initiation in HIV-infected Adults in Abidjan, Côte d'Ivoire 

DESMORYS RAOUL MOH, ABIDJAN - CIV 

Tolerability of Antiretroviral Drugs Used in Post Exposure Prophylaxis 

after Sexual Assault in the Cape Metropole Region 

PIERRE MUGABO, CAPE TOWN - SAF 

Hepatic Steatosis in HIV and Hepatitis C Virus Coinfected Patients 

Receiving Antiretroviral Therapy 

VALÉRIE MARTINEZ, PARIS - FRA 

Radata - An Internet-based System for Salvage Patients with the Possibility 

of Expert Advice 

THORE LORENZEN, HAMBURG - GER 


FRIDAY JUNE 23, 2006 - VENDREDI 23 JUIN 2006 


EMERGING INFECTIOUS DISEASES - MALADIES INFECTIEUSES ÉMERGENTES 

CHAIRPERSONS: ALAIN RIEU, TOULON - FRA & JEAN-CLAUDE TARDY, LYON - FRA 

• OP 8.1 

• OP 8.2 

• OP 8.3 

• OP 8.4 

• FP 0.3 

Primate-to-Human Retroviral Transmission 

Transmission de retrovirus du primate vers l’homme 

LISA JONES-ENGEL, SEATTLE - USA 

Epidemiology & Natural History of West Nile Virus Disease 

Epidémiologie et Histoire Naturelle des infections à Virus West Nile 

JAMES SEJVAR, ATLANTA - USA 

Avian Influenza: the Veterinarian Perspective 

Grippe Aviaire : perspective vétérinaire 

ARJAN STEGEMAN, UTRECHT - NED 

Dengue Disease in the French West Indies 

La Dengue dans les Antilles Françaises 

CHRISTOPHE PEYREFITTE, MARSEILLE - FRA 

Viral Shedding of Avian Influenza Virus in Recovered Patients from Thailand 

Excrétion virale chez les patients Thaïlandais ayant guéri de la Grippe Aviaire 

RUENGPUNG SUTTHENT, BANGKOK - THA 



CHAIRPERSONS: LEONDIOS KOSTRIKIS, NICOSIA - CYP & JEAN-PIERRE DE JAUREGUIBERRY, TOULON - FRA 

• FP 3.1 

• FP 3.2 

• FP 3.3 

• FP 3.4 

An HIV-1 Peptide-based Vaccine Inducing Cross-subtype Immunity in Macaques 

FRANCISCO DIAZ-MITOMA, OTTAWA - CAN 

Glycosylated Recombinant Simian IL-7 Induces Sustained Increased in Peripheral 

Naïve and Memory T cell Counts in Healthy Rhesus Macaques: a New Possibility 

for Immune Reconstitution 

STÉPHANIE BEQ, PARIS - FRA 

Effect of Oligonucleotide Adjuvant on the Immune Modulation Induced by HIV-1 

Whole Inactivated Vaccine in Antiretroviral Naïve HIV-1 Infected Patients 

MARIO CLERICI, MILANO - ITA 

Therapeutic Tat-Vaccination in Chronic HIV-Infection 

DANIEL ZAGURY, PARIS - FRA 




HIV-ASSOCIATED FACIAL LIPOATROPHY AND THERAPEUTIC APPROACHES 

LIPOATROPHIE FACIALE DES PATIENTS SEROPOSITIFS POUR LE VIH ET 

APPROCHES THERAPEUTIQUES 

CHAIRPERSON: PASCALE LECLERCQ, GRENOBLE - FRA 

• SS 5.1 

• SS 5.2 

• SS 5.3 

HIV-Associated Lipodystrophy Syndrome: Pathophysiology 

Physiopathologie du syndrome lipodystrophique 

JACQUELINE CAPEAU, PARIS - FRA 

Therapeutic Strategies to Treatment of HIV-Facial Lipoatrophies 

Stratégies thérapeutiques de la correction des lipoatrophies faciales 

CHRISTOPHE COMPAGNON, MARSEILLE - FRA 

Practical Management: The L-Polylactic Acid Case 

Prise en charge en pratique : l’exemple de l’acide L-polylactique 

MARC DOLIVO, PARIS - FRA 


Best Poster Award offered by VIRCO BVBA 

Remise du Prix du Meilleur Poster offert par VIRCO BVBA 


IMPACT OF THE NEW ARV AGENTS IN THE THERAPEUTIC STRATEGY OF HIGHLY 

TREATED EXPERIENCE PATIENTS - APPORT DES NOUVEAUX ANTIRETROVIRAUX 

DANS LA PRISE EN CHARGE DES PATIENTS MULTITRAITES 

CHAIRPERSON: ALAIN LAFEUILLADE, TOULON - FRA 

• SS 6.1 

• SS 6.2 

• SS 6.3 

How to Improve the Use of the New ARV Agents? 

Comment améliorer l’utilisation des nouveaux ARV ? 

ANNE-MARIE TABURET, PARIS - FRA 

Is there HIV-1 Evolution in Cellular Reservoirs during Prolonged 

Suppressive HAART? - Y a t-il une évolution du VIH-1 dans les réservoirs 

cellulaires lors d’un traitement antirétroviral efficace ? 

JACQUES IZOPET, TOULOUSE - FRA 

Tipranavir is a Potent Protease Inhibitor with an Activity 

against IP-Resistant Forms of HIV-1 - Le Tipranavir est un puissant inhibiteur 

de protéase avec une excellente activité contre les formes résistantes du VIH-1 

MARK WAINBERG, MONTREAL - CAN 





VIRAL HEPATITIS - HÉPATITES VIRALES 

CHAIRPERSONS: DOMINIQUE SALMON-CÉRON, PARIS - FRA & ANTOINE CHÉRET, TOULON - FRA 

• OP 9.1 

• OP 9.2 

• OP 9.3 

• OP 9.4 

New Developments in Hepatitis B Treatment 

Actualités dans le traitement des Hépatites B 

STEPHANOS HADZIYANNIS, ATHENS - GRE 

Improving Anti-HCV Therapy - Comment améliorer nos traitements anti-VHC 

STANISLAS POL, PARIS - FRA 

Future Options in Nonresponders and Relapsers After Current Anti-HCV Therapy 

Options futures pour les non répondeurs ou rechuteurs après traitement actuel anti-VHC 

MARC BOURLIÈRE, MARSEILLE - FRA 

Drug Administration in HIV-infected Patients with Cirrhosis 

Précautions thérapeutiques chez les patients VIH cirrhotiques 

DOMINIQUE SALMON-CÉRON, PARIS - FRA 

• FP 0.4 

• FP 0.5 

Primary Resistance of a Novel Hepatitis B Virus Variant to Adefovir 

Résistance primaire à l'Adéfovir d'un nouveau variant viral de l'hépatite B 

OLIVIER SCHILDGEN, BONN - GER 

The Epidemic History of Hepatitis C among Drug Users in Flanders, Belgium 

Histoire épidémiologique de l'infection à VHC chez les toxicomanes de Flandres, 

Belgique 

CATHARINA MATTHEÏ, LEUVEN - BEL 

15.30 - 16.00 



HIV PREVENTION & VACCINE - PRÉVENTION DU VIH ET VACCINS 

CHAIRPERSONS: ALAIN LAFEUILLADE, TOULON - FRA & DOMINIQUE BLANC, MARSEILLE - FRA 

• OP 10.1 Progress in Microbicide Development 

Progrès dans la mise au point de microbicides 

ZEDA ROSENBERG, SILVER SPRING - USA 

• OP 10.2 HIV Vaccine Research: Challenges and Difficulties 

Vaccin contre le VIH : défis et difficultés 

MARC GIRARD, LYON - FRA 

• OP 10.3 Current Advances in HIV Vaccine Development 

Vaccin contre le HIV : état actuel des recherches 

PATRICIA D’SOUZA, BETHESDA - USA 

• OP 10.4 Updated data on DermaVir 

Données récentes concernant le DermaVir 

FRANCO LORI, PAVIA - ITA 

17.30 Closing - Clôture 


POSTERS PRESENTATIONS - PRESENTATIONS POSTERS 

Track I: Epidemiology and Prevention 

• PP 1.1 

• PP 1.2 

• PP 1.3 

• PP 1.4 

• PP 1.5 

• PP 1.6 

• PP 1.7 

• PP 1.8 

• PP 1.9 

• PP 1.10 

• PP 1.11 

• PP 1.12 

• PP 1.13 

• PP 1.14 

Hospitalization of Extra-European Union Children: 

a five-year survey from Bologna, Northern Italy 

ROBERTO MANFREDI, BOLOGNA, ITA 

AIDS Orphans: Assessment of Families in Crisis 

MEGAN GATLIN, VALLEJO, USA 

Immigration and HIV Infection in Northern Italy. Inpatient Admissions, 

2000-2005 


Impact of Migration on HIV/AIDS Situation in Nepal 

PRADIP TIMALSENA, KATHMANDU, NEP 

Rapid Shift from HIV-2 to HIV-1 in Police Officers in Guinea-Bissau, 

West Africa 

HANS NORRGREN, LUND, SWE 

Epidemiological Aspects of Morbus HIV in the Region Nis-Serbia 

BRANISLAV TIODOROVIC, NIS, SER AND MONTENEGRO 

Genetic Differences in the HIV-1 C2-V3-C3 Region Between Haiti and USA 

Isolates Indicate Differences in Adaptation at the Population Level 

BEATRIZ M. PEREZ-SWEENEY, NEW YORK, USA 

HIV Transmission in The Gambia and the West African Region 

ADEBAYO AKINSIPE, BANJUL, GAM 

HIV/ HCV Transmission from HIV/HCV Co-infected Mothers to Infants 

IRINA SIMONOVA, MOSCOW, RUS 

Evaluation of Prevalence and Risk of HBV, HCV and HIV Infections 

in Health Care Workers 

GRATIANA CHICIN, TIMISOARA, ROM 

HIV/STD Prevention Need Assessment among Sex Workers in Nepal 

BIRENDRA POUDEL, KATHMANDU, NEP 

Co-morbidity of HIV, Hepatitis B, and Syphilis, among Victims of Sexual 

Assaults in Transkei Region, South Africa 

BANWARI MEEL, MTHATHA, SAF 

Prevalence of HIV in Mthatha area of South Africa, as Estimated from 

Testing of Rape Victims 

BANWARI MEEL, MTHATHA, SAF 

Screening for HIV-infection and Mother-to-child Transmission of HIV among 

Pregnant Women Attending a Maternity Ward in Dakar (Senegal) 

MOUSSA SARR, DAKAR, SEN 



• PP 1.15 

• PP 1.16 

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• PP 1.18 

• PP 1.19 

• PP 1.20 

• PP 1.21 

• PP 1.22 

• PP 1.23 

• PP 1.24 

• PP 1.25 

• PP 1.26 

• PP 1.27 

HIV Genotoyping on Filter Paper (DPS): 

a New Method for HIV Resistance Epidemiological Survey 

FRANÇOIS SIMON, ROUEN, FRA 

Low Performance of HIV-1 Serotyping in High HIV Epidemic Geographical 

Areas 

STEFANO BUTTÒ, ROMA, ITA 

In the Footsteps of the WHO - Rapid HIV Testing in America 

EUGENE MARTIN, NEW BRUNSWICK, USA 

The Spread of HIV-1 Resistance Mutations in the South of Russia 

ANDREY SHEMSHURA, ROSTOV-ON-DON, RUS 

Knowledge and Practice in Post-exposure HIV Prevention for Medical Staff 

in Moscow. YURI MARTYNOV, MOSCOW, RUS 

Study of the anti-HIV Recombinant Vaccinia Viruses 

IGOR BABKIN, KOLTSOVO, RUS 

Candidate Oral Vaccines against Hepatitis B Virus and Human 

Immunodeficiency Virus Based on Transgenic Tomato and Carrot Plants 

SERGEI SHCHELKUNOV, KOLTSOVO, RUS 

Comparative Investigation of the DNA-Vaccines against HIV based on 

Artificial Gene TBI 

IRINA BABKINA, KOLTSOVO, RUS 

Impact of a School-based HIV/AIDS Educational Intervention on Students' 

Behaviour Intentions in Ukraine 

PAVLO KYRYCHENKO, VINNITSA, UKR 

Foreign Citizens Admitted to the General Teaching Hospital of Bologna, 

North-Eastern Italy. An Epidemiological Clinical Survey 


Risk Factors for Human Herpesvirus 8 (KSHV/HHV-8) Viremia in AIDS 

Patients with Kaposi's Sarcoma 

LIGIA CAMERA PIERROTTI, SAO PAULO, BRA 

Morbidity Pattern of PLWA Receiving Emergency Care at PEPFAR 

Treatment Centre, University College Hospital, Ibadan 

SAMUEL OLOWOOKERE, BOSTON, USA 

AIDS Prevention Program for MSM: Findings from a Baseline Survey 

in Lahore Pakistan 

TANVIR AHMAD ZAVER ET AL., LAHORE, PAK 



• PP 1.28 

• PP 1.29 

• PP 1.30 

• PP 1.31 

• PP 1.32 

• PP 1.33 

Incidence of Atypical Mycobacteria in Sputum AFB Positive Patients with 

AIDS Presenting at a Tertiary Hospital in Mumbai 

MOHAMMAD KHALID, MUMBAI, IND 

Developing Partnerships between Non-Profit Health Providers and the 

Department of Health for the Delivery of Quality Primary Health Care, 

Including those Related to HIV and AIDS, in South Africa 

FIKILE NAOMI MBATHA, PIETERMARITZBURG, SAF 

Community Response to HIV/AIDS: Empowering Communities in HIV/AIDS 

Management 

BEATRICE CHOLA, LUSAKA, ZAM 

Pakistani Youth and their Risky Behavior on HIV/AIDS & Sexuality 

MUHAMMAD HANIF, LAHORE, PAK 

Models for Prevention & Treatment of PLWHA-Lessons from AMPATH 

(Academic Model for Prevention and Treatment of HIV/AIDS) 

Program in Western Kenya 

GICHOYA JUDY WAWIRA, ELDORET, KEN 

Model based on a Quantum Algorithm for the Study of HIV 

LEÓN ALEJANDRO, SANTIAGO, CHI 

Track II: HIV Basic Science 

• PP 2.1 

• PP 2.2 

• PP 2.3 

• PP 2.4 

• PP 2.5 

• PP 2.6 

Analysis of Polymorphism in the Protease and Reverse Transcriptase Genes 

of HIV type 1 CRF02_AG Subtypes from Drug-naïve Patients from 

Saint-Etienne, France 

THOMAS BOURLET, SAINT-ETIENNE, FRA 

Analysis of Full-length HIV-1 Subtype G Molecular Clones 

SANDRA PENELOPE FREITAS, LISBON, POR 

Broad Neutralization of Human Immunodeficiency Virus Type 1 by 

Monoclonal Antibody against C2 Region 

APICHAI SREEPIAN, BANGKOK, THA 

The Cobas Ampliprep/Cobas Taqman 48 HIV-1 Test is Compatible with the 

Primagen Dried Fluid Spot Technology for Viral Load Measurement 

MICHEL DE BAAR, AMSTERDAM, NED 

Evaluation of the Trugene GP41HIV-1 Genotyping Kit (Bayer) in Comparison 

with ANRS' Recommended Method 

JEAN-DOMINIQUE POVEDA, CERGY PONTOISE, FRA 

Mutations and Polymorphisms in the gp41 of the HIV-1 from T20 Naive 

Patients Receiving HAART 

CARLA TEIXEIRA, SÃO PAULO CITY, BRA 



• PP 2.7 

• PP 2.8 

• PP 2.9 

• PP 2.10 

• PP 2.11 

• PP 2.12 

• PP 2.13 

• PP 2.14 

• PP 2.15 

• PP 2.16 

• PP 2.17 

• PP 2.18 

Development of the Oligonucleotide Ligation Assay for the Detection of the 

M184V Mutation Associated with Resistance to Lamivudine in HIV-2 

SABELLE JALLOW, BANJUL, GAM 

Differences in the Phenotypic Profile of T Cell Subsets between Long Term 

Asymptomatic HIV and HIV Treated Patients in Virological Success could 

Contribute to Delay the Disease Progression 

CORINE BRUNET, MARSEILLE, FRA 

Immune Restoration under HAART in Patients Chronically Infected with HIV-1: 

Diversity of HIV Avidity and T, B and NK Immune Responses 

HÉLÈNE LE GUILLOU-GUILLEMETTE, ANGERS, FRA 

Biochemical Characterization of Mycobacterial Phosphoglucose Isomerase 

and its Mutants 

DIVYA MATHUR, NEW DELHI, IND 

Whatman FTA Cards, Designed for Collection, Transport, Archiving and 

Isolation of Nucleic Acids at Room Temperature, Inactivate Human 

Immunodeficiency Virus Type 1 (HIV-1) and BVDV (Model Virus for Human 

Hepatitis C Virus) 

OKSANA PENEZINA, SANFORD, USA 

Cellular Immune Response to Cryptosporidium Parvum in Cryptosporidium 

HIV Co-infected Patients 

KIRTI KAUSHIK, CHANDIGARH, IND 

Assessing the Contribution of CD8+ T Cells among TB Case-contact 

Cohort using Fresh Ex-Vivo Elispot Readouts 

LUGOS MOSES, BANJUL, GAM 

CD4 Independent Transmission of HIV 

ATMARAM BANDIVDEKAR, MUMBAI, IND 

Correlation between Circulating Viral Load and HIV-1 Detection in the Sperm 

of HIV-1 Positive Patients Consulting for Medically Assisted Procreation 

EMMANUELLE MOENS, BRUXELLES, BEL 

Possible 'Suicide Inhibition' by Peptide Oligomeres of HIV-1 Protease 

Inhibitors 

HANS J. SCHRAMM, MÜNCHEN, GER 

Interface Targeting Peptides as Inhibitors of HIV-1 Protease 


Inhibition of HIV Protease by Triterpene-Amino Acid Conjugates 




• PP 2.19 

• PP 2.20 

• PP 2.21 

HIV-1 Gene Expression: lessons from provirus and non-integrated DNA 

YUNTAO WU, MANASSAS, USA 

Inhibitory Activity and Protein Profile Characterization of Supernatant from 

Placental Macrophages. 

KATIA E. GARCIA-CRESPO, SAN JUAN, PUR 

Vesical Cancer and Papillomavirus : Homology between bovine 

Papillomavirus type 2 (BPV-2) E6 and mdm2 oncogene 

ADRIEN CAPRANI, PARIS, FRA 

Track III: HIV Clinical Science 

• PP 3.1 

• PP 3.2 

• PP 3.3 

• PP 3.4 

• PP 3.5 

The Presence of HIV/AIDS in an Older Adult Population 

BONNIE HATCHETT, MONROE, USA 

Is Age a Complicating Factor for Patients with Persistent Low Level Viremia? 

TOBY DYNER, SAN FRANCISCO, USA 

Opportunistic Infections Associated to a Late, First Diagnosis of AIDS 

Paradoxical increase of frequency at the time of highly active antiretroviral 

therapy (HAART) 


Reversible HIV Associated Encephalomyelitis Successfully Treated with 

HAART 

CHRISTOPHE RAPP, SAINT-MANDÉ, FRA 

Clinical and Bacteriological Features AIDS-related Mycobacterium Kansasii 

and Mycobacterium Xenopi Infection: a thirteen-year follow-up 


• PP 3.6 Mycobacterium ulcerans Cutaneous Infection (Buruli ulcer) : 

an emerging cause of immune restoration inflammation syndrom in african 

HIV-infected patients 


• PP 3.7 

• PP 3.8 

• PP 3.9 

Functional Limitation of Mycobacterium ulcerans Cutaneous Infections 

(Buruli ulcer): usefulness of a functional limitation score 


A Clinical Study of 60 Patients Of Multidrug Resistant Tuberculosis in 

Mumbai, India 

MOHAMMAD KHALID, MUMBAI, IND 

HIV and Tuberculosis: Partners in Crime 

JANAK MANIAR, MUMBAI, IND 



• PP 3.10 

• PP 3.11 

• PP 3.12 

• PP 3.13 

• PP 3.14 

• PP 3.15 

• PP 3.16 

• PP 3.17 

Mycological Findings from HIV-positive Children and Adults in Nairobi, Kenya 

OLGA MUKASIA MASHEDI, NAIROBI, KEN 

Clinicopathological Comparison of Tuberculous and Cryptococcal Meningitis 

Presenting to a Tertiary Care Hospital in Pakistan 

ARSHAD IQBAL, KARACHI, PAK 

Tuberculous Meningitis in HIV-infected Patients of the Province of 

Castellon, Spain 

BERNARDINO ROCA, CASTELLON, ESP 

Crohn's Disease Onset in a HIV/HCV Co-infected Woman Taking Pegylated 

Interferon plus Ribavirin 

MARCO BONGIOVANNI, MILANO, ITA 

HIV-associated Fungal Opportunism in the HAART Era. Trend of frequency, 

according to Protease Inhibitor administration 


Ocular Manifestations Occurred in Decline of HAART, concerning 4 observations 

SERGE EHOLIÉ, ABIDJAN, CIV 

Neurophysiological and Neurometabolic Characteristics of Patients under 

HAART with Cognitive Complaint 

V. FRIXON-MARIN, MARSEILLE, FRA 

Bladder Carcinoma Observed in HIV-infected Patients. An infrequent, 

but challenging finding 


• PP 3.18 Important Cutaneous Reaction during Enfuvirtide (Fuzeon ® ): 

an 8 cases report 

CORINE BRUNET, MARSEILLE, FRA 

• PP 3.19 

• PP 3.20 

• PP 3.21 

Increasing Concerns related to Gynecomastia among HIV-infected Patients 

Treated with Highly Active Antiretroviral Therapy (HAART). Epidemiological 

and clinical correlates, and startpoints for pathogenetic investigation 


Renal Function Tests and Blood Electrolytes before and after Atazanavir 

BERNARDINO ROCA, CASTELLON, ESP 

Glucose Intolerance and Insulin-resistance Found in HIV-infected Subjects 

During Their anti-HIV Protease Inhibitor Treatment: a prospective, randomized 

comparison study of three oral hypoglycemic drugs 




• PP 3.22 

• PP 3.23 

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• PP 3.26 

• PP 3.27 

• PP 3.28 

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• PP 3.30 

• PP 3.31 

• PP 3.32 

Multiple Subcutaneous Lipomatosis Prospectically Observed in Patients 

Receiving Highly Active Antiretroviral Therapy (HAART). Possible links with 

concurrent metabolic abnormalities, and pathogenetic insights 


Proviral DNA and Plasma Viral RNA Resistance Mutations in HIV1 Naive 

Patients 

BENOÎT KABAMBA MUKADI, BRUXELLES, BEL 

Elevated Serum Lactic Acid Levels During Highly Active Antiretroviral 

Therapy (HAART). Frequency, possible pathogenetic causes, and potential 

clinical significance 


Frequency, Monitoring, Clinical Significance, Treatment, and Prevention 

Determinants of Pancreatic Toxicity in the Era of Highly Active Antiretroviral 

Therapy (HAART) 


Invasive Candidiasis and Cryptococcosis Disclosed Concurrently in AIDS 

Presenters 


HIV-positive Cases as Part of Viral Complications after Renal 

Allotransplantation 

KRASSIMIR METODIEV, VARNA, BUL 

Successful Treatment of AIDS-associated Cryptococcus neoformans 

Meningitis, Apparently Prompting the Emergence of Amphotericin B-resistant 

Cryptococcus laurentii Central Nervous System Infection 


The Effects of a Supervised Exercise Programme on Self-efficacy, 

Cardiovascular Fitness and Quality of Life in HIV/AIDS 

SOULA FILLIPAS, PRAHRAN, AUS 

Osteopenia and Osteoporosis in HIV-infected Patients Treated with 

Antiretroviral Therapy. A relationship with male gender and protease inhibitor 

administration 


Prevalence of Depression among AIDS Patients on Antiretroviral Therapy in 

Two Tertiary Care Hospitals of Delhi, India 

SHASHI KANT, NEW DELHI, IND 

Clinical Outcomes in HIV Positive Patients after Dentoalveolar Surgery 

SHETTY KISHORE, HOUSTON, USA 



• PP 3.33 

• PP 3.34 

• PP 3.35 

• PP 3.36 

• PP 3.37 

• PP 3.38 

• PP 3.39 

Rhinopharyngeal Carcinoma with a Concomitant, Local Lymphoproliferative 

Disorder, both Related to an Underlying, Concurrent HIV and Epstein-Barr 

Virus Infection 


Fatal Disseminated HIV-associated Prostatic Adenocarcinoma Presenting 

with Non-specific Features 


Large Vessel Damage due to Accelerated Atherosclerosis Observed during 

HIV Disease. Life-threatening rupture of an aortic aneurism in an HIVinfected 

patient 


Impact of Syphilis Infection on HIV Viral Load and CD4 cell Counts in 

HIV-infected Patients 

ROSARIO PALACIOS, MÁLAGA, ESP 

No Interference between Syphilis and Virological and Immunological Markers 

of HIV Disease 


Follow up Study - Oral Candida Flora from Brazilian HIV 1-Infected Children 

in the HAART Era 

NADJA MELO, SWANSEA, GBR 

Faecal Flora, Diarrhoea Associated with Protease Inhibitors in HIV-infected 

Patients 

FRANCINE DE SALVADOR-GUILLOUËT, NICE, FRA 

Track IV: HIV Therapy 

• PP 4.1 

• PP 4.2 

• PP 4.3 

• PP 4.4 

Evaluation of a Triple Therapy Associating 2 NRTI + Efavirenz Versus 2 NRTI 

+ Indinavir in HIV-1 Positive Patients with less than 100 CD4/mm3 at Initiation 

ARISTOPHANE TANON, ABIDJAN, CIV 

Triple Therapy Adherence in HIV Infected Adults in Abidjan, March to 

September 2002 

ARISTOPHANE TANON, ABIDJAN, CIv 

Patterns and Predictors of Adherence to Antiretroviral Medications in Older 

Adults Living with HIV/AIDS in the United States 

BERNADETTE DAVANTES HECKMAN, NEW HAVEN, USA 

Experience with ART Adherence Counselling at Muhimbili National Hospital, 

Dar Es Salaam, Tanzania 

MILLEN RINGO, DAR ES SALAAM, TAN 



• PP 4.5 

• PP 4.6 

A Prospective Study of Antiretroviral Drug Adherence in HIV-Infected Patients 

in Oman 

SAID HAMED SAID AL DHAHRY, MUSCAT, OMN 

Impact of Free and Universal Access to Antiretroviral Treatment on the 

Survival among Brazilian Children with AIDS 

LUIZA HARUNARI MATIDA, SAO PAULO, BRA 

• PP 4.7 Telephone-Based Coping Improvement Group Intervention for Persons 50 

Years of Age or Older Living with HIV/AIDS in the United States 

TIMOTHY G. HECKMAN, ATHENS, USA 

• PP 4.8 

• PP 4.9 

Management of Nutrition-related Symptoms among People Living with 

HIV/AIDS under Antiretroviral Therapy 

ADAMA NDIR, DAKAR, SEN 

The Significantly Different Profile on Lipid Metabolism and its Correlates, 

caused by Efavirenz Compared with Nevirapine 


• PP 4.10 Evolution of HIV1 infected Patient ProfileTreated by Enfuvirtide (Fuzeon ® ) 

ISABELLE POIZOT-MARTIN, MARSEILLE, FRA 

• PP 4.11 

• PP 4.12 

• PP 4.13 

• PP 4.14 

• PP 4.15 

• PP 4.16 

Self-evaluation Investigation of Patients Treated by Antiretroviral Therapy 

BÉNÉDICTE COUREAU, MARSEILLE, FRA 

Significant Modification of Administrative Re-imbursement Facilities of all 

Lipid-Lowering Drugs in Italy. No consideration of HIV-infected patients with 

HAART-related dyslipidemia, who loss their right to a re-imbursed access to 

statins, fibrates, and omega-3 derivatives 


Treatment of Kaposi's Sarcoma by Peginterferon alfa-2a 

JEAN-LUC DELASSUS, AULNAY SOUS BOIS, FRA 

Immune Markers of HIV Disease Progression are not Modified by long-term 

Statin Administration, when considering HIV-infected Dyslipidemic Patients 

Treated with a Steadily, Virologically Effective HAART regimen. A prospective 

study, controlled versus fibrate administration, or a dietary/exercise program 


Pharmacokinetic Interaction Between the HIV Protease inhibitors TMC114 

and Indinavir, in the Presence of low-dose ritonavir 

VANITHA SEKAR, YARDLEY, USA 

Effects of Demographic Factors on Trough Lopinavir and Ritonavir Plasma 

Concentrations in HIV- infected Patients Treated with Kaletra 

JEAN-MARIE POIRIE, PARIS, FRA 



• PP 4.17 

• PP 4.18 

• PP 4.19 

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• PP 4.21 

• PP 4.22 

• PP 4.23 

• PP 4.24 

• PP 4.25 

• PP 4.26 

Human Immunodeficiency Virus type 1 (HIV-1) Proviral Load in Patients in 

Structured Treatment Interruption 

SHIRLEY KOMNINAKIS, SÃO PAULO CITY, BRA 

Rosuvastatin Administration for Protease Inhibitor-related Hyperlipidemia, 

with a Predominant Hypercholesterolemic Component 


Much More Sure than 2 Years Ago: The CD4-Stabilizing Effect of 5 mg 

Prednisolone Daily in HIV-Patients without HAART 

ALBRECHT ULMER, STUTTGART, GER 

Arising Questions on a Cost-effectiveness and Pharmacoeconomic 

Investigation Focused on Diagnosis, Management and Prevention of 

Osteopenia and Osteoporosis in the Setting of HIV Disease Treated with 

HAART 


No Evidence of Reduced Viro-immunological Response in HIV+ Patients 

Previously Naïve to Antiretroviral Treatment Carrying non B or B HIV-1 

Subtypes 

MARIA CRISTINA UCCELLI, BRESCIA, ITA 

The Incidence and Reasons of the Premature Giving up of Abacavir in HIV 

Patients within 2 Months Following the Treatment Setting-up 

NADINE FOUCHER, BORDEAUX, FRA 

The Increased Liver Toxicity of Nevirapine over Efavirenz does not Depend 

on the Female Gender, and an Initially Elevated CD4+ Lymphocyte Count, in 

a Single-centre Comparative Study with Efavirenz Conducted on 720 Overall 

Patients 


Early Aplasia Resulting from Interaction Between Antiretroviral Therapy and 

Vinblastine in a Patient with HIV-associated Hodgkin's Disease 

JACQUES REYNES, MONTPELLIER, FRA 

Rapid Oral Desensitization to Abacavir in Case of Probable Hypersensitivity 

ALBRECHT ULMER, STUTTGART, GER 

Cell-cycle Independent Antiretroviral Therapy: combination of nevirapine, 

emtricitabine, and tenofovir 

CHARLES DAVIS, BALTIMORE, USA 



Track V: Hepatitis Viruses 

• PP 5.1 

• PP 5.2 

• PP 5.3 

• PP 5.4 

• PP 5.5 

• PP 5.6 

• PP 5.7 

• PP 5.8 

• PP 5.9 

Rational Design of HCV Antigens to Contend with Diversity and Optimize 

T cell Reactivity 

Karina Yusim, Boston, usa 

Detection of HIV/HCV Co-infection Markers in Blood and Saliva 

ALEXANDER OLSHANSKIY, MOSCOW, RUS 

Immune Restoration Levels Under Highly Active Antiretroviral Regimen, in 

Patients Co-infected with HIV and HCV 


The Impact of Hepatitis on Health-related Quality of Life and Medical 

Expenditures in the United States 

PATRICK SULLIVAN, DENVER, USA 

Fulminant Candida albicans Peritonitis and Ascites in a HIV-HCV 

Co-infected Patient, Possibly Prompted by a Prolonged Self-administration 

of Nimesulide 


Extrahepatic Manifestations of HCV: an experience from endemic country 

ALAA SABRY, MANSOURA, EGY 

Chronic Hepatitic C-prompted Peglylated Interferon (IFN) plus Ribavirin 

Therapy and Re-activated, Acute, Serious Lung Tuberculosis 


Management of Chronic Hepatitis C with Pegylated Interferon and Ribavirin 

in a Prison Setting 


Chronic HBV Infection Associated with Opisthorchiasis: efficacy of antiviral 

therapy 

OLGA KULAGINA, KEMEROVO, RUS 

Track VI: Emerging Infectious Diseases 

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• PP 6.2 

Air Evacuation of Patients with High Infectious Disease under Biosafety 

Containment 

MARCO LASTILLA, ROMA, ITA 

Broadly Protective Immunity against Influenza A using a Synthetic Vaccine 

FRANSICO DIAZ-MITOMA, OTTAWA, CAN 



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Imported Chikungunya Related Chronic Poly-arthritis : 2 cases 


Chikungunya Arthritis Sequelae: Molecular homology between Lyme arthritis 

Borrelia Burgdorferi, LFA-1a and Chikungunya virus gp1 

MKG TRAN, PARIS, FRA 

Experimental Determination of the Infectivity of Avian influenza Virus 

Aerosols 

ALEXANDER SAFATOV, KOLTSOVO, RUS 

Tick-borne-lymphadenopathy (TIBOLA) : an emerging infectious disease 

in France 


Emerging Arboviruses in Turin Province 

AGOSTINO PUGLIESE, TURIN, ITA 

Re-emerging Tuberculosis. Are There Significant Correlations with HIV 

Infection and Other Risk Factors, Between Residents and Immigrants? 


Ocular Loa Loa Infection in an Italian Restricted Man 

MARCO BONGIOVANNI, MILANO, ITA 

Complicated Listeria monocytogenes Central Nervous System (CNS) 

Infection in an Otherwise Healthy Host: favourable response to linezolid, 

notwithstanding early myelotoxicity 


Prevalence of Carriers of Methicillin Resistance Staphylococcusaureus 

(MRSA) in 100 Staff of Shahid Beheshti Hospital of Kashan (Iran) 

AHMAD KHORSHIDI, KASHAN, IRN 

Severe, Extensive, and Difficult-to-eradicate Strongylodies stercoralis 

Infection Probably Supported by an Underlying Sjogren Syndrome Requiring 

Long-term Steroid Treatment 


Evaluation of the Prevalence of Urinary Tract Infection and Determination of 

Antibiotic Sensitivity and Resistance Pattern in the Hospitalized and out 

Patients Referred to Shahid Beheshti Hospital of Kashan -Iran 

AHMAD KHORSHIDI, KASHAN, IRAN 

Primary Cytomegalovirus (CMV) Infection with Symptomatic Course in 

Otherwise Healthy Adults: increased incidence, or improved laboratory 

facilities? 




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Assessment of Need of Inpatient Hospitalization at an Italian Infectious 

Disease Division 

ROBERTO MANFREDI, BOLOGNA, IITA 

Isolation of Corynebacterium spp. Organisms in Different Clinical Settings of 

a Large Teaching Hospital. Focus on intensive care units 


Community-acquired Septicemic Pneumonia Caused by a Multiresistant 

Staphylococcus aureus Strain, Resulting in Multiple Organ Involvement 

Exacerbated by Extensive Immune Activation 


Severe, Pulmonary Atypical Mycobacteriosis in a Patient Suffering from 

Decompensated Liver Cirrhosis, but Intolerant to Multiple Therapeutic 

Attempts. Spontaneous resolution in absence of relapses after a three-year 

follow-up 


Multiple Sclerosis Managed without Immunosuppressive Therapy. 

Detection of pulmonary zigomycosis as an indolent fungal complication 


Severe Mediastinal Tuberculosis Complicated by Main Bronchial and 

Thoracic Aortic Compression and Long-term Esophageal Fistulization, in a 

Patient with Negative History and Pulmonary Signs and Symptoms of 

Tuberculosis 


A Serious Staphylococcal Knee and Soft Tissue Infection Responsive to 

Linezolid only, after Failure of all Other Therapeutic Attempts. Discrepancy 

between favorable in vitro bacteriological testing and a worsening clinical 

course 


Expression of Fused B Subunit of Heat-labile Enterotoxin and a Linear 

Epitope of Colonization Factor Antigen I of Escherichia coli 

NADER SHAHROKHI, TEHRAN, IRN 

Comparison between Secretory Leukocytic Protease Inhibitor and Reactive 

Nitrogen Intermediates Levels in Cervicovaginal Secretions from 

symptomatic and Asymptomatic Trichomoniasis Egyptian Patients 

HAMDAN I. AL-MOHAMMED, ISMAILIA, EGY 

Controversies in the Antimycotic Management of Candida albicans 

Panophthalmitis: an exemplary case report and discussion of guidelines of 

antifungal chemotherapy 


Real- Time PCR and Flow Cytometry for Detection of Cyclospora Oocysts 

from Fecal Samples of Gastrointestinal Symptomatic and Asymptomatic 

Patients 

EMAN M. HUSSEIN, SMAILIA, EGY 


OP 1.1 

The role of care givers 

Dr Denis Lacoste 

Praticien Hospitalier CHU de Bordeaux 

Société Française de Lutte Contre le SIDA 

More than ever health care workers must remain mobilized and involved in the fight 

against HIV in a global way. History showed us, with the discovery of this so particular 

pathology, the impact that could have in practice such a care, with this considerable 

change of the relationship between patients and care workers which could be observed. 

In any care setting, the patient is the center of the organization. The French Networks of 

Care are built on this scheme. The role of associations which will be considered 

thereafter was a determining element of these changes. 

ABSTRACTS 

It is not adequate here to come back to the past but to lean on what it is today and look 

forward... 

In the Northern countries, and specially in France, since the advent of Haart and the 

improvement of the infection's pronostic, after the euphoria, a demobilization was 

perceived which was first of all marked on a political level, then the media, with that notion 

of the evolution from a subacute disease towards a chronic pathology. The "vulgarization" 

with his perverse effects in the forefront of which an obvious demobilization of many 

actors, the absence or the difficulty to find new energies to take over the very implied 

actors from the beginning. A debate takes place, at the present time, about the question: 

"does the HIV remain, or must it remain, an exception in the care?". In France, this 

medical care remains centered on the hospital and one notes a weak activity of the 

private sector in spite of the existence of networks still implied in this pathology, whether 

it is in a mono or plurithematic way. However we are thoroughly convinced, and this can 

be checked every day in the practice, that it is not time to give away but on the contrary 

vigilance should be maintained. Epidemiology shows clearly that the HIV epidemic, 

including in the Northern countries, is far from being extinct (the data show it year by year); 

the relative failure of the prevention policy in the field of sexuality, the progressing 

precariousness, the migratory phenomena bring moreover specificities in terms of 

culture, pathology and adapted care. The comorbidities, the side effects of the treatments, 

increase the specificities of such a care... 

One awaits from professionals of HIV care to be qualified, not only in health care, but also 

in practice of the prevention. This for the patients themselves, and towards the general 

population, prevention which concerns of course the transmission of HIV, prevention of 

therapeutic failures by an assiduous work in terms of support of adherence and 

therapeutic education. Implication including psychosocial care of the HIV patients to 

facilitate the access to the care or to restore it in case of break. 

We assume in France at the present time a reform of the organization of HIV care with the 

creation of Regional Coordinations (COREVIH), which must relay in 2006-2007 the 

existing network of the CISIH (Centre d'Information et de Soin de l'Immunodéficience 

Humaine). It is the occasion for health care workers to think about their organization, with 

new missions, in bond with associations of patients and the State Services. Of course, the 

question of the means (which become more difficult to obtain), arises in France because 

of this reorganization. 


The hospital reform in progress may be to a great extent a break for many innovating 

actions which had to be carried out in the past... Therefore, there is today a considerable 

risk, to see certain professionals moving away from the field of the HIV. It is, as already 

said, difficult to mobilize new energies. We are in a transitional period which makes that 

the "old hands" must do their best to relay their experiment and thus to teach and share 

their knowledge with younger health care workers. 

About the Southern countries, the role of associations of patients is particularly important 

in terms of mobilization and education. A long-term action must be completed there taking 

into account the importance of HIV care in these countries where finally one perceives that 

the access to Haart is not any more the challenge that it could be in a recent past. 

Inequalities still too obvious in certain areas must be withdrawn step by step. Let us insist 

on the irreplaceable character of the NORTH-SOUTH exchanges within individual 

initiatives of professionals or within international programs, as ESTHER program with 

partnerships defined between hospitals or with actions carried out within the SIDACTION 

with associative support but also financing therapeutic programs. There is important 

programs carried out by other Non Governmental Organizations such as "Médecins Sans 

Frontières", "Médecins du Monde" and many others with an important role of expertise. 

The existence of an association of health care workers like the Société Française de Lutte 

Contre le SIDA (SFLS), is an opportunity to have a personal reflexive attitude or more 

largely inter professional exchanges. 

In conclusion, the history of AIDS was marked by the advent of Haart, one of the most 

important events, but it is quite clear that the health care workers, whatever their 

professional category, must more than ever imply themselves, to progress technically and 

ethically. On all the fields of HIV care, a multipartite working way should be with 

associations of patients, the politicians, without forgetting cultural and religious 

dimensions. 


OP 1.2 

The patient is our goal 

Do we still need anti-AIDS associations? 

Christian Saoût, AIDES Paris - France 

The answer to this question is incontrovertibly, yes! 

It is not enough to insist on the fact, however, without giving the reasons. These are as 

follows. 

ABSTRACTS 

1) There are still huge questions to be answered in the fight against AIDS, and the way 

health systems are developing in the North, as in the South, it is not likely that people's 

needs will be satisfied without their involvement. How to organise a social life when on 

long-term treatment? How to change the scale of prevention in both North and South 

when faced with 'pockets' of the population kept far removed from information on 

prevention and the necessary tools? 

2) In addition to questions of public health there are societal issues. People living with 

HIV-AIDS are still far from being accepted by their immediate entourage (partner, family, 

friends) and in wider circles (workplace, leisure, society). A recent survey for AIDES 

(AIDES & TOI, 2005) bears dramatic witness. The place of people living with HIV-AIDS is 

still far from being acknowledged in our societies in the North, as well as those in the 

South. 

3) Even beyond AIDS, anti-AIDS activists are needed. Our forms of activism still remain a 

model for other healthcare initiatives which we must strive to pass on, both in the North 

and the South. In the North to reinforce the reform of our system of treatment. In the South 

to respond to the expectations of countries currently reorganising their system of 

treatment, both in the public and private sector. 

In these three aspects, the role and the position of patients are essential, and in a world 

of experts their contribution can act as a powerful spur for action. 


OP 1.3 

Public Health and Social Science in Clinical Research: 

the interest of a multidisciplinary approach 

France Lert (INSERM, U687, Saint Maurice, France) 

Since the advent of HAART ten years ago, HIV infection has turned from a fatal disease 

to a chronic condition hitting individuals in their early adulthood and for their whole 

lifespan. However survival of people living with HIV depends directly upon accessibility to 

care and to effective treatment, upon social and economic support to face the burden of 

a lifelong disease, upon accurate response to special needs of patients who do not 

participate in or are excluded from / the mainstream of society : undocumented migrants, 

illegal drug users, homosexual males. We all know that early diagnosis of HIV infection, 

comprehensive approach of care, availability of the full range of ARV medicines, provision 

of emotional and social support from the society and from significant others allow patients 

to live long with a rather good quality of life. Clinical Thus research activities aim at 

identifying and understanding barriers to effective care, to measure failure in achieving the 

best possible duration and quality of life, to assess inequalities and to search new 

strategies and tools to enhance treatment effectiveness. Since the early period of the 

AIDS era, activists have urged the scientific community to mobilise the whole range of 

disciplines, from basic sciences to social disciplines, to counter HIV AIDS pandemics both 

in resource-rich and -poor settings. To date the normalisation of HIV social issues has not 

shattered the uncommon multidisciplinary approach of HIV research. Examples will be 

shown of research outcomes showing the interest of various approaches to design 

effective interventions and to revise care provision. 


OP 1.4 

An anthropological approach of HIV/AIDS 

Stéphanie Mulot, Anthropologist, Maître de conférences, Université Toulouse le Mirail, 

stephanie.mulot@univ-tlse2.fr 

The anthropological approach of the doctor-patient relationship and of PLHIV lifes aims at 

understanding what is beneficial or not for patients'care and treatments success. With a 

qualitative analysis, we try to explain how the intersubjective construction of care also 

depends on many representations, believes, fears, categorisations, acting between 

patients et carers, maybe more than on treatments themselves. We aim at showing that 

the hospital care givers have to face a need of social support from PLHIV in their work of 

identity reconstruction, after the HIV/AIDS diagnostic. It is particularly true in case of an 

invisible epidemic, when cultural pression are strong and activist associations are weak, 

as for example in the French West Indies. 

ABSTRACTS 


OP 2.1 

Research Priorities in HIV : Epidemiology 

Amanda Mocroft, HIV Research Unit, Dept Primary Care and Population Sciences, Royal 

Free and University College Medical School, Rowland Hill St, London, NW3 2PF. UK. 

The widespread introduction of combination antiretroviral therapy (cART) to Europe during 

1996 has led to a remarkable decline in new AIDS defining illnesses and deaths. Clinical 

trials of new antiretroviral therapies concentrate on the short term virologic or 

immunologic response to cART, and there are few trials considering longer-term 

outcomes. Typically, clinical progression is now considered within the setting of large, 

often collaborative, observational studies, which can introduce considerable bias when 

comparing antiretrovirals. This is because there will be both unmeasured and unknown 

confounders influencing the choice of treatment, which may affect the outcome. 

Observational studies have however contributed enormously to research, have provided 

important input into HIV treatment guidelines, and have been used to both help in the 

design and running of randomised clinical trials. 

There remain many questions to be answered in the cART era, and these can be 

focussed into the continuing morbidity and mortality observed, the development of 

resistance and adverse events. Will the efficacy of cART continue in all patients, and if not, 

what determines why some patients do not seem to experience the same benefits from 

cART as others? Clearly, patients who die in the cART era die from a much wider range 

of causes than seen before, and the epidemiology of deaths in HIV has become much 

more complicated. cART cannot reduce the risk of deaths which are truly unrelated to HIV 

infection, but it is uncertain to what extent causes of death are related to HIV or 

associated immunodeficiency. Serious adverse events, such as pancreatitis or chronic 

kidney disease, may only become apparent after the long-term follow-up of a large 

number of patients, which is not normally possible within the setting of a randomised 

clinical trial. In such circumstances, well conducted observational studies can provide 

important information of both the expected frequency of serious adverse events, and 

determine which patient groups have the greatest risk of such toxicities. There is an 

increasing group of patients who have been exposed to all available classes of 

antiretrovirals, have multi-drug resistance and have failed all regimens. These patients are 

typically not included in randomised trials, which concentrate on antiretroviral naïve 

patients with the best chance of virologic success but have the greatest risk of clinical 

progression. Is this patient group likely to continue increasing, and if so, which group of 

patients are at greatest risk, and how likely are they to develop AIDS or die? 


OP 2.2 

Research priorities In Virology 

Luc Perrin, MD, laboratory of virology, Geneva University Hospital, Geneva , 

Switzerland. 

This overview will start with the issue of viral load testing in resource limited settings(RLS). 

In most area it is just not available and there only 2 lines of predefined HAART available. 

Cross-resistance for the drugs of second line increases over length of treatment on first 

line in patients with virological failure. In particular, the long term treatment with first line 

therapy in women of reproductive age will likely results, in those with partial response, to 

transmission of drug resistant virus in their new-borns. Implementation of viral load in RLS 

would likely be cost effective soon but ideally would require new assays less dependant 

of cold chain and cheaper. 

There are a number a number of issues concerning both developed countries and RLS 

including increased viral diversity, potential changes in pathogenicity of HIV, resistance 

testing and mechanisms of resistance. 

There are at least 4 main more basic areas of priority for virology 

- Viral replication and identification of new targets for drug development. Indeed the 

potential to develop new drugs against the same target is somewhat limited whereas no 

cross-reactivity is observed against new targets. Also better knowledge of HIV accessory 

genes may lead to major unexpected progresses as shown recently for vif. 

- The viral reservoir, initial size and HIV , dynamics on treatment, possibility to "purge" the 

provirus. 

- Host genetics and resistance to HIV infection, impact on disease progression and 

pharmacogenetic. Large international programs are focusing on these issues. Patients 

care may benefit indirectly from new findings in particular for pharmacogenetic. One can 

not exclude more dramatic development: several years ago it has been shown that 

homozygous deletion within CCR5, the second receptor confers full protection for HIV 

infection. Development in virology/molecular biology might allow in the future to 

selectively block the CCR5 gene and this might be the strategy of choice in areas with 

high HIV prevalence. 

Vaccines: both therapeutic and prophylactic vaccines are developed by individual groups 

and consortium exploring a large numbers of diversified approaches. This would be the 

ideal tool to control HIV worldwide but will require years of investigations and clinical trials. 

ABSTRACTS 


OP 2.3 

Research Priorities In HIV Immunology ? 

Marie-Lise GOUGEON, 

Unité Immunité Antivirale, Biothérapie et Vaccins, Institut Pasteur, Paris 

The pathogenic and physiologic processes leading to AIDS remain a conundrum. Upon 

transmission to a new host, HIV targets effector memory T cells, resulting in acute, 

massive depletion of these cells from mucosal sites, including gut. Does this early 

depletion compromise the regenerative capacity of immune cells? Mucosal depletion is 

closely followed by the onset of generalized immune activation. What is the cause of 

chronic immune activation? Does it reflect a homeostatic response, or activation by 

mucosal antigens, or "bystander effects" of innate and adaptive immune response to HIV 

replication, involving cytokines, self-antigens and foreign microorganisms? Because 

persistent activation progressively disrupts the functional organization of the immune 

system, reducing its regenerative capacity and facilitating viral evolution that leads to 

AIDS, it is important to resolve this issue and to design strategies to target host 

mechanisms that contribute to loss of immune functions. 

The characterization of innate immune cells and the way they control HIV infection is 

another important research area. Natural killer (NK) cells can contribute to the host 

immune response to HIV infection through cytolytic and non cytolytic mechanisms, and 

genetic and functional studies of exposed, uninfected individuals indicate a protective role 

for NK cells in the early stage of HIV infection. Interaction with dendritic cells (DC) and 

priming for the adaptive immune response is another important function of NK cells. 

HIV induces several alterations in NK-cell phenotype and function in vitro and in vivo, but 

further research is warranted to determine the role of NK cells in the control of HIV 

viraemia, in the development of mucosal immunity and in protection against mucosal 

infection, in order to specifically target NK cells with new molecules that would activate 

them to lyse HIV-infected target cells in vivo. With regard to vaccine development, further 

delineation of the immune correlates of protection during natural infection and after 

vaccination is a fundamental task. Recent data suggest that the effectiveness of virusspecific 

immune responses is not exclusively based on the quantity but rather on the 

quality of CD4 and CD8 T cells. Indeed, the control of virus replication by HIV-specific cell 

mediated immunity is suggested by several observations i.e. virus-specific CD8 T cells are 

detected in individuals who were exposed to HIV but remained uninfected, depletion of 

CD8 T cells results in a loss of virus control in monkeys infected with SIV, the 

preservation of HIV-specific helper CD4 T cell responses is associated with virus control 

after interruption of antiviral therapy during primary infection, HIV-specific CD4 and CD8 

responses are preserved in LTNP and the memory T cell responses are qualitatively 

similar to the EBV and CMV-specific immune responses that control both infections. 

Nevertheless, definitive experimental evidence that certain types of immune response are 

indeed immune correlates of protection are needed before current candidate vaccines can 

be moved into large efficacy trials. Concerning humoral immunity, it is still unclear whether 

neutralizing antibodies have a substantial role in the control of chronic steady-state 

viraemia, but their limited effect may be related to the very rapid evolution of the virus and 

the selection of variants that are resistant to the most broadly neutralizing antibodies. 

A number of questions have to be solved: what is the impact of HIV-induced B cell 

maturation defects on the viral escape from neutralizing antibodies? Is it possible to 

design immunogens capable of inducing protective neutralizing antibodies by active 

vaccination ? how to induce high titers of neutralizing antibodies? Determining the 

correlates of immune protection provides insight the mechanisms of protection, although 

it does not prove cause and effect. In addition, the correlates of protection involved in 

preventing disease progression during natural infection with HIV do not necessarily reflect 

those that would be protective in the presence of pre-existing vaccine-induced immunity. 

Therefore, more basic research is still needed to elucidate the mechanisms of immune 

control of HIV infection and the correlates of vaccine protection. 


OP 2.4 

Research Priorities in HIV/In Therapy 

No abstract available 

OP 3.1 

The outcome of Children HIV - Infected at the beginning of the epidemics 

Dr Albert Faye, Service de Pédiatrie Générale de l'Hôpital Robert Debré, Paris, France 

Very long term outcome of HIV-1 infected children is one of the major issue of pediatric 

AIDS epidemics. The positive impact of HAART and particularly of the early treatment in 

HIV infected infants has been demonstrated now in several observational studies. 

However this impact is counterbalanced by the potential long term side effects of the 

antiretroviral drugs. Lipodystrophy, and metabolic abnormalities such as high lipids and 

insulin levels has been described respectively in 24 and 42% of a longitudinal French 

cohort. Other metabolic abnormalities such as bone disorders with tenofovir and 

mitochondiopathy with nucleoside inhibitors are also of great concern in children. The 

virus itself could be also involved in long term cardiovascular complications in 

HIV-infected children with or without HAART. 

ABSTRACTS 

Few clinical and biological data are available for adolescents living with HIV infection since 

birth. Analysis of the subgroup of children and adolescents, still alive, born before 1993 

and whose most recent medical visit took place after 2002 was done in the French 

prospective perinatal cohort. Of the 592 infected children followed since birth, 171 (92 

boys and 79 girls), met the criteria for this analysis, with a median age at last visit of 14.5 

years (IQ: 13.0 ; 16.5 years). A history of CDC category C diagnosis was reported for 19% 

of the children. Most (92%) were initially treated with Zidovudine monotherapy. 

Subsequently, and at various ages, 87% of children received HAART (36% between the 

ages of 3 and 6 years). At last visit, 77% were receiving multitherapy, 19% received no 

ART and 4% were maintained on bitherapy. Sixty percent of the current HAART consisted 

of a combination of nucleoside analogs with boosted proteases inhibitors. The median 

CD4 T-cell percentage was 30% at first ART. It was 27% at last visit, with a minority of 

children having CD4 percentage below 15 (15%). The last median CD4 cell count was 

565/mm3. The last median viral load (VL) was 170 copies/mL. VL was below 400 cp/mL 

for 54 % of children, and over 100,000 cp/mL for 7% only. Thus, despite a long period of 

suboptimal antiretroviral treatment, most of the still alive young adolescents currently are 

in a good clinical, immunological and virological state. 

Finally, asymptomatic long term survivors (ALTS) are very few in children representing 

around 3% in the French Perinatal cohort after 12 years of follow up. These ALTS children 

have received either no antiretroviral drug or a monotherapy and have CD4 cell counts 

more than 15%. Understanding the mechanisms of such clinical and biological outcome 

is an important challenge in the long term pediatric HIV infection management. 


OP 3.2 

Interactions between HSV and HIV 

Dr Anna Maria Geretti 

MD, PhD 

Royal Free Hospital, London 

HSV-specific T-cell responses are reduced in HIV-1 infected persons compared with 

uninfected individuals. Impaired immunological control results in increased frequency of 

HSV reactivation and high levels of virus shedding, and can lead to the development of 

severe chronic mucocutaneous lesions poorly responsive to antiviral therapy. 

The potential impact of poorly controlled HSV replication is significant. In addition to the 

effects on HSV disease, frequent HSV reactivations have been shown to promote HIV-1 

replication and increase HIV-1 RNA levels in plasma, with implications for HIV-1 

transmission and disease progression. This presentation will review the epidemiology and 

natural history of HSV infection in HIV-1 positive persons and present data on the impact 

of HAART on the clinical expression of genital herpes and HSV-specific immune 

reconstitution. Published evidence indicates a high prevalence of HSV-1 and HSV-2 

infection among HIV-1 positive persons. In a cohort of 850 adults diagnosed HIV-1 

positive in London in 1986-2001, seroprevalence at the time of HIV-1 diagnosis was 88% 

(95% CI 86-91%) for HSV-1 and 63% (95% CI 60-66%) for HSV-2. Detection of HSV-2 

antibodies was associated with female gender, heterosexual risk group, black ethnicity, 

and older age. Over median 3 years of follow-up, HSV-2 seroincidence in the same cohort 

was 1.8 per 100 person-years (95% CI 0.8-2.8) and was associated with a diagnosis of 

other STDs, including HPV infection and gonorrhea. Underdiagnosis of genital herpes is 

common among both HIV-1 positive and HIV-1 negative individuals, in part reflecting the 

poor sensitivity of virus culture of mucocutaneous swabs used for HSV detection. 

Consistent with this hypothesis, a comparative study showed that the use of real-time 

PCR increased HSV detection in genital swabs by 71% relative to virus culture. In 

addition, HAART has a significant beneficial effect on the clinical expression of HSV 

infection. In a cohort of HIV-1 and HSV-2 seropositive patients, only 21% received a 

clinical diagnosis of genital herpes and this was more likely in persons who tested HIV-1 

positive before 1997 (adjusted OR 5.11; 95% CI 3.28-7.98) than in those diagnosed in 

later years. A prospective study of persons starting first-line HAART found that restoration 

of HSV-specific immunity occurred slowly and in parallel with raising CD4 counts. Over 

median 40 weeks of therapy, the number of spot forming cells measured in ELISPOT 

assays increased by 5.6 (95% CI 1.2-9.9) per month and by 21.3 (95% CI 13.8-28.7) per 

100 CD4 cells gained. Thus, persons starting HAART with a CD4 count around 200-250 

cells/mm3 require on average 33 months of virologically and immunologically successful 

therapy to restore HSV-specific CD4 T-cells responses to the levels observed in healthy 

donors. This provides a threshold for HSV-immune reconstitution that may assist with 

clinical management. 


OP 3.3 

Neurocognitive Impairment in the HAART Era 

Tozzi V, Balestra P, Vlassi C, Corpolongo A, Salvatori MF, Bellagamba R, Antinori A, 

Narciso P 

National Institute for Infectious Diseases "Lazzaro Spallanzani", Rome, Italy. 

There are three levels of HIV-related neurocognitive impairment (NCI): 1) Asymptomatic 

NCI, with no decline in everyday functioning, 2) Mild Neurocognitive Disorder (MND), with 

mild functional impairment, 3) HIV-dementia (HIV-D), with moderate to severe functional 

decline. Although there has been a decline in the incidence of HIV-D as presenting 

manifestation of AIDS, the overall prevalence of the HIV-related NCI might be increasing. 

In HIV-infected patients the lifetime prevalence of HIV-D is 5 to 10%, and the prevalence 

of MND is around 20% in patients with advanced diseases. Among general population 

HIV-D is the most common cause of dementia in persons age 25-40 years. 

Epidemiological studies indicate a change in risk factors for HIV-D. The CD4 cell count at 

diagnosis of HIV-D, being 50 to 100 in the pre-HAART era, has now significantly 

increased. New risk factors for HIV-related NCI have been identified: duration of HIV 

infection, HCV co-infection, lower nadir CD4 count. Moreover, as patients are living 

longer, they are now more exposed to other factors that could affect cognition like 

testosterone deficiency, aging, and increased cholesterol and triglyceride levels. HIV-D is 

a debilitating disorder, that negatively affects patient's ability to perform activities of daily 

living, quality of life, adherence to antiretroviral therapy, and survival. Before the 

introduction of HAART, HIV-associated NCI was recognized as an independent risk factor 

for death. We have recently shown that the HIV-associated NCI is associated with a 

significantly greater mortality even in patients receiving HAART and that, after adjustment 

for confounding variables, the increased risk of death for neurocognitively impaired 

patients persists only among patients with virological failure, while the survival probability 

of patients with durable virological suppression is not affected by NCI. The optimal 

treatment for HIV-D has not been established, but there are strong evidences HAART is 

effective in treating the cognitive impairment. In patients with HIV-D the primary goal of 

antiretroviral treatment is to achieve complete virological suppression both in plasma and 

in the CSF. It remains controversial whether a combination drugs with good CSF 

penetration is essential for an effective treatment of HIV-D. Although HAART can reverse 

HIV-D, a substantial proportion patients may continue to show a persistent NCI despite 

HAART. We have assess prevalence and predictors of persistent NCI despite long-term 

HAART. Our data indicate, that although HAART is associated with an improvement in 

cognitive abnormalities, the impairment may persist in more than fifty percent of patients 

despite more than 5 years of HAART. Positive HCV serology, lower education and 

greater impairment in measures exploring memory and concentration is associated with 

persistent NCI. At multivariable analysis the severity of neurocognitive impairment 

appears to be the strongest predictor of persistent NCI despite HAART. Our data indicate 

that HAART should be initiated as soon as NCI is diagnosed to avoid a potentially 

irreversible neurological damage. Additional treatment strategies are needed in patients 

with persistent NCI despite HAART. 

ABSTRACTS 


OP 3.4 

Fertility options in HIV-infected patients 

Aide médicale à la procréation dans l'infection à VIH 

Jeanine OHL, Strasbourg, France, jeanine.ohl@sihcus.fr 

Among new seropositivities in France in 2003 and 2004, 42% are women. Infected women 

are younger than men. Highly active antiretroviral therapies allow an efficient long term 

control of the disease, allowing an important diminution of new cases of AIDS and of 

mortality and allowing a dramatic drop of mother to child transmission. The rate is now 

less than 1%. The wish to have a child can be expressed and taken into consideration. 

And so, we assist to an increase of pregnancies for seropositive women in France. 

How to become a parent avoiding contamination of the partner and mother to child 

transmission? For seropositive men unprotected intercourse remains not advised. 

Insemination with donor sperm is no longer proposed because of assisted reproductive 

techniques. For seropositive women self inseminations are suggested first and assisted 

reproductive techniques come secondary in case of infertility. They are interesting 

because they avoid contamination of the partner and they allow to treat a possible 

infertility. 

The first programs concerned only seropositive men, first in Italy and in Spain, then in 

France. IUI or IVF were performed with semen validated for HIV and no contamination 

was observed. The French law has changed in May 2001: medical care is possible for 

seropositive men and women in ART centres, but a specific lab must be created, s 

eparated in time or in space. Pluridisciplinary care must be possible and well-organized. 

A specific written consent is signed by both members of the couple and they testify of 

protected sex. For men and perhaps more for women, psychologic support and advice are 

proposed. 

The clinicians ensure that the infection is well-controlled with a CD4 count higher than 200 

and a stable plasmatic viral load, twice in the four months before inclusion. The other 

serologies are checked too. For infected men, semen is prepared with 2 successive 

techniques every time it is possible (gradient centrifugation and spontaneous migration). 

The ART technique is chosen according to medical history and also according to viral 

findings in semen. When viral load is low in seminal plasma, every technique can be 

proposed, when viral load is between 1000 and 10 000, ICSI must be used. Of course the 

final fraction must always be detected as negative for the semen to be used. When viral 

load is higher than 10 000 in seminal plasma, the final fraction cannot be used. 

When the female partner is not infected, she must be controlled as seronegative and with 

a negative plasmatic viral load two weeks before the ART attempt. After the procedure she 

is controlled in the same way after 3 weeks, after 3 and 6 months and at delivery. 

For infected women, the treatment against HIV must be reconsidered in regard to a 

possible pregnancy with as low a toxicity as possible and with as low a plasmatic viral load 

as possible at the end of pregnancy. 


As the man is seronegative, his semen is prepared in the usual lab. When IVF is 

performed, the follicular fluid is treated in the viral risk lab. When IUI is performed, no 

specific lab is required but seropositive women are referred to the specific centres to allow 

a correct registration. 

Some French results concerning ART for seropositive couples were given in December 

2005 by the Agence de Biomédecine. The enquiry was led in 2003 and 2004 and 

concerned 11 centres. The number of attempts is stable for seropositive men between 

2003 and 2004. For women the number is increasing. 

The number of inseminations has increased between 2003 and 2004. Respectively 13 

and 17% of the inseminations lead to an onging pregnancy (men or/and woman 

seropositive). The number of IVF or ICSI has slightly increased between 2003 and 2004. 

Respectively 18 and 20% of the procedures lead to an onging pregnancy, frozen embryos 

included (men or/and woman seropositive). 

When considering together seropositive men and women, more than 75% of the babies 

were born after insemination in 2004. This can be explained because the seropositive 

partner is the male in 2/3 of the cases. Their semen is often normal and their female 

partner have no infertility. Results can be different when you consider only seropositive 

women whose self-inseminations failed. 

ABSTRACTS 

In our centre in Strasbourg, 87 seropositive men gave semen for ART from January 2001 

to December 2005. Seminal plasma was positive with more than 10 000 copies in 4 cases 

and uninterpretable in 5 cases (inhibitors). These samples could not be used. Seminal 

plasma was positive less than 10 000 copies in 18 cases and negative in 116 cases 

allowing the negative final fraction to be used for ART. Final fraction was positive in tree 

cases for RNA and in one case for DNA, so these samples were discarded. These findings 

confirm that the viral validation of processed semen is necessary in ART programs. Final 

fraction was uninterpretable in 6 cases and another semen sample had to be tested for 

these patients. 85,3% of the samples could be used immediately. 

In our Centre 122 couples underwent an ART procedure. IUI is not performed as often as 

IVF because more than half of the couples include infertile seropositive women. For them 

IVF is the procedure of choice. But even with IVF or ICSI results for women are much 

lower than for men (19% of the couples became parents in case of female seropositivity 

vs 50% for male seropositivity). Three main explanations can be taken into account: 

- women are more often really infertile (otherwise self-inseminations would have worked), 

- we perform mainly elective single embryo transfers to avoid multiple pregnancies and 

- ovarian response to stimulation may be impaired as a result of the infection. 

Nevertheless these results are acceptable. 

Pluridisciplinary teams are proud of their ART programs because, in spite of many 

difficulties, the wish to become parents can become true for many seropositive couples. 

ART must be considered as a tool of a victory against discrimination as well as against the 

spreading of the epidemic. 


OP 3.5 

Non-AIDS defining cancers in the era of HAART 

Dr. Nancy Crum-Cianflone, San Diego - USA 

Early in the HIV epidemic it was suggested that a second "epidemic" due to malignancies 

may occur; this has been realized, and three cancers (Kaposi's sarcoma, non-Hodgkin's 

lymphoma, and invasive cervical cancer) have been classified as AIDS-defining cancers 

(ADCs). Since the advent of highly active antiretroviral therapy (HAART), the number of 

opportunistic infections and ADCs (especially Kaposi's sarcoma) has dramatically 

declined. However, the number of non-AIDS-defining cancers (NADCs) has 

proportionally increased, and cancer remains a leading cause of morbidity and mortality 

among HIV-infected persons. The reasons for the increase in NADCs includes 

co-infection with oncogenic viruses, increased life expectancy, reduction of competitive 

causes of death, and behaviors including tobacco use among this population Unlike 

ADCs, NADCs do not correlate with the degree of immunosuppression. This lecture 

describes trends in cancer incidence rates during the AIDS epidemic, reviews the most 

common cancers in the era of HAART, and explores the pathogenesis of NADCs among 

HIV-infected persons. 

OP 4.1 

New Antiretrovirals in the Pipeline: 

from Already Known Targets to Integrase Inhibitors 



OP 4.2 

Development of Aprictabine 

Dr Susan Cox, Avexa, Richmond, Australia 

Background 

Apricitabine (ATC) is a deoxycytidine analogue in phase IIb development for the treatment 

of HIV infection. Prior to 2006 ATC was named variously as BCH10618, SPD754 and 

AVX754. In vitro and in vivo studies undertaken previously identified a promising 

tolerability profile, with antiretroviral activity against clinical isolates resistant to both 3TC 

and TAMs and a more than 1.6 log10 reduction in viral load over 10 days monotherapy in 

treatment naïve subjects. ATC is neither a substrate nor an inducer of CYP450 

isoenzymes and is principally eliminated as unchanged drug in the urine. ATC is dosed 

twice daily at present and is a candidate for the management of patients who are resistant 

to 3TC or FTC. An ongoing study is currently investigating the potential for ATC to 

provide superior antiretroviral activity to 3TC in the presence of the M184V mutation in 

reverse transcriptase. Studies have shown that co-administration of more than one 

deoxycytidine analogue may result in clinically significant antagonism. Avexa is presently 

completing a series of further in vitro and in vivo studies prior to initiation of a phase III 

clinical program. 

ABSTRACTS 

Methods 

Two in vitro studies have been completed to expand the understanding of the virological 

profile of ATC. In the first of these, HIV-1 (HXB2) harbouring M184V was repeatedly 

passaged with increasing concentrations of ATC in order to identify if ATC (which can 

maintain M184V in vitro) would select for further mutation in reverse transcriptase. In the 

second experiment the IC50s for ATC and approved NRTI were investigated against a 

panel of clinical isolates containing K65R in the presence or absence of M184V. Three 

further clinical pharmacology studies have either been completed or are ongoing. In the 

first of these studies 16 healthy volunteers were administered ATC 800 mg twice daily 

alone and with up to 960 mg per day of Septrin (Trimethoprim/Sulphamethoxazole). 

A second study is investigating the pharmacokinetics of ATC in the presence of steady 

state concentrations of a protease inhibitor, tipranavir. Finally a thorough QTC study is 

underway in accordance with regulatory guidance. 

Results 

Passaging M184V virus in the presence of ATC for up to 8 weeks did not result in the 

selection of further mutations in reverse transcriptase. The IC50s for other NRTI against 

K65R and M184V+K65R were within the range of fold changes from wild type previously 

reported elsewhere. For ATC the fold changes for K65R viruses ranged from 2.1 to 3.2 

and for K65R+M184V from 2.5 to 4.2, in agreement with previous data in the HXB2 

background. Co-administration of ATC with Septrin resulted in an increase in ATC 

AUC0-12 of 55% and in Cmax of 22%, similar to that seen previously for 3TC. 

Conclusions 

Apricitabine displays only limited fold changes in activity against HIV-1 viruses harbouring 

important resistance mutations in reverse transcriptase. Other than the known class 

interaction with other deoxycytidine nucleoside analogues, ATC shows little potential for 

meaningful interactions with other ART. 


OP 4.3 

Update on TMC114 - Actualités sur TMC114 

Diego Miralles, Mechelen - Belgium 

Darunavir is an inhibitor of the HIV protease selected for clinical development based on 

its potency, high barrier to resistance, and activity against most protease inhibitor-resistant 

HIV found in drug-experienced HIV-infected individuals. Two studies (POWER 1 and 2) 

conducted in treatment experienced patients with evidence of PI resistance demonstrated 

that TMC114 provided significant improvements in virological and immunological 

endpoints compared to control PIs. Based on these results, TMC114 has been submitted 

for regulatory approval worldwide. The clinical development program of TMC114 

continues with additional studies in treatment experienced and treatment naïve patients. 

The presentation will describe the clinical development program for TMC114. 


OP 4.4 

The Discovery and Exploratory Development of Maraviroc (UK-427,857): 

A Novel CCR5 Antagonist for the Treatment of HIV 

C. A. Hitchcock, Pfizer Global Research and Development, Sandwich Laboratories, 

Sandwich CT13 9NJ, UK 

Maraviroc is a novel CCR5 antagonist and is the most advanced clinical candidate in 

Pfizer's CCR5 discovery and development programme. It is exquisitely selective for the 

CCR5 receptor and demonstrates potent activity in vitro against both lab-adapted and 

primary clinical HIV isolates spanning all of the clades, including viruses that are resistant 

to current classes of HIV agents. Maraviroc has been evaluated in >500 volunteers and in 

95 HIV patients where it is well tolerated at doses in excess of those required to block the 

CCR5 receptor and those providing free drug levels above the in vitro concentrations for 

potent antiviral activity. Consistent with this, Maraviroc has demonstrated encouraging 

short-term (10 day), single agent efficacy as measured by reductions in viral loads in 

asymptomatic HIV patients; doses of 300mg QD and 300mg BID resulted in mean 

maximum HIV RNA reductions of 1.60log10 and 1.84log10, respectively. The clinical 

pharmacology of Maraviroc has been studies extensively in volunteers. It is a substrate for 

cytochrome P-450 3A4 (CYP 3A4), but it does not significantly inhibit or induce CYP 3A4 

or other cytochrome P-450 enzymes. Studies both with CYP 3A4 inhibitors and inducers 

have demonstrated that Maraviroc will have manageable drug interactions when used in 

the setting of HIV patients receiving HAART. In summary, Maraviroc has potency, 

pharmacokinetic and toleration profiles that merit its further evaluation as a new therapy 

for patients with HIV/AIDS, and Phase III studies are underway. 

ABSTRACTS 


OP 4.5 

Recent data on PA-457 Maturation Inhivitor 

David. E. Martin, PharmD 

Panacos Pharmaceuticals Inc., Gaithersburg, MD. 

Background: PA-457 is the first in a new class of antiretrovirals that inhibit HIV replication 

by disrupting virus maturation. PA-457 blocks a late step in Gag processing, resulting in 

defective core condensation and the release of non-infectious virus particles. Specifically, 

PA-457 disrupts the conversion of the capsid precursor, p25 (CA-SP1), to mature CA 

protein, p24. PA-457's mechanism of action (MOA) is distinct from that of protease 

inhibitors in that it appears to directly target the Gag precursor protein rather than the 

protease enzyme that is responsible for Gag processing. This report describes the in vitro 

antiviral profile of PA-457 and results from clinical studies in normal, uninfected volunteers 

and HIV-1 infected patients. 

Methods: We analyzed the activity of PA-457 against a panel of HIV-1 isolates resistant to 

NRTIs, NNRTIs or PIs. MOA studies focused on events late in the virus life cycle including 

protease function and viral protein processing. PA-457-resistant isolates were generated 

by serial passage of virus in the presence of increasing concentrations of compound. 

Phase 1 and Phase 2 clinical studies have been conducted to evaluate the safety, 

pharmacokinetics and antiretroviral potency of PA-457 and its potential for drug-drug 

interactions. 

Results: PA-457 retains low nM IC50 against all drug-resistant HIV-1 isolates tested. MOA 

studies indicate that PA-457 inhibits virus replication by causing a defect in Gag 

processing, specifically the conversion of p25 to p24. As a result of this block, virions 

produced in the presence of PA-457 are defective for capsid condensation, exhibiting 

spherical electron-dense cores and a second crescent-shaped electron-dense structure 

lying just beneath the viral membrane. Furthermore, genotypic analysis of 

PA-457-resistant virus indicates that mutations that confer resistance map to residues 

flanking the p25 to p24 processing site. Clinically, multiple oral doses up to 200 mg of 

PA-457 administered once daily for 14 days were safe and well tolerated. In a 10-day 

monotherapy study, PA-457 produced statistically significant reductions from baseline in 

HIV RNA of up to 1.78 log10 in the 200 mg QD dose group. These data suggested that 

the plateau of the dose response relationship had not been reached. Population 

sequencing of the CA-SP1 cleavage site from patients in the highest dose group (i.e., 

200 mg QD) found no mutations known to cause a reduced sensitivity to PA-457. 

Drug-drug interaction studies were conducted with PA-457 and atazanavir and ritonavir, 

which suggest that PA-457 has a limited potential for clinically relevant interactions. 

Conclusions: PA-457 is the first in a new class of drugs called Maturation Inhibitors. 

It utilizes a novel mechanism of action to potently inhibit HIV-1 replication of all 

drug-resistant HIV-1 isolates tested. Clinical studies suggest that PA-457 has a low 

potential for clinically relevant drug-drug interactions. Monotherapy studies with PA-457 

have demonstrated potent antiviral responses. Future clinical studies will explore higher 

doses to attain the maximum antiviral effect and evaluate the durability of the antiviral 

response. 


OP 5.1 

Genetic Analysis of the Env Gene of Human Immunodeficiency Virus Type 1(HIV-1) 

Strains from Patients in Cyprus from 1994 Until 2005: Evidence of a Highly Evolving 

Epidemic 

Ioanna Kousiappa, Alina Giantsiou-Kyriacou, Efthymia Yiacoumi, Victoria Demetriou and 

Leondios G. Kostrikis 

Department of Biological Sciences, University of Cyprus, 75 Kallipoleos Avenue, P.O.Box 

20537, CY-1678, Nicosia, Cyprus 

ABSTRACTS 

Background 

The aim of this research was the investigation of the genetic variation of newly arrived 

HIV-1 strains that were isolated from Cypriot patients in 2005 and the comparison of the 

results with those obtained from a corresponding study carried out in 1994. 

Material and Methods 

Peripheral blood mononuclear cell (PBMC) samples were extracted from the blood of 141 

HIV-1 patients with their informed consent. DNA was extracted and the C2-C5 region of 

the Env gene was amplified by means of nested PCR and sequenced using the ABI 3130 

Genetic Analyzer. Sequence alignment was done through ClustalX and genetic subtypes 

were identified by phylogenetic analysis using neighboring-joining with Kimura's 

two-parameter method. 

Results 

The phylogenetic analysis of 137 samples reveals that 69% of patients have the subtype 

B, 19% ?, 8% C, 1,5% F, 1% D and 1% CRF04_cpx. 1.5% of the samples were not 

recognized. In an analogous investigation in 1994, 24 strains from Cypriot patients were 

studied and the results were 63% ?, 17% ?CY, 4% C, 8% FCY and 8% CRF04-cpx 

exhibiting multiple introductions of subtype B and unique introductions of subtypes ?, 

C, F and the CRF04_cpx. 

Conclusion 

These newly found data demonstrate a heterogeneous epidemiological status of HIV-1 in 

Cyprus. Subtype B is the most dominant with a wider range of strain variation compared 

with the other subtypes, showing multiple introductions from other geographical regions. 

Compared to the 1994 study, the number and the variation of the strains of subtypes A and 

C have increased due to introductions of new ones. The ?CY, FCY subgroups and the 

CRF04_cpx that were detected in 1994 did not spread further. In the present study, a new 

introduction of subtype F has appeared and a strain of subtype D has been found for the 

first time. 

OP 5.2 

Therapy and New ARV Interactions 



OP 5.3 

Immunology - Summary of advances in HIV during the last year 

Guido Poli, San Raffaele Scientific Institute, Milano, Italy. 

The immunology of HIV infection is typically characterized by "waves" of fashionable 

models tending to the holistic explanation of the reasons for failing viral clearance and, 

conversely, indicating which directions should be taken for solving this modern plague. 

In terms of the immune response, most of the emphasis in recent years has been 

attributed to the cellular (CD4 and CD8) rather than humoral (antibody, Ab) immune 

response to the virus; several experimental vaccine trials have been designed and are 

under current evaluation in light of the hypothesis that, indeed, a robust, multi-targeting 

cellular immune response to the virus would provide the key, if not to viral eradication, to 

prolonged, therapy-free control of viral replication and pathogenesis. Unfortunately, most 

of the studies, while providing interesting insights in terms of the defects characterizing 

both CD4+ T helper cells and cytolytic T cells (CTL) in HIV infection (such as the 

unbalanced expression of interferon-γ and interleukin-2, this latter being substantially 

defective, in CTL of HIV+ individuals) have not indicated thus far a clear direction to 

undertake. Conversely, a "renaissance" period of great interest in the capacity of Ab to 

prevent and control early infection has been substantiated by both animal studies and by 

experimental clinical trials in humans showing (partial) protective effects against SIV/HIV 

infection by combinations of anti-Env monoclonal Abs. In this regard, the potential role of 

autoreactive Ab displaying neutralizing activities against the virus has been recently 

debated. In terms of pathogenesis, infection of the gut-associated (mucosal) lymphoid 

tissue (GALT) has replaced the previous emphasis on other secondary lymphoid tissue 

such as lymph nodes, although the implication of these studies may have been 

overemphasized. The modalities of resistance and susceptibility to infection via genital 

mucosa, a dominant modality of HIV transmission in both the developed and 

underdeveloped countries, including the hypothesis that resting CD4+ T cells are the 

primary sites of an initial productive infection, remain to be validated and fully understood 

in the perspective of developing safe and effective microbicides as part of a preventive 

strategy against the infection. 


OP 6.1 

Social Representations of HIV/AIDS in Central and Eastern Europe 

Robin Goodwin, London 

Objectives: HIV/AIDS is increasing at an alarming rate in the countries of the Former 

Soviet Union (FSU), with the majority of this increase amongst adolescents and young 

people. This project had four objectives. 1) To explore lay representations of HIV/AIDS 

amongst 13-17 years old school children and similar aged children attending homeless 

shelters in three countries of the FSU (Russia, Georgia, Ukraine). 2) To investigate 

high-risk behaviours amongst this population in these countries (unsafe sexual 

behaviours, illicit drug use). 3) To explore the relationship between individual values, lay 

representations of the epidemic and these high-risk behaviours. 4). To examine wide 

societal perceptions of the epidemic through an analysis of the media read/ viewed by 

these adolescents, and through intensive focus groups held with representative groups of 

adolescents. 

ABSTRACTS 

Methods. A structured interview and questionnaire knowledge, representations of 

HIV/AIDS sexual behaviour and hedonistic values amongst 1531 14-17 year old school 

children and similar aged shelter children in Russia, Georgia and Ukraine (N > 500 per 

country). Detailed media analysis of the most read newspapers and watched TV and radio 

programmes in each country. 32 single-sex focus groups held at 3 times periods 

(3 monthly intervals) in the three countries, plus control groups to assess impact of focus 

groups on lay representations of the epidemic and reported sexual behaviour and drug 

use. 

Results Shelter children are more sexually active, less knowledgeable means of HIV 

transmission, and more likely to hold stereotyped representations of those most at risk, 

but findings are partly moderated by culture and individual values, with Georgian 

school-children more likely to have had early sexual experience than street children 

(logistic regression (culture x group) Wald = 54.03, p< .001). Georgians are the least 

knowledgeable about HIV, and most likely to hold misleading representations, although 

Russians the most likely to have multiple partnerships and to take illicit drugs (F = 5.28, 

p< .001). Hedonistic and fatalistic values a significant predictor of multiple sexual 

partnerships and illicit drug use and mediate cultural differences in these behaviours. 

Russian media focused primarily on overseas personalities, whilst Georgian coverage of 

HIV/AIDS the least detailed. Ukrainian coverage the most in-depth and concerned with the 

problem in that country. Participants in focus groups demonstrated significantly greater 

knowledge of epidemic (F (1, 164) = 7.26, p< .01), and to have reduced some 

misrepresentations of epidemic, in comparison with control group. Shelter children in the 

focus groups reduced partnerships over six months compared to the control group, but no 

clear effect for school children. 

Conclusions. This is the first, large-scale study of HIV/AIDS amongst young people in this 

region. The results indicate the significance of individual psychological, group and cultural 

effects on sexual behaviour and drug use, and suggest the potentially important role of the 

media in helping perpetuate or challenge persisting societal myths about the epidemic. 


OP 6.2 

Molecular Epidemiology of HIV-1 infection: tracing how the epidemic spreads 

Dimitrios Paraskevis 

National Retrovirus Reference Center, Department of Hygiene and Epidemiology, Faculty 

of Medicine, National and Kapodistrian University of Athens 

HIV-1 originated in Africa through cross-species transmission from the chimpanzees 

infected with simian immunodeficiency virus (SIVcpz). The majority of HIV-1 infections 

worldwide have been caused by group M that became pandemic in contrast to group O 

localized in west-central Africa, and group N, which has been documented only among a 

few individuals in Cameroon. The group M has been classified into subtypes, 

sub-subtypes and circulating recombinant forms (CRFs). 

The prevalence of the different subtypes and CRFs differ according to the geographic 

origin. The global distribution of the different HIV-1 clades provides information about the 

origin and the way of spread of the infection. The spillover of the infection occurred from 

the Democratic Republic of Congo (DRC) to the neighbouring countries in Africa (e.g. 

Congo-Brazaville, Uganda, Tanzania and Zambia) by establishing monophyletic 

epidemics of non-B subtypes in these areas. Similarly, the epidemic was spread in 

Western countries, as a founder effect of subtype B, originated from Africa. 

Introduction of the HIV-1 epidemic in Europe mainly occurred through sexual exposure to 

men in the USA, or through heterosexual contacts with individuals from Central Africa. 

During the early stages of the AIDS epidemic (early eighties), the prevalence of the 

HIV-1 infection was higher among men having sex with other men (MSM) compared to 

heterosexuals. For this reason subtype B, which was exclusively identified among MSM 

in the US, was the predominant clade in Europe before nineties. The prevalence of 

non-B subtypes have been increasingly recognized the last years in Europe and other 

than B clades are mainly associated with immigrants or heterosexuals epidemiologically 

linked with sub-Saharan Africa. In contrast to other European countries, subtype A 

predominates in several areas in Russia, especially after 1997 when the epidemic start 

spreading at a very high rate among IDUs. 


OP 6.3 

HIV/AIDS epidemic in Ukraine 

Pavlo Kyrychenko, MD, PhD 

Department of Infectious Diseases and Epidemiology, Vinnitsa National Pirogov Medical 

University, Ukraine 

During the past years, most countries of the former Soviet Union have been severely 

affected by HIV epidemics. The available data suggest that the Russian Federation, 

Latvia, Ukraine, and Estonia are now experiencing some of the fastest growing HIV 

expansion in the world. Since Russia and Ukraine account for some two thirds of the 

population of the former Soviet Union (FSU) countries, and since citizens in these 

countries travel freely (on a visa-free basis) to other FSU countries, epidemiological trends 

in Russia and Ukraine clearly have a major influence on trends in other FSU countries. 

ABSTRACTS 

To further understand the development and recent trends of the HIV epidemic in Ukraine, 

we analysed HIV/AIDS surveillance data and reviewed published studies and reports. The 

first stage search procedure gathered information from reports and fact sheets of local and 

international organizations including Ukrainian Centre for AIDS Prevention/ Ministry of 

Health of Ukraine (UCAP), Joint United Nations Program on HIV/AIDS (UNAIDS), World 

Health Organization (WHO), United Nations Office on Drugs and Crime (UNODC), United 

Nations Development Program (UNDP), and International HIV/AIDS Alliance. Further, we 

searched the literature up to January, 2006, using the appropriate MeSH terms and the 

explode function in PubMed, and identified relevant publications in English. Russian and 

Ukrainian language literature were searched via local Medical Library catalogues. In our 

review we did not consider media publications, newspaper articles and conference 

abstracts. Over 100 papers and reports were reviewed. 

Given the relatively uniformity of case reporting procedures in the country, an analysis of 

the number of HIV infections detected through case finding and screening, and the 

proportions of HIV-positive cases among groups routinely tested was expected to provide 

a reasonable insight into patterns and trends of the epidemic. These data suggest that 

prior to 1994 Ukraine was not experiencing an epidemic of HIV; there were sporadic 

occurrences, mainly among non-Ukrainians. During this initial period (from 1987 to 1994) 

only 183 HIV cases were officially registered among Ukrainian residents (fig. 1), however, 

even at this low level of transmission the infection had reached all administrative regions 

of the country. The majority of the few, adult reported cases of HIV were acquired through 

heterosexual and homosexual contacts. 

Figure 1. Trends in newly diagnosed HIV infections, AIDS cases and 

AIDS deaths (1987-2005) in Ukraine (annual rates per 100,000 

population) 

AIDS cases and deaths per 

100,000 population 

10,0 

35,0 

9,0 

AIDS cases 

30,0 

8,0 

AIDS deaths 

7,0 

HIV cases 

25,0 

6,0 

20,0 

5,0 

4,0 

15,0 

3,0 

10,0 

2,0 

5,0 

1,0 

0,0 

0,0 

1987- 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 

1995 

Year of report 

HIV cases per 100,000 

population 


In 1995 HIV started to spread rapidly within the population of injection drug users (IDUs). 

About 81% of the 5400 new officially registered cases in 1996 were among drug users (fig. 

2), while the highest number of HIV positive drug users was registered in 1997 - 7448 

persons (84% of the total registered cases). A dramatic decline in drug use related HIV 

incidence, as well as in total annual incidence, occurred in 1999 (respectively 42% and 

32% year decrease). This was mostly the consequence of implementation in April 1998 

the Government Decree 'About prevention of Acquired Immunodeficiency Syndrome and 

social advocacy of the population', which for the first time declared the principle of 

voluntary HIV testing in the country. To date, the annual number of newly reported HIV 

cases continues to rise and exceeded 13,700 in 2005, almost 10% more than the 12,500 

cases diagnosed in 2004 and almost double the number diagnosed in 2000 (fig. 1). 

The epidemic is rapidly spreading beyond the ten regions in southern and eastern Ukraine 

where over two thirds of all HIV cases have been reported to date. Sharp increases in new 

reported infections are also occurring in central regions of Ukraine previously thought to 

be minimally affected. 

Figure 2.HIV transm ission trends in Ukraine 

(% of som e transm ission groups am ong new ly diagnosed HIV 

infections by year) 

% of tran sm ission groups 

90 

Heterosexual 

80,7 83,6 

80 

Injection drug use 

76,0 

Mother-to-child 

70 

61,2 

64,7 

62,5 

60 

56,6 

52,4 

50 

48,1 46,3 

40 

30,4 

32,4 

28,5 

30 25,9 

26,9 

22,7 23,0 

16,2 

18,3 18,2 

20 

15,7 

13,1 11,3 

13,1 

11,7 

9,0 

10 

4,4 

1,1 1,7 2,2 

0 

1987- 1996 1997 1998 1999 2000 2001 2002 2003 2004 

1995 

Year of report 

To date, among other vulnerable groups the highest HIV prevalence continues to be 

among injecting drug users, ranging today from 10% to 66% among 13 HIV sentinel 

surveillance sites in 2005, with the most affected southern and eastern cities (Donetsk, 

Odesa, Mykolaiv, and Simferopol) as well as the capital of the country (Kyiv) and a city of 

the central region - Zytomyr. Because HIV testing is limited to government facilities, those 

at greatest risk are not being reached, since marginalized populations are the least likely 

to use government facilities. This could result in significant under-identification of new HIV 

cases. In fact, number of HIV tests among injecting drug users nationwide decreased by 

153.2% between 1996 and 2004, despite this, however, HIV prevalence among drug 

users is steadily increasing showing the rate of 14.8% by the end of 2004. A recent 

survey embraced 14 regions and about 3,450 injection drug users reported that in 

average 21% of the participants might be HIV positive. 

Prevalence rates decreased or remained stable in recent years in several cities. However, 

these trends probably reflect increasing participation bias over time due to progressive 

exclusion of known HIV-positive individuals from the tested population, rather than true 

decreases in prevalence. Also, these trends might be a consequence of high AIDS death 

rates among infectious drug users in these regions. For example, in Donetsk where HIV 

prevalence among IDUs remains relatively stable from 2002 to 2004 (around 40%), AIDS 

death rates increased by 123% during the same period. 


Certain aspects of drug use in Ukraine make users more vulnerable to HIV infection. The 

most commonly injected opiates in Ukraine are kitchen-based domestically produced 

derivatives of poppy straw and between 70% and 95% of Ukrainian IDUs inject these 

drugs regularly. Injection "amphetamine-like" drugs are also domestically produced from 

readily available chemicals that can be purchased at drug stores and local pharmacies. 

Methods of liquid drug production may have a direct link with HIV transmission. HIV may 

enter the production process via containers and mixes used to collect up, decant and mix 

the solutions ingredients during and between heating, and via injection equipment used to 

test the liquid directly from mixing containers. Moreover, human blood may be added to 

the drug solution in order to stabilize acidity or as a cleansing agent. This practice was 

reported by 10% to16% of the IDUs nationwide, among them almost one third did not heat 

the solution after adding blood. About 34-43% received narcotic substances by filling a 

syringe from a common container; 26-35% filled their syringes from the dealer's syringe; 

one fifth received drugs in a readily filled syringe. About 27-43% of IDUs reported sharing 

mixing containers in the month prior to interview in 2001-2004. 

ABSTRACTS 

Available data suggest that reported levels and frequency of needle or syringe sharing 

among IDUs in Ukraine are relatively high. In a synthesis of studies conducted between 

1999 and 2003, reported rates of ever sharing needles and syringes varied between 14 

and 40% in the majority of cities. A recent nationwide study suggests that at least 29% of 

IDUs practiced receptive needle or syringe sharing in the month prior to interview. About 

50-70% of the IDUs use their own syringes repeatedly, while majority among them take a 

drug dose from the shared containers and "disinfect" syringes by water and moreover in 

the shared utensils. Although there is some emerging evidence for changes in injection 

behaviour among IDUs attending needle exchange, coverage rates of IDU populations by 

harm reduction programmes are currently low, and were recently estimated at only 

10-15%. 

While the use of injected drugs continues to predominate, since 1997 the proportion of 

IDUs among all officially registered HIV-positive Ukrainians has dropped, from a peak of 

84% to 46% in 2004. At the same time, the proportion of new HIV diagnoses attributed to 

heterosexual transmission has increased continuously between 1996 and 2004, from 13% 

to 32% (fig. 2). With women accounting for 42% of people newly-diagnosed with HIV in 

Ukraine in 2004, the number of children born to HIV-positive mothers continued to rise, 

and was over 2,200 in that year (66% increase as compared to 2002). 

About 63-87% of IDUs reported sexual contacts during three months prior to the interview 

and about 39-43% of sexually active IDUs were engaged in sex with multiple partners. 

Based on surveys among IDUs, 44-60% of them have casual sexual partners and 20-60% 

have partners who are not IDUs. Regular condom use rates were only 15-28% among 

those who were sexually active and about 37-45% seldom or never used condoms. 

Available data also suggest that about 40% of those who had sexual contacts with casual 

partners used condoms consistently, while only 15-25% declared using condoms with 

regular partners. Among those who declared their HIV positive status about 45% had more 

than three casual sexual contacts during the month prior to interview, while only 60% 

reported regular condom use. 


Given the high HIV prevalence in IDU populations, with high rates of sex with non-IDU 

partners and sub-optimal condom use rates, the risk of "firs-wave" transmission through 

non-commercial sex might be high. Commercial sex acts are also likely to be important in 

terms of generating significant heterosexual transmission in non-IDU populations, since 

here there is the potential for multiply unprotected sexual contacts with large numbers of 

different non-IDU clients. 

Evidence suggests that the number of female sex workers (FSW) in countries of Eastern 

Europe has increased exponentially following the collapse of the Soviet Union. There also 

appears to be a high degree of overlap between injection drug use and commercial sex. 

Estimates of the proportion of female sex workers who inject drugs vary between 25% and 

80%. In Mykolaiv 32% of sex workers were HIV positive, while in Donetsk, Lutsk, Poltava, 

and Odesa the corresponding figure ranged from 25% to 29% in 2005. Data from the 

recent nationwide study showed that 58% of the female sex workers in Ukraine had from 

5 to 25 clients per week, consistent use of condoms was relatively low (54% during the 

month prior to the interview), 45% of the FSW had IDUs and 25% had bisexual or 

homosexual men among their clients. Thus, FSW might be considered to be an HIV 

bridge between IDUs and general population in Ukraine. Moreover, this group might serve 

as a bridging population between IDUs and another vulnerable population of special 

importance - men who have sex with men. 

A limited number of recent studies among men who have sex with men indicate high levels 

of risk taking and a high frequency of bisexuality, which has implications for HIV diffusion 

into the heterosexual population. In a study in gay venues in 7 cities (886 men), 40% 

reported unprotected anal sex, 54% of sexually active persons did not have a permanent 

sexual partner, around a third had had both male and female sex partners in the past 6 

months, and around 22% had recently exchanged sex for money. About 14% reported a 

sexually transmitted infection in the past 6 months. At the same time, injecting drug use 

was not appeared to be widespread in this group. Only 6% of the respondents declared 

ever injecting drug using. 

Although Ukraine decriminalised consensual sex between adult men in 1991, men who 

have sex with men are still largely inaccessible to sentinel research due to stigmatization. 

Yet, there are signs that prevalence in this population group could be very high. In the 

sentinel surveillance conducted in 2005 among men who have sex with men, five of 

26 men in Odessa were found to be HIV-positive, as were two of the 23 men tested in 

Mykolaiv. Knowledge and awareness of AIDS among this population is also poor, and risky 

behaviour appears widespread. In a study in seven Ukrainian cities, only 55% of men said 

they had used a condom the last time they had sex with a man. 

Numbers of newly reported AIDS cases in Ukraine began to rise dramatically in the 

mid-1990s, from 45 in 1995 to 4,222 in 2005 (120% increase compared to 2003). Likewise 

for AIDS deaths: from 20 in 1995 to 2,185 in 2005 (70% increase compared to 2003). 

At the same time, not all those who died of tuberculosis and other diseases secondary to 

AIDS were tested for HIV in their lifetimes, so these numbers do not show the whole 

picture. 


Mentioned above figures illustrate only officially registered cases of HIV/AIDS: the actual 

number is estimated to be much higher. National legislation to this day specifies that 

people be only registered as HIV-positive if they have undergone both clinical and 

laboratory testing and if their data are "personified". Consequently, the cumulative number 

of officially registered HIV cases in Ukraine, about 88,626 at December, 2005, may 

represent only 20% of the real number of infected people. UNAIDS estimated that the 

number of people infected with HIV in 2003 was 360,000 (range 180,000 to 590,000), 

representing an adult prevalence of 1.4%, the highest prevalence rate in Europe and 

among former Soviet Union countries. Still, official statistics record a cumulative total of 

only 7,552 deaths due to AIDS between 1987 and 2005, there is reason to believe this 

figure is almost certainly undercounted. Number of AIDS deaths at the end of 2003 was 

estimated by UNAIDS as 20,000 (range 9,600 to 33,000). 

ABSTRACTS 

Clearly, Ukraine faces large-scale and growing HIV epidemic. Some preventive projects in 

the country appeared to improve HIV related knowledge, tolerance to people living with 

HIV and encourage safer behaviours among vulnerable populations. However, few in 

number and limited in scope, they are dwarfed by a large epidemic. In the absence of a 

scaled-up national response to the combined challenges of HIV, drug injecting and sexual 

risk behaviour, Ukraine's HIV epidemic can be expected to continue expanding. 


OP 6.4 

The Epidemiology of HIV & STIs in Slovenia 

Irena Klavs, MD, MSc, PhD 

Institute of Public Health of the Republic of Slovenia, Ljubljana, Slovenia 

Introduction 

Human immunodeficiency virus (HIV) and sexually transmitted infections (STI) surveillance 

and research is essential for the development of evidence based prevention and control. 

Methods 

HIV and STI surveillance in Slovenia is based on (1) universal cases reporting; (2) 

monitoring changes in HIV infection prevalence (among men who have sex with men 

(MSM), injecting drug users (IDU), patients of clinics for sexually transmitted infections 

(STI), and pregnant women); and (3) behavioural surveillance among MSM and IDU). This 

information is complemented by special studies on STI and sexual behaviour. 

Results 

During the last 5 years, annual reported incidence rates varied for HIV infection from 6.5 

to 17.5 per million population (17.5 in 2005), for newly diagnosed early syphilis from 0.2 

to 1.5 per 100000 (1.5 in 2005), for gonorrhoea from 2.3 to 2.9 per 100000 (2.3 in 2005), 

and for chlamydia from 7.6 to 11.5 per 100000 population (11.5 in 2005). From 2000 to 

2004 the national annual HIV prevalence estimates for IDU varied from 0% to 0.8% and 

for MSM from 0% to 3.5%. In 2003, HIV prevalence among STD patients was 0.2% and 

among pregnant women 0%. The proportion of IDU reporting sharing needles and 

syringes at first treatment demand has decreased from 42% in 2000 to 27% in 2003. The 

proportion of MSM who reported to have never used a condom at anal sex during the 

preceding year doubled in 2002 and 2003 in comparison to 2000. In the first national 

general population probability sample survey, chlamydial infection was diagnosed in 3.0% 

of men and 1.6% of women. Prevalence was highest in men and women aged 18-24 years 

(4.1% for both). 

Conclusions 

Slovenia remains a country with a low level HIV epidemic. The most affected group are 

MSM. Reported STI rates underestimate the burden of infection. A relatively high 

prevalence of genital chlamydial infection among 18-24 year old Slovenians, in contrast 

with relatively low-risk sexual behaviour and low reported incidence rates of chlamydia 

infection, suggest that there may be serious gaps in diagnosing and treating the condition. 

Monitoring selected high-risk behaviour indicators in groups at higher behavioural risk for 

HIV and STI should be strengthened with targeted behavioural surveillance surveys with 

integrated biological indicators in these groups. 


OP 7.1.1 

We can now avoid lipodystrophy/metabolic complications in newly treated 

patients ? PROS 


OP 7.1.2 

We can now avoid lipodystrophy/metabolic complications in newly treated patients? 

CONS 

I Poizot-Martin, Marseille, France 

ABSTRACTS 

The introduction of highly active antiretroviral therapy regimen since 1996 has 

significantly modified the course of HIV disease with longer survival rates but also longer 

exposure to antiretroviral molecules and to HIV itself. Given the current need for lifelong 

therapy, considerations of long-term toxicities such as hyperlipidemia and lipodystrophy 

are becoming increasingly important when choosing between different regimens. 

Important metabolic and cardiovascular differences exist between individual drugs within 

the same antiretroviral class and some of them seem to have a more favorable pattern of 

adverse effects. However, interactions between these drugs when there are associated in 

real life may appeared in the future. Thus, a long term follow up is still necessary to 

confirm the results of in vitro studies and those observed in clinical trials. Furthermore, 

about 30% of naive patients switch their therapy during the first year after initiation, and 

not always for a safe one. 

Several epidemiological studies have shown the association between antiretroviral 

therapy and cardiovascular risk. The increased risk of MI could not be only attributed to 

the lipid abnormalities associated with PI treatment. Indeed, this class has also been 

associated with endothelial dysfunction with differences between the different drugs within 

the class of PI. However, clinical significance for this toxicity has to be confirmed. 

Moreover, PIs also alter nuclear lamin A/C maturation and stability, which can also affect 

the cardiovascular system with a premature atherosclerosis. These laminopathies might 

also provoke an accelerated aging. Then HIV1 itself and gp120 may induce apoptosis of 

endothelial cells independently of PIs. Recently, several pharmacogenetic studies 

examined the relationships between genetic polymorphisms and changes in lipids and fat 

distribution. Although the results of these studies are not yet helpful for practical treatment 

strategies, they highlight the differences in individual susceptibility to drug effects. For all 

these reasons, avoiding lipodystrophy/metabolic complications in newly treated patients 

remains uncertain. 

OP 7.2.1 

Triple nRTI Combinations are Obsolete. PROS 


OP 7.2.2 

Triple nRTI Combinations are Obsolete. CONS 



OP 7.3.1 

We must switch early patients with detectable viremia 

PROS 

Yazdan Yazdanpanah 1,2 

1 

Service Universitaire des Maladies Infectieuses et du Voyageur, Centre Hospitalier de 

Tourcoing, 

2 

EA 2694, Faculté de Médecine de Lille, France 

Reduction in plasma HIV RNA below levels of detection is a primary marker of 

antiretroviral therapy success, generally leading to immune reconstitution, improved 

clinical outcomes, and limited emergence of mutations conferring drug resistance. Current 

treatment guidelines suggest that HAART should be changed after 2 consecutive HIV viral 

load measurements greater than 400 copies/mL if tolerable and effective treatment is 

available. 

Although clinical and immunologic benefits in treated patients may be maintained despite 

partial viral suppression (viral load

OP 7.3.2 

We must Switch Early Patients with Detectable Viremia 

CONS 

Rita Murri, Roma - Italy 

Achieving and maintaining viral suppression less than 50 copies/mL is the goal of current 

antiretroviral regimens. Current treatment guidelines suggest that HAART should be 

changed after 2 consecutive HIV viral load measurements greater than 400 copies/mL if 

tolerable and effective treatment is available. However, the threshold at which therapy 

should be switched to optimize patients' future prognosis is unknown. 

Even though the rationale for an early change of therapy in presence of a virological 

failure is related to the attempt to reduce the chance of developing drug resistance to the 

failing regimen, a switch in therapy poses new challenges for tolerability, adherence to a 

new regimen, and fit of therapy into the patient's daily routine. 

Indeed, despite published recommendations, it seems common in clinical practice that 

partial loss of viral suppression is tolerated without an immediate change in regimen, 

especially in patients who have limited therapy options. 

Several studies will be showed suggesting that even at detectable but moderate levels of 

HIV RNA the clinical progression of HIV infection is not significantly different from that of 

people with undectable viremia, particularly when HIV RNA was stable and below 10.000 

copies/ml. Risks of delaying a switch of therapy will be also discussed and are mainly 

related to the appearance of mutations conferring resistance to antiretroviral drugs. 

ABSTRACTS 

OP 7.4.1 

Entry inhibitors have to be spared for advanced stages. PROS 



OP 7.4.2 

Entry inhibitors have to be spared for advanced stages 

CONS 

Giuseppe Tambussi, Milano - Italy 

The various phase 2/3 clinical trials with CCR5 antagonists encompass both treatmentexperienced 

as well as naive HIV-infected individuals. Thus, future data will indicate 

whether chemokine receptor antagonists are best used as components of initial treatment 

regimen or reserved for use in later regimens. 

Unexpectedly, GSK announced it halted the studies with aplaviroc after a naïve patient, 

was found with elevated liver enzymes and bilirubin. Due to concerns that the drug may 

cause liver abnormalities, GSK discontinued all trials with aplaviroc, also those with 

treatment-experienced patients. Almost simultaneously, Schering-Plough announced the 

discontinuation of the studies with vicriviroc in naive patients. The decision was taken not 

due to hepatotoxicity, but after the return of detectable virus in some patients late in 

therapy compared to the control regimen of CBV plus EFV, a current standard of care for 

treatment-naive patients. However, Schering-Plough is continuing the phase 2 study with 

vicriviroc in US treatment-experienced patients which is conducted by the NIH-sponsored 

ACTG and is fully enrolled. 

Finally, the indipendent Data Safety Monitoring Board recommended that Pfizer 

discontinue the MVC 300 mg once-daily (QD) dosing arm in the treatment-naïve program 

(Study 1026), while continuing the other two arms of the study, MVC 300mg twice daily 

(BID) versus EFV 600mg QD, unchanged. The analysis of the first 205 patients given 

300mg of MVC QD in combination with AZT and 3TC (CBV) found that, after 16 weeks of 

treatment, the combination did not prove itself to be "non-inferior" to EFV, AZT and 3TC, 

a recognized standard of HIV care. 

Given the various challenges, it is questionable whether or not CCR5-targeted 

compounds will be the next partners of ENF, till now the only EI, in future antiretroviral 

therapeutic regimens. Big efforts have been put by pharmaceutical companies to yield 

small-molecule CCR5 antagonists. Will at least one of them make it through? 


OP 8.1 

Primate-to-Human Retroviral Transmission 

Lisa Jones-Engel 

University of Washington, National Primate Research Center, Seattle, WA, USA 

Gregory Engel 

Swedish Providence Family Medicine Residency, Seattle, WA, USA 

Nonhuman primates are important potential sources for emerging infectious diseases. 

Over the past decades political, social and economic forces have brought human and 

nonhuman primate populations into increasingly frequent contact, creating new contexts 

for interspecific pathogen transmission. However, given the emphasis placed on HIV/SIV, 

which has its origins in Africa, the issue of cross-species transmission in Asia and South 

America has been largely ignored. What is needed is a global assessment of the diverse 

contexts of cross-species pathogen transmission which takes into account the infectious 

agents, nonhuman primate populations, affected human populations and the diverse and 

complex manner in which the three interrelate. Our research group has studied 

bi-directional pathogen transmission between humans and nonhuman primates in Asia 

using a multidisciplinary approach. Asia is a particularly compelling setting for this type of 

research given the regions' plethora of nonhuman primate species and habitats that also 

contain a rich non-primate fauna. What's more, these dynamic primate populations and 

the infectious agents they contain are situated amidst the world's densest human 

populations (including a growing number of people immunocompromised by HIV and 

tuberculosis) in a region bustling with regional and international commerce, and a 

popular destination for tourists from around the globe. Beyond documenting interspecies 

viral transmission in Asia we are improving our ability to predict emerging primate 

zoonoses by using risk analysis models based on our field and experimental data. This 

work holds the promise of harnessing data to reduce the zoonotic risks to humans in 

contexts where humans and nonhuman primate contact occurs. 

ABSTRACTS 


OP 8.2 

West Nile Virus Infection in Humans: An Emergent Disease 

James J. Sejvar, MD 

Division of Vector-Borne Infectious Diseases and Division of Viral and Rickettsial 

Diseases 

National Center for Infectious Diseases - Centers for Disease Control and Prevention 

Atlanta GA USA 

West Nile Virus Infection 

West Nile virus (WNV), an arthropod-borne flavivirus, has historically been associated 

with infrequent epidemics of febrile illness in parts of Africa, Asia, and Europe. More 

recently, outbreaks of WNV have increased both in frequency and in disease severity. 

Since approximately 1996, epidemics and epizootics of WNV have occurred in Romania, 

France, Tunisia, Russia, and other European countries. However, the emergence and 

subsequent spread of WNV in North America has resulted in the largest outbreaks of 

arboviral encephalitis in the Western hemisphere, with a resultant expansion in our 

understanding of the clinical spectrum of human illness. 

Transmission of WNV involves mosquito vectors and birds as amplifying hosts; e 

xperience in North America has suggested great differences in vector competence, which 

can influence human disease burden. Natural infection in humans is acquired through 

bites from infected mosquitoes; however, several other modes of transmission have been 

recognized, including transmission through blood transfusions, organ transplantation, and 

transplacental transmission from infected mother to fetus. 

Approximately 80% of human infections with WNV remain clinically silent. Most 

symptomatic individuals develop West Nile fever, characterized by fever, chills, headache, 

and fatigue. Most people recover completely, although recent data suggest that some 

persons continue to experience persistent overwhelming fatigue. Non-neurologic clinical 

manifestations, including rhabdomyolysis, ocular disease, and myocarditis, have been 

described in case reports. More severe illness is seen in patients developing West Nile 

neuroinvasive disease (WNND), which includes meningitis, encephalitis, and a 

poliomyelitis-like syndrome. Elderly persons and immunocompromised individuals are at 

greater risk of developing WNND. West Nile meningitis is characterized by fever, 

meningismus, and headache; most persons recover uneventfully. West Nile encephalitis 

is characterized by altered mental status or other neurologic deficits, and may range in 

severity from a mild confusional state to severe encephalopathy and death. Movement 

disorders including positional tremor, myoclonus, and parkinsonism, are frequently seen. 

West Nile poliomyelitis is due to involvement of the lower motor neurons of the spinal cord, 

similar to the syndrome produced by poliovirus infection. It is characterized by acute, 

asymmetric weakness; brainstem involvement may result in acute neuromuscular 

respiratory failure, associated with high morbidity and mortality. Clinical outcomes of 

WNND vary, with some individuals experiencing persistent headaches, movement 

disorders, cognitive difficulties, and fatigue. In West Nile poliomyelitis, persistent long-term 

limb weakness and disability appear to be the rule. 

There is no definitive treatment for WNV disease. Several therapies, including interferon-, 

antisense nucleic acid agents, and antivirals, have either not been assessed in 

randomized clinical trials or have not shown promising results. An intravenous 

immunoglobulin product with high titers of anti-WNV antibodies is currently under 

investigation. Several vaccines are in development and are undergoing clinical trials. 

The future pattern of WNV in the Western hemisphere and elsewhere is unclear; 

however, heavy viral activity has been observed in North America for several consecutive 

years, lower level activity continues in several European countries, and WNV has been 

detected in Central America. This suggests that WNV will continue to be a source of 

considerable human morbidity and mortality for the foreseeable future. 


OP 8.3 

Epidemiology and Control of Avian Influenza 

Arjan Stegeman 

Faculty of Veterinary Medicine - Department of Farm Animal Health 

Introduction 

Infections with Avian Influenza (AI) viruses are common in various mammal and bird 

species. AI is a notifiable animal disease (OIE), and outbreaks of AI were reported for 

decades in several countries, such as Mexico, Italy, The Netherlands, and Canada. Until 

a few years ago, AI, or fowl plague, was mainly considered being a veterinary problem, 

causing high mortality in poultry and severe economic damage for the poultry industry. 

Since the outbreaks of high pathogenicity (HPAI) H5N1 in Asia in 1997, however, AI also 

attracted the attention of public health organizations, as this strain caused the death of 

over 100 persons, and multiple numbers distracted the infection. Scientists are warning for 

a new influenza pandemic, and nowadays, the disease seems to be more a human 

health issue than a veterinary one. 

ABSTRACTS 

It should not be forgotten, however, that, at least until this moment, the disease mainly 

affected poultry and other birds. Especially the poultry industry in Asian countries, like 

Thailand, Vietnam, Cambodia, Indonesia and others, is struck by AI epidemics. Everyone 

saw pictures of desperate farmers and their families, farms being depopulated, people 

carrying bags full of chickens and throwing them into pits. The outbreaks seemed to be 

limited to this part of the world, but last year, the virus also spread to countries in the 

western hemisphere, such as Russia, Turkey, Romania, Slovenia, Germany, France and 

many other. These outbreaks were controlled rather quickly and relatively few farms 

became infected. 

In addition to this, it should be realized that other HPAI strains than H5N1 may emerge, 

and may cause epidemics in poultry or a new human pandemic. This year, Europe only 

had localized outbreaks of H5N1, but three years ago, The Netherlands was confronted 

with a huge epidemic of H7N7, during which 30 million poultry were killed and one 

veterinarian died. So we know how devastating an AI infection for the poultry industry can 

be, and how large the impact is on the society. 

Because of the devastating effect for poultry and the possible public health risk, outbreaks 

of HPAI should be controlled as quickly as possible. From a veterinary perspective, but 

also from a human health point of view, the disease should be controlled at the source, 

i.e. the poultry farm. Especially, prompt reduction of the virus output is very important, with 

respect to reduction of the exposure for poultry and humans. 

Control of AI 

To stop epidemics of HPAI, knowledge of the effectiveness of the control measures 

implemented during an epidemic is of vital importance. Four issues that are logically 

related to the epidemiology of Avian Influenza will be addressed, mainly with respect to 

the Dutch epidemic. 


First, the origin of primary introductions of the virus into farmed poultry populations will be 

reviewed, and next the secondary transmission between poultry farms. Subsequently, the 

knowledge on the prevention of primary introductions and the control of secondary 

transmission will be addressed. 

Primary introductions 

Primary introductions of Avian Influenza virus in farmed poultry populations may originate 

from three sources: free flying aquatic birds, live poultry markets or pet birds. The relative 

risk associated with each of these sources varies depending on the likelihood of direct or 

indirect contacts with susceptible poultry. 

Until recently, the hypothesis was that free flying aquatic birds, especially ducks and 

geese, but also shorebirds, gulls, terns and auks, serve as an important reservoir of low 

pathogenicity AI virus strains (LPAI). These LPAI virus strains can be transmitted from 

waterfowl to poultry by infected feces either through direct contact or indirectly through 

contamination of feed, water, or free-range area. If the LPAI strain is of the H5 or H7 

subtypes, the next step would be that the virus mutates into a HPAI strain, causing an 

outbreak in poultry. 

Most of the introductions of H5N1 in Europe, are, however supposed to originate from 

migratory birds, either directly from Asian countries, or via an intermediate host. 

Since 1959 24 primary isolates of HPAI have been identified, and last year H5N1 was 

found in swans, ducks, geese and other water fowl in most of the countries of Western 

Europe. 

In addition to waterfowl, live bird markets also pose a significant risk to the introduction of 

AI viruses into poultry flocks. Because of the continuous marketing process, LPAI and, in 

Asian countries probably also HPAI virus, can persistently circulate in these systems. 

Indirect contacts through contamination of persons, equipment or vehicles could transmit 

the virus to industrial poultry flocks. Additionally, companion or pet birds may also serve 

as a source of infection, because AI viruses have been recovered from caged birds, 

usually during quarantine. However, transmission from this source to poultry has not been 

documented. 

Secondary transmission 

Once infected, birds excrete AI viruses from both the respiratory and the digestive tract. 

Thus, within a poultry house, bird-to-bird transmission is probably by aerosol and 

ingestion. Between flocks, infected poultry feces appear to be a most likely source of 

transmission, human-associated contacts being the main route. 

In several specific accounts strong evidence has implicated the movement of caretakers, 

farm owners and equipment, trucks and drivers moving birds or delivering food, and 

artificial inseminators in the spread of the virus. Birds or other animals which are not 

themselves susceptible to infection may also become contaminated and transmit the 

virus. Moreover, shared water or food could become contaminated and serve as an 

infection source. Finally, there is some evidence that windborne spread may have played 

a role amongst very closely situated farms and that flying insects could become 

contaminated with infected feces. Vertical transmission of HPAI viruses is unlikely, 

because AI viruses are embryo lethal. 


Knowing that waterfowl and live poultry markets are most likely the primary source of 

infection to the industrial poultry flocks, the question is how to prevent those introductions. 

Prevention of introductions 

Actually there is one word that covers the prevention measure and that is bio-security. 

However, that word is still kind of vague, so it should be made clear what is meant by this 

word. 

The basic means for the prevention of primary introductions of influenza viruses into 

poultry flocks is to minimize the direct and indirect contacts between birds in these flocks 

on the one side and wild water fowl, live bird markets and pet birds on the other side. 

Consequently, bio-security is the way to minimize the risk of the initial introduction of Avian 

Influenza viruses into commercial poultry flocks. 

ABSTRACTS 

The most important bio-security measures are: 1) poultry kept indoors, 2) only one 

species of poultry on the premises, 3) no pet birds on the same premises as commercial 

poultry, 4) all in - all out production system (reduces the risk of an endemic infection with 

LPAI viruses), 5) no items (such as ponds) that attract wild birds to the premises, 6) feed 

and drinking water for poultry is not accessible for wild birds, 7) poultry workers do not 

have access to other birds, 8) fence around the poultry house 9) only those persons that 

really need to be there are admitted to the poultry house, 10) persons change clothes and 

boots before entering the poultry house. 

In addition to preventing the introduction of AI viruses it is desirable to impose surveillance 

for antibodies or clinical signs of AI. Such a program may detect LPAI virus infection in 

commercial poultry before mutation to HPAI has taken place or can detect an introduction 

of HPAI as soon as possible, before it has spread to (many) other flocks. When adequate 

measures are taken in such a situation, an epidemic of HPAI may be prevented or at least 

minimized. 

Keeping poultry indoors in a way that wild birds cannot reach them and they cannot come 

into contact with feces of wild birds may be very difficult to achieve in traditional housing 

systems. Next it is important to keep no other birds on the premises, because they may 

serve as a source of infection, either directly or through contact with wild waterfowl. 

In addition an all-in all out production system is important. Actually this is not a measure 

to reduce the probability of introduction of the virus, but to stop the circulation of lowpathogenicity 

virus. Items, such as ponds, that attract wild birds increase the risk of virus 

introduction. The same is true for feed and drinking water if wild birds can access it. 

Moreover, poultry workers may introduce the virus by feces on their boots our clothing, or 

they may be infected themselves. Finally, it is wise to have stringent regulations for the 

admission of persons. Only those persons that really need to be there should have permission 

to enter the shed, and they should change clothes and boots before they enter 

the poultry houses. 

Control of secondary transmission 

The amount of virus produced by an infected flock can be reduced by the killing and removal 

of these flocks (culling). This approach is followed in most countries, for instance during 

the epidemics in Italy, the Netherlands (2003), countries in Asia and the US (e.g. 2003- 

2004). As farmers should be compensated financially, which is not always, feasible culling 

infected poultry is not always possible. 


To reduce the amount of virus that is transferred during contact persons must change 

boots and clothing upon entering the premises. Moreover, equipment that comes into 

direct contact with poultry or their feces should not be moved from farm to farm without 

adequate cleaning and disinfection. Cleaning of fecal material and disinfection of 

eggshells may be necessary to prevent the hatchery-associated dissemination of AI 

viruses (Swayne and Halverson, 2003). In addition, the contact rate between flocks and 

the number of flocks that make contact with each other should be minimized by measures 

such as a ban on the transport of poultry and poultry products, strict control of the 

movement of personnel and equipment. Furthermore, it is important to keep the traffic 

area near the poultry house from becoming contaminated with manure. 

The culling of infected flocks is often accompanied by depopulation (pre-emptive culling) 

of contiguous flocks. Some of these contiguous flocks may already have been infected 

and, consequently, will be depopulated when their infectivity is still low. Despite their 

rigorous nature, it is questionable whether these measures are sufficient to stop an 

epidemic in poultry dense areas and areas with many turkeys (Swayne and Halvorson, 

2003; Stegeman et al., in press). In such areas virus circulation may remain until all 

poultry flocks have been depopulated. Moreover, it is unclear in what area the farms 

should be culled. 

In the Netherlands, pre-emptive culling in an area of one kilometer around an infected 

flock was not sufficient, or could not be carried out quickly enough to prevent further 

spread of the infection. Only after the whole affected area was depopulated, the virus was 

eradicated. 

Another way to reduce the amount of virus produced by an infected flock is vaccination. 

Moreover, vaccination reduces the amount of virus necessary to infect a susceptible 

animal. Experimental studies have demonstrated that inactivated monovalent and 

polyvalent virus vaccines with adjuvants are capable of inducing antibodies and providing 

protection against mortality, morbidity and decline of egg production. Moreover, 

vaccination significantly reduces the excretion of virus (Boyle et al., 2000; Swayne et al., 

2001; Tollis and Di Trani, 2002; Di Trani et al., 2003), which may reduce virus spread in 

an infected area. However, in several countries, vaccines, designed to contain or prevent 

HPAI, are specifically banned or discouraged by government agencies, because they may 

interfere with stamping out control policies. It is argued that, since immunized birds are still 

able to become infected and excrete virus, the virus may continue to spread. In addition 

since immunized birds may not show clinical signs, infection may go unnoticed for long 

periods and even exacerbate the spread of the virus. However, most HPAI control 

regulations reserve the right to use vaccination, because a stamping out policy may be 

unsuccessful, unethical and, depending on the situation, not economically desirable. 

Because of the rare nature of HPAI, pre-emptive prophylactic vaccination on a large scale 

is not desirable. However, vaccination can be applied to establish a (large) buffer zone 

around an outbreak. As examples, vaccination was used during outbreaks of LPAI in Italy 

from 2000-2002 (Capua and Marangon 2003; Marangon et al., 2003), in Utah in 1995 

(Frame, 2000; Halvorson, 2002), and HPAI in Mexico and Pakistan in 1994 (Naeem, 1998; 

Arriola, 2000). It is important that the use of vaccination must be regarded as 

complementing strict bio-security, quarantine and other measures aimed at preventing 

spread of the virus. 


Concluding remarks 

To prevent new epidemics of AI the poultry industry should focus on minimizing the 

contacts between commercial poultry flocks on the one side and waterfowls, live bird 

markets and pet birds on the other side. Moreover, to stop future epidemics, movement of 

personnel and equipment must be strictly controlled and strict hygiene enforced. 

In addition, infected flocks need to be stamped out and contiguous flocks must be 

depopulated pre-emptively. The latter may, however, be insufficient in densely populated 

area, leading to a choice to either depopulate an entire area, or vaccinate all poultry in a 

buffer zone. In all cases it is essential to educate poultry workers regarding how viruses 

are introduced, how they spread, and how such may be prevented. 

ABSTRACTS 

OP 8.4 

Dengue Disease in the French West Indies. 



OP 9.1 

New Developments in the Treatment of Chronic Hepatitis B 

Stephanos J. Hadziyannis M.D. 

Professor of Medicine 

Athens, Greece 

Treatment of chronic hepatitis B (CHB) involves a number of complex and controversial 

issues. There are two major types of chronic hepatitis B, one with positive and the other 

with negative HBeAg, to which largely differing initiation criteria and end-points of therapy 

should be applied; their natural course is highly variable and frequently unpredictable; 

therapeutic options with currently approved and developing drugs differ significantly 

depending on the severity of liver necro-inflammation, the stage of fibrosis and on the 

functional capacity of the affected liver. In addition to these variables there are many other, 

yet unresolved, issues, including cost and long-term safety and resistance. Experts may 

have differing views regarding the best treatment approach and practicing clinicians have 

to find the way out in making, evidence-based treatment decisions appropriate for 

individual patients. In this presentation new developments in the therapy of chronic 

hepatitis B with emphasis on treatment strategies , first line/first choice drugs and 

treatment paradigms will be critically discussed. 

All hitherto approved drugs are considered as first line therapies both for HBeAg-positive 

and HBeAg-negative CHB. In general, finite courses of therapy in both types of CHB with 

interferon-alfa appear to be more efficacious compared to finite courses of n.analogues 

courses at least in terms of sustained virological response (SVR) rates. Notably, 

in HBeAg-negative CHB, SVRs are rarely achievable (30% of 

patients with compensated chronic hepatitis B. It is also becoming generally acceptable 

that if a patient does not respond to or cannot tolerate or is reluctant to IFN-alfa therapy, 

then n.analogue therapy should be applied. In the case of HBeAg-negative patients 

n.analogue therapy should be very long lasting aiming at effective on-therapy HBV 

suppression, maintained without development of drug resistance. However the end points 

and optimal duration of such long therapies have not been established as yet. 

The advantages and disadvantages, the weak and strong points of the approved and 

coming n. analogues will be further discussed. For the time being, the best long-term 

resistance profile has been documented in adefovir dipivoxil treatment. However, its cost 

is high and it is becoming clear that going monotherapy with any n. analogue cannot be 

expected to be free of long-term HBV resistance. The current evidence on the efficacy of 

combination therapies in treating lamivudine- or other nucleoside analogue-resistant HBV 

patients will also be reviewed. 


OP 9.2 

Improving anti-HCV therapy 

Stanislas Pol, MD, PhD 

Authors Affiliation 

APHP, Hôpital Necker-Cochin, Unité d'hépatologie, Paris ; Université Paris Descartes, 

Paris; INSERM U-567, Institut Cochin, Paris, France. 

The estimated prevalence of hepatitis C virus (HCV) infection is 2% representing 

123 million infected individuals worldwide. HCV-infection burdens public health in relation 

with hepatic (cirrhosis in 20% of patients and its complications) and extra-hepatic 

(vasculitis) complications and lessens quality of life. Major progresses have been made in 

the last two decades for diagnosis and treatment of HCV including: 1. more appropriate 

screening strategies for HCV infection (improved sensitivity of serological and virologic 

tests); 2. a better evaluation of the liver impact of chronic HCV infection (semiquantitative 

scoring systems of necro-inflammation and fibrosis on liver biopsy, 

non-invasive evaluation of fibrosis with biochemical markers and elastometry); 3. 

improved therapeutic regimens. They provide a better definition of: 1. who to treat 

(clinical impact or significant fibrosis); 2. how to treat : tailoring therapies for doses and 

durations of the pegylated interferon and ribavirin combination according to virologic 

factors (mainly genotype and early viral kinetics, but also baseline viral load) and hosts 

factors (fibrosis, immune status, weight...); 3. how to monitor efficacy and tolerance of 

therapy. Progresses have now resulted in a 50% rate of complete HCV eradication 

ranging from 45 to 90% according to the genotype and especially in those patients with 

early viral response. New therapies, specific HCV protease or polymerase inhibitors, will 

increase these encouraging results in a next future, in association with pegylated 

interferon or more potent and less toxic new formulations of interferons or ribavirin. 

Key words: Hepatitis C virus (HCV)/chronic hepatitis/cirrhosis/hepatocellular 

carcinoma/Interferon/Ribavirin 

ABSTRACTS 


OP 9.3 

Future options in non responders and relaspers after current anti HCV therapy 

Marc Bourlière, MD 1 

1 

Service Hépato-gastroentérologie, Hôpital Saint Joseph, Marseille, France 

Pegylated interferons in combination with ribavirin, allow viral eradication in 54-66% of 

treatment-naïve patients (1-5). Although the response rates seen with pegylated 

interferons plus ribavirin are substantially greater than with earlier therapeutic 

interventions such as conventional interferon mono- and combination therapy, a 

proportion of those treated still fail to achieve a sustained virological response (SVR). 

Thus, non-responders to prior antiviral therapy comprise a growing, and increasingly 

important population of hepatitis C patients. 

Natural history studies indicate that between 3-20% of individuals who remain infected 

with hepatitis C virus (HCV) will develop cirrhosis over a period of 20-25 years, and these 

patients are also at risk of developing end-stage liver disease and hepatocellular 

carcinoma. Eradication of HCV following successful therapeutic intervention has 

numerous benefits, including a reduced risk of progressive liver disease, regression of 

fibrosis, improved quality of life, and a reduced risk of HCV transmission to others. 

A lack of response to anti-HCV treatment can generally be categorised as either a 

complete non-response (where HCV RNA levels do not significantly decline by >2-log10 

throughout therapy), or virological relapse (where HCV RNA becomes undetectable 

during treatment but is detected again after discontinuation of therapy). 

Retreatment studies have generally shown a differing pattern of response among 

non-responders and relapsers, with relapsers showing a greater SVR rate than true 

non-responders. 

Non-response to treatment can be attributed to a number of potential factors, which fall 

into two broad categories. 

i) Therapeutic insufficiency. In this situation the dose of interferon and/or ribavirin, or the 

duration of treatment, have been inadequate and have failed to maintain sufficient 

antiviral pressure to eradicate HCV(6,7). 

ii) Virological resistance. Despite sufficient doses of interferon and ribavirin and an 

adequate duration of therapy, the patient remains HCV RNA-positive. Numerous host-, 

viral-, and disease-related factors have been shown to compromise the efficacy of 

anti-viral therapy (8). 

1) Retreatment of Patients Whose Non-Response is Attributed to Therapeutic 

Insufficiency 

There are a number of different factors which can contribute to the overall success, or 

failure, of initial anti-HCV treatment. While the majority of host-, viral- and disease-related 

factors associated with a reduced response rate cannot be modified, factors that 

contribute to 'therapeutic insufficiency' during initial treatment (such as the type of 

previous treatment, adherence and side effects) can be improved, and this should be 

considered prior to starting retreatment. 

Due to the increased SVR rate associated with pegylated interferons in treatment-naive 

patients, those who have failed to eradicate HCV with an initial course of conventional 

interferon mono- or combination therapy may benefit from retreatment with the newer, 

more effective pegylated interferon/ribavirin combination regimen (9-12). 


Such an approach has recently been investigated in the initial phase of the Hepatitis C 

Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial, in which previous 

non-responders to conventional interferon mono- or combination therapy were retreated 

with standard-dose (180 g/week) peginterferon alfa-2a (40KD) plus ribavirin (1000/1200 

mg/day) for up to 48 weeks (13). Patients who showed a virological response at week 20 

(35% of those analysed) continued with combination therapy, while patients with no 

virological response at week 20 were randomly assigned to continue with peginterferon 

alfa-2a maintenance monotherapy at a reduced dose (90 g/week) for an additional 3.5 

years, or no treatment (13). Among the first 604 patients enrolled in the study, 89% of 

whom were infected with HCV genotype 1, 18% overall achieved an SVR. As would be 

expected, the SVR rate was higher in those who had previously been treated with 

interferon monotherapy (28%) than in those who had failed interferon/ribavirin 

combination therapy (12%)(12). Similar response rates were observed in the EPIC-3 

study, which evaluated the efficacy of 1.5 g/kg peginterferon alfa-2b (12KD) plus a higher 

maximum dose of ribavirin (800-1400 mg/day) for 48 weeks in patients who had failed to 

respond or had relapsed with prior conventional interferon combination therapy(14). 

Among the first 575 patients analysed, an SVR was seen in 14% of non-responders and 

41% of relapsers(14). Although data from this large studies have only recently emerged 

and the likelihood of inducing an SVR with retreatment is relatively modest(12,14), other 

potential benefits such as regression of fibrosis and an improved quality of life should be 

considered as a good incentive to retreat, particularly among those at risk of fibrosis 

progression and those with a favourable patient and/or viral profile. A small study in 

previous non-responders to peginterferon alfa-2b (12KD) (n=31) retreated with 

peginterferon alfa-2a (40KD) 180 g/week plus ribavirin 1000/1200 mg/day showed an 

SVR rate of 32%, although these results should be interpreted with caution due to the 

small number of patients included(15). 

ABSTRACTS 

2) Retreatment of Patients Whose Non-Response is Attributed to virological resistance 

a) Retreatment with other drug combinations 

The efficacy of triple combination therapy regimens, whereby a third agent with a different 

mode of action is added to standard therapy, has recently been assessed among previous 

non-responders and those with 'difficult to treat' characteristics. Studies using a triple 

combination with amantadine (an antiviral agent) have generally shown a modest or no 

added benefit compared with standard therapy(16-21). However, a recent meta-analysis 

of 38 randomised studies suggested some benefit in previous non-reponders, but no 

noteable effect in treatment-naive or relapser patients (22). 

The use of new molecules such as thymalfasin (23,24), which has an immunomodulatory 

action, or high doses (15 µg/day) of interferon alfacon-1 (consensus interferon) (23) have 

been evaluated. A pilot study found that a combination of peginterferon alfa-2a (40KD) 180 

µg/week, ribavirin 800/1000 mg/day and thymalfasin 1.6mg twice weekly resulted in a 

48% virological response at the end of 48 weeks' treatment in patients not responding to 

conventional interferon/ribavirin combination therapy(24).Some study suggest that 

consensus interferon, which is a "consensus" molecule of the type 1 interferon with a 

higher biological activity in vitro may be more effective than standart interferon for 

interferon non responders. Moreover several pilot studies suggested that combination 

therapy with high-dose daily induction consensus interferon with ribavirin increased early 

virological response rates and can achieve a sustained viriological response rate between 

26 to 45% in non responders patients to standard interferon and ribavirin depending on 


the consensus interferon dose (25,26). A recent randomized open-label pilot study 

demonstrated that daily consensus interferon plus ribavirin in non responders patients to 

interferon and ribavirin had an early virological response rate of 82% and a sustained 

virological response rate of 22% (27). In this study, induction dosing resulted in a greater 

first phase HCV-RNA decay that, however, did not translate to better sustained virological 

response rate , presumably due to more dose modification. The combination of high-dose 

interferon alfacon-1 (15 µg/day for 12 weeks then 15µg three times weekly for 36 weeks) 

and ribavirin (800/1000 mg/day) in pegylated interferon combination therapy 

non-responders was associated with a 43% end of treatment virological response and a 

37% SVR(28). In another pilot study, the combination of high-dose interferon alfacon-1 

(15 µg/day) and interferon gamma-1b (50µg three times per week) in a similar 

non-responding group led to a virological response at the end of treatment in 44% of 

patients (48% in genotype 1 patients)(23). 

Exploratory triple combination therapy studies using mycophenolate mofetil (an 

immunosuppressant which acts by potent inhibition of inosine monophosphate de 

hydrogenase and is commonly used in the transplantation setting) have failed to 

demonstrate any significant increase in the SVR rate compared with standard therapy 

among previous non-responders or relapsers (16,29) 

b) Longer treatment durations and higher doses 

Other strategies currently under investigation to improve upon the current SVR rates seen 

in retreatment include the use of a higher dose of pegylated interferon and/or ribavirin, and 

extension of the treatment duration to beyond the 48-week maximum currently 

recommended. 

The efficacy of high induction doses of peginterferon alfa-2a (40KD) has recently been 

evaluated in a randomised, phase II study involving 72 patients with HCV genotype 1 

infection who had failed to respond to previous conventional interferon plus ribavirin (10). 

In this trial, high induction doses of peginterferon alfa-2a (40KD) (360 or 270 µg/week for 

the first 12 weeks, followed by standard dose for 36 weeks) plus ribavirin produced an 

EVR in 46 and 35% of patients, respectively, compared with only 21% in patients who 

received standard-dose peginterferon alfa-2a (40KD) plus ribavirin. At week 72, respective 

SVR rates were 38% and 30% vs 18%. Data from the TARGET trial, which assessed a 

high dose of peginterferon alfa-2b (12KD) (3.0 g/kg/week) plus ribavirin for 48 weeks, 

compared with a standard dose of 1.5 g/kg/week plus ribavirin, in HCV genotype 1 

non-responders or relapsers (to conventional interferon mono- or combination therapy) 

demonstrated that administration of high-dose peginterferon alfa-2b (12KD) led to a 

sustained virological response rate of 25% in previous relapsers and 14% in previous non 

responders. The SVR rate was also different according to previous regimen : 25% of SVR 

rate in patients treated with conventional combination therapy and 15% in patients treated 

with pegylated combination therapy. Finally, outcomes from a randomised pilot study 

indicate that higher doses of peginterferon alfa-2b (12KD) administered on a twice-weekly 

basis may improve SVR rates in difficult-to-treat patients, when compared with a standard 

weekly dosing regimen. The differences, however, were not statistically significant in 

non-responder patients(30). 

To our knowledge, there is a lack of published data on the potential benefits of extending 

the duration of treatment for previous non-responders, although this is currently under 

investigation (31). However, evidence from the treatment-naive population has indicated 


that extension of the treatment duration to 72 weeks in genotype 1 patients reduces the 

risk of relapse compared with a standard (48-week) treatment duration.(32). Improved 

response rates were also seen in recent study where patients without an RVR at week 4 

underwent an extended duration of treatment (33). The results of studies investigating a 

longer treatment duration among previous non-responders are awaited with interest, 

particularly among the population of relapsers. 

An ongoing international trial evaluating REtreatment with PEgasys in pATients not 

responding to prior peginterferon alfa-2b/ribavirin combination therapy (REPEAT), is 

currently underway. The study, which evalutes four different retreatment approaches, will 

assess whether a high fixed-dose 12-week induction regimen of 360 g/week 

peginterferon alfa-2a (40KD) combined with ribavirin, treatment extension beyond 48 

weeks, and a high fixed-dose induction coupled with a longer treatment duration, are 

associated with a greater SVR rate than a standard dose of peginterferon alfa-2a (40KD) 

(180 g/week) plus ribavirin given for the standard duration of treatment (48 weeks)(31). 

The study will provide a long-awaited insight into whether patients who have failed to 

eradicate HCV with pegylated inteferon combined with ribavirin can benefit from 

retreatment with a different drug from the same therapeutic class. Preliminary results at 

week 12 suggest a higher rate of early virological response with induction dose (60%) as 

compared to standard dose (42%). A similar study that is designed to evaluate the 

efficacy and safety of peginterferon alfa-2b plus ribavirin in patients who either did not 

respond or relapsed following treatment with peginterferon alfa-2a (40 KD) and ribavirin is 

also underway. 

ABSTRACTS 

Maintenance therapy 

Despite the overall modest SVR rate reported to date in the retreatment of non-responders, 

it is important to consider other potential benefits associated with pegylated interferon 

therapies. It has been shown that although histological improvement generally occurs to 

a greater extent in those achieving an SVR, patients who fail to eradicate HCV may still 

experience an improvement in liver histology (21,34-36). As the primary aim of treating 

chronic hepatitis C is to reduce the risk of liver-related morbidity and mortality, histological 

improvement should be considered an important goal in all patients, especially those with 

advanced fibrosis or cirrhosis who may have failed to achieve an SVR during initial 

treatment. 

Maintenance therapy, which utilises drugs with an antifibrotic action over a long treatment 

duration, has thus become the focus of a number of clinical trials. The objective of 

maintenance therapy is to delay, or even reverse the progression of hepatic fibrosis, thus 

preventing cirrhosis and its associated complications(12,14, 37). Due to the long duration 

of therapy, this approach should be reserved for patients with significant fibrosis or 

cirrhosis. If a patient has previously failed to respond to conventional interferon-based 

therapy, and retreatment with pegylated interferon combination therapy at the correct dose 

and duration has been unsuccessful, then maintenance therapy should be considered. 

Early studies evaluating the potential benefits of maintenance therapy in non-responders 

provided the first indication that prolonged administration of interferon monotherapy may 

prevent histological progression of chronic hepatitis C among patients who remain 

viraemic (38). Clinical trials are currently underway to explore the effect of pegylated 


interferon maintenance therapy in delaying the serious hepatic complications associated 

with chronic HCV infection. 

An interim analysis of the COPILOT trial, which compares long-term maintenance 

therapy of peginterferon alfa-2b (12KD) with colchicine maintenance therapy, has 

indicated that complications of cirrhosis such as portal hypertension are less frequent in 

patients treated with peginterferon alfa-2b (12KD)(37). 

Drugs which possess fibrolytic properties, and those that supress fibrogenesis may also 

be good candidates for HCV maintenance therapy. A range of molecules has been 

investigated in vivo, although few have been used in patients with chronic hepatitis C. 

These agents possess varied mechanisms of action and target different stages of 

fibrogenic cascade. Thus, combination therapy with different antifibrotic agents may serve 

to increase the overall antifibrotic action during maintenance therapy, and is likely to be a 

focus of future study. 

The few antifibrotic agents studied to date in patients with chronic hepatitis C have shown 

early promise, but further studies are needed before an accurate assessment of their 

benefit can be made. Interleukin-10, a cytokine that down-regulates the 

pro-inflammatory response and has a modulatory effect on hepatic fibrogenesis, produced 

normalisation of transaminases, improved liver histology, and reduced liver fibrosis in a 

large proportion of non-responders to interferon-based therapy (39); but a larger 

unpublished study was completely negative and severe safety issues occurred. Several 

trials coordinated by the Agence Nationale de Recherches sur le SIDA, the French Agency 

for AIDS and Hepatitis, have been conducted using vitamin E, and a number are ongoing 

with vitamin E alone or in combination with pentoxifylline and an angiotensin II receptor 

antagonist. In a randomised study of 120 patients with chronic hepatitis C not responsive 

to interferon alfa, oral supplementation with N-acetyl cysteine and vitamin E did not 

improve the efficacy profile of interferon alfa retreatment (40). Administration of vitamin E 

failed to improve liver function, suppress hepatocarcinogenesis, or improve cumulative 

survival in another pilot study in patients with chronic hepatitis C (41). 

The Future Role of New Antiviral Agents in the Management of Non-response 

A range of promising new molecules are currently in development for the treatment of 

chronic hepatitis C. Among these, albuferon, an albumin/interferon-alfa fusion protein (42), 

merimepodib (VX-497), an orally administered inhibitor of the enzyme inosine 

monophosphate dehydrogenase (IMPDH) (43) and HCV polymerase inhibitors such as 

valopicitabine (44), have all shown early promise in clinical development trials. In addition, 

protease inhibitors such as VX-950 and SCH 503034 which are designed to block HCV 

replication are now being investigated in clinical trials (45,46). These molecules are 

clearly effective either alone or in combination with the current treatment of choice which 

will probably reduce the risk of early resistance; large randomised studies are now in 

progress. It is also likely that these agents will find a priority place in populations of 

previous non-responders to pegylated interferon/ribavirin therapy. 

Summary and Recommendations 

As previously described, non-response is known to be largely related to two main factors: 

1) therapeutic insufficiency; and 2) virological resistance attributed to the presence of one 

of more negative pronostic factors. For patients whose non-response is attributed to 

insufficient initial therapy, given the increasing level of supportive evidence, retreatment 

with peginterferon plus ribavirin seems an appropriate strategy in the management of 

chronic hepatitis C. Although retreatment studies to date have reported modest SVR rates, 


the current focus of research is to evaluate more agressive therapeutic strategies with a 

view to enhancing the response to retreatment. These studies will provide direction as to 

whether the use of higher interferon doses, a longer duration of treatment, or a 

combination of both increased dose and treatment duration, can enhance the response 

rates currently seen. Finally, in the next 1-2 years, a clearer picture will begin to emerge 

to determine the role of pegylated interferon maintenance therapy in the prevention of 

cirrhosis and its associated complications (12,14, 37), and new data will be available with 

the new antiviral agents. 

. 

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RebetronTM therapy: A report of two randomized, multicenter, efficacy and safety studies. Hepatology 2001;34: 243A. Abstract 77. 

30) Lodato F, Azzaroli F, Brillanti S, Colecchia A, Tame MR, Montagnani M, et al. Higher doses of peginterferon alpha-2b administered 

twice weekly improve sustained virological response in difficult-to-treat patients with chronic hepatitis C: results of a pilot randomized 

study. J Viral Hepat 2005;12: 536-42. 

31) Jensen DM, Marcellin P. Rationale and design of the REPEAT study: a phase III, randomized, clinical trial of peginterferon alfa-2a 

(40 kDa) plus ribavirin in non-responders to peginterferon alfa-2b (12 kDa) plus ribavirin. Eur J Gastroenterol Hepatol 2005;17: 899- 

904 

32) Berg T, von Wagner M, Nasser S, Sarrazin C, Heintges T, Gerlach T, et al. Extended treatment duration for hepatitis C virus type 

1: comparing 48 versus 72 weeks of peginterferon-alfa-2a plus ribavirin. Gastroenterology 2006;130: 1086-97. 

33) Sanchez Tapias JM, Diago M, Escartin P, et al. Sustained virological response after prolonged treatment with peginterferon alfa-2a 

and ribavirin in treatment-naive patients with chronic hepatitis C and detectable HCV RNA after week 4 of therapy: TERAVIC study 

[abstract]. J Hepatol 2004;40: 150. Updater Gastroenterology 2006; in press. 

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hepatitis C and cirrhosis. N Engl J Med 2000;343: 1673-80. 

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C who have sustained response to interferon therapy. Ann Intern Med 2000;132: 517-24. 

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SYS®) plus ribavirin (COPEGUS®) in patients with HIV-HCV co-infection: results of the AIDS PEGASYS Ribavirin International Coinfection 

Trial (APRICOT). Hepatology 2004;40 (Suppl 1): 241A. Abstract 174. 

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from the copilot study [abstract]. J Hepatol 2005;2005: Suppl. 2. 

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interferon therapy for patients with chronic hepatitis C virus and persistent viremia. Gastroenterology 1999;117: 1164-72. 

39) Nelson DR, Lauwers GY, Lau JY, Davis GL. Interleukin 10 treatment reduces fibrosis in patients with chronic hepatitis C: a pilot trial 

of interferon nonresponders. Gastroenterology 2000;118: 655-60. 

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hepatitis C not responsive to alpha-interferon alone: a randomized, multicentre study. Eur J Gastroenterol Hepatol 1999;11: 1203- 

7. 

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of hepatocellular carcinoma in patients with liver cirrhosis. Int J Vitam Nutr Res 2003;73: 411-5. 

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based therapy for chornic hepatitis C infection ( abstract) . J Hepatol 2006; 44: S51. 

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Antivir Ther 2005;10: 635-43. 

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Afdhal N, Rodriguez-Torres M, Lawitz E, et al. Enhanced antiviral efficacy for valopicitabine plus Peg-interferon with hepatitis C patients 

with HCV genotype 1 infection: results of a phase IIa multicenter trial [abstract]. J Hepatol 2005;42: 39-40. 

45) Reesink HW, Forestiuer N , Weegink CJ, et al. Initial results of a 14 day study of the hepatitis C virus inhibitor protease VX950 in 

combination with peginterferon alpha 2A (abstract). J Hepatol 2006; 44: S272. 

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with Peg-IFNanon-responders: antiviral activity and HCV variant analysis. J Hepatol 2006;44. Abstract 78. 


OP 9.4 

Antiretroviral agents in HIV-infected patients with cirrhosis 

Salmon-Ceron D, Sogni P, Taburet AM. 

Universite Paris V, Faculte Cochin, Service de Maladies Infectieuses, Hospital Cochin, 27 

rue du Faubourg Saint Jacques, 75014 Paris. dominique.salmon@cch.aphp-paris.fr 

Coinfection with HIV and hepatitis B or C viruses results in accelerated liver damage as 

compared with persons with chronic viral hepatitis alone. 

The use of HAART has led to significant improvement of hepatic related mortality and 

survival. However effective HAART use may also contribute to liver disease impairement 

by the hepatic toxicity of these drugs. 

The long term impact of some reverse transcriptase inhibitors (NRTI), although non metabolised 

by the liver, may be particularly severe on hepatic mitochondria leading to 

steatosis. 

Other classes such as HIV-1 protease inhibitors (PI) and non nucleoside reverse 

transcriptase inhibitors (NNRTI) are metabolized by the hepatic CYP enzymes and may 

accumulate in case of cirrhosis. This raises the possibility of significant interactions 

between antiretroviral medications and hepatic impairment induced by chronic viral 

hepatitis. Although the data are limited, the pharmacokinetics of several antiretroviral 

medications have been shown to be significantly altered in the presence of liver disease. 

Moreover, the relation between high antiretroviral concentrations and toxicity has been 

clearly demonstrated with certain PI and NNRTI. Further more, most PI have been 

associated with hepatic abnormalities, hyperlipemia and decrease insulin sensitivity, 

which themselves have been linked with hepatic steatosis. 

Although it is possible to initiate an antiretroviral at the standard dose in patients with 

cirrhosis (the therapeutic margin with antiretrovirals is wide), dose adjustment and 

therapeutic drug monitoring are useful particularly with PI and NNRTI, to adjust the dose 

and avoid adverse events. It is also recommended that the most hepatotoxic drugs be 

avoided, notably didanosine, didanosine+stavudine, nevirapine, and full-dose ritonavir. 

ABSTRACTS 


OP 10.1 

Progress in Microbicide Development 

Dr. Zeda Rosenberg, CEO, International Partnership for Microbicides 

AIDS is the world's most deadly infectious disease, claiming more than three million lives 

annually. Every day 14,000 people are newly infected by HIV, the virus that causes AIDS. 

Women and girls bear a severe and increasingly heavy burden in the AIDS epidemic - in 

sub-Saharan Africa, 57 percent of adults living with HIV are women. 

Women's susceptibility to HIV infection results from a combination of biological, social and 

cultural factors. Many women have little or no control over the conditions under which they 

have sex and often cannot negotiate the use of condoms. The limits of condoms, as well 

as other prevention methods, illustrate the urgent need for an expanded range of new 

prevention options, particularly ones that women can initiate like microbicides. 

Microbicides are products that could be used vaginally to reduce the transmission of HIV 

during sexual intercourse. Microbicides could take the form of a gel, cream, film, 

suppository or sponge that releases the active ingredient gradually. New delivery systems 

for microbicides are also being investigated, such as vaginal rings, novel controlledrelease 

technologies and solid dosage forms. 

First-generation microbicides are currently in large-scale efficacy testing. Researchers are 

also working on a next generation of microbicides which are specifically active against 

HIV, including using antiretroviral drugs (ARVs). The future of microbicides will likely be 

combinations - two or more mechanisms of action put in one product to increase 

effectiveness. Different mechanisms of action for ARVs include non-nucleotide reverse 

transcriptase inhibitors (NNRTIs), entry inhibitors that bind directly to HIV and render it 

unable to adhere to the cell, and CCR5 blockers that are designed to prevent HIV from 

efficiently entering host cells. 

One of the major challenges faced by the microbicide field is expanding the pipeline of 

candidate microbicides being tested. The field must continue to seek out innovative new 

compounds to prevent HIV, and facilitating licensing agreements with pharmaceutical 

companies is a key step in this process. Other challenges the field faces include 

managing clinical trials in developing countries, increasing funding for research and 

development, and encouraging international leadership to support the need for 

microbicides as part of a comprehensive response to HIV/AIDS. With leadership, sufficient 

financial resources, collaborative efforts and product development expertise, women in 

developing countries could have access to effective microbicides within the next five to 

seven years. 


OP 10.2 

HIV Vaccine Research : Challenges and Difficulties 

Marc P. Girard, Lyon - France 

The history of the AIDS pandemic is now well into its third decade. Tremendous progress 

has been made in our understanding of the complex interaction between HIV and the host 

immune response. Potent antiviral drugs have been developed that can control virus 

replication. However, many basic questions related to the feasibility of developing an HIV 

vaccine still remain unanswered, such as the identification of protective immune 

mechanisms, the design of envelope immunogens able to elicit virus-neutralizing 

antibodies with broad specificity against primary virus isolates, how to address the high 

variability of the virus and its remarkable ability to evade immune responses through 

escape mutations, just to name a few. At this time, the attention of the AIDS vaccine field 

has focused on the induction of HIV-specific cellular immune responses, especially CTL, 

in the hope that such a response would enable the vaccinated persons to better control 

their virus load following infection, slow down or even prevent their progression to clinical 

AIDS and decrease the probability of secondary transmission. This hypothesis, however, 

has so far received only little confirmation in the SIV/macaque model, where virus control 

following vaccination and challenge often appears to be short-lived, ultimately leading to 

vaccine failure. We will review some of the challenges to be met in the development of an 

efficacious HIV vaccine candidate, including the need to induce an immune barrier at the 

site of the genital, rectal and intestinal mucosae to prevent HIV infection. 

ABSTRACTS 


OP 10.3 

Current Advances in HIV Vaccine Development 

Patricia D'Souza, NIAID, NIH, USA 

Approximately 40 million people worldwide are living with HIV/AIDS. In 2005, an estimated 

5 million people worldwide were newly infected with HIV. Although an HIV vaccine 

remains the best hope for preventing new infections, it must be viewed as part of a multipronged 

approach that complements other prevention and treatment strategies to decrease 

HIV-1 transmission. An ideal vaccine should induce both cellular immunity and broadly 

reactive neutralizing antibodies. Recent scientific advances which have aided HIV-1 

vaccine development include an improved understanding that mucosal tissues are major 

sites for early viral replication as well as an increased understanding of HIV envelope 

structure. On the clinical front HIV vaccine pipeline is stoked with innovative vector-based 

vaccine strategies that encompass multi-genes from multi-clades. Vaccine trials are being 

conducted in a global network using validated laboratory measurements that enable 

simultaneous measurement of multiple T cell vaccine-induced immune responses in 

humans. Two vaccine strategies that successfully elicit HIV-1 CTL in humans use replication-incompetent 

adenovirus vectors with or without recombinant DNA priming are 

ongoing or close to starting in Phase II "test of concept" trials. Ultimately, the availability 

of an effective HIV vaccine will require the cooperation and collaboration of the global 

community to address key scientific roadblocks, manufacture clinical grade vaccines and 

expand clinical trials capacity. 

OP 10.4 

Updated data on DermaVir 



PP 1.1 

Hospitalization of Extra-European Union Children. A Five-Year Survey from 

Bologna, Northern Italy 

Roberto Manfredi 1 , Elena Baldi 2 , Sergio Sabbatani 1 

1 

Infectious Diseases, University of Bologna, Italy 

2 

Hygiene and Public Health, University of Bologna, Italy 

Introduction 

Since mid-eighties,unexpected migration waves involved Italy,regarding an estimated 

number of three million people,with around 400,000 of them remaining for a long period in 

a clandestine status.Methods.To assess all hospitalizations performed at our tertiary care 

Hospital from 1999 to 2004,involving extra-European Union (EU) children aged 

dysmetabolic, functional, or organic disorders (24.7%), followed by genetical-congenital 

diseases (15.7%), and infectious-parasitic illnesses (13.5%).Medical-dysmetabolic 

disorders occurred more frequently in children from EE (41.5%), followed by clandestines 

(24%), and children from Northern Africa (14.1%). Among infectious disorders,10 cases of 

tuberculosis, four of hepatitis B, and three cases each of HIV infection and syphilis, were 

detected. As a characteristic of the pediatric facilities of our Hospital,14.4% of admissions 

were due to pediatric malignancies, and 9.1% were directly linked to the delivery of 

chemotherapy-radiotherapy. 

Conclusions 

Our preliminary assessment showed rapid modifications of health care assistance of 

extra-EU immigrated children, during the past six years (1999-2004), while profound 

differences are evident according to patient's age, gender, and related disorders, and the 

condition of regular or clandestine immigrants. 


PP 1.2 

AIDS Orphans: Assessment of families in Crisis 

Megan Gatlin, Terry Le, Sharon Brown Kunin M.S., Eiman Mahmoud MD, MPH 

Touro University, Vallejo, CA, USA 

Introduction 

Currently, there are 14 million children who have lost 1 or both parents due to AIDS and 

80% are living in sub-saharan Africa. In 2015, it is estimated that rates will rise to 25 

million AIDS orphans. In Tanzania alone, there were nearly 1 million orphans in 2003. 

Typically these children are absorbed into extended families, which are already 

overwhelmed by poverty and therefore unable to provide adequate health care and 

education. 

Objective 

To conduct a needs assessment in a rural village of Tanzania & determine the factors that 

put orphans & their caregivers at risk for poor health and life outcomes. 

Methods 

Forty-four head of households and forty-nine orphans, living in the Ngorogoro village of 

the Lake Victoria region of Eastern Tanzania, were interviewed for this study. Participants 

were identified and recruited by village administrators. Two investigators plus a translator 

traveled by foot to interview villagers with surveys consisting of closed- and open-ended 

questions translated into Swahili. Responses were collected and entered into a database 

for analyses. The interviews were approximately 30 minutes and were conducted at 

designated locations or participants' home. 

Results 

Demographics: 

Females comprised over 80% of head of households. Mothers and grandmothers were 3 

times more likely to assume the responsibility of caring for orphans compared to other 

relatives. Seventy-five percent of caregivers surveyed completed primary school but less 

Orphans 

Forty-three percent of the orphans had lost both parents to HIV/AIDS. The average age of 

orphans surveyed was 12. The average age of a child when their parent(s) died was 6. 

Eighty-five percent of orphans attended primary school; however, only 1/3 of eligible 

orphans attended secondary school. 

Conclusions 

The HIV/AIDS epidemic is wiping out a whole generation of people and the economic and 

socio-emotional burden on families, especially those living in rural villages, is enormous. 

The greatest unmet need identified through this study was the lack of educational 

assistance, as 98% of families absorbing these orphans receive no financial help. Many 

children orphaned become caregivers and are made to work instead of attend school, 

thereby perpetuating the cycle of poverty and poor health outcomes. 

Future directions 

We envision that future medical students returning to the region will help develop & 

implement programs, in conjunction with community leaders, based on our preliminary 

findings. The development of micro-grants for women and/or educational vouchers may 

help families become more self-sufficient and allow children to stay in school. In addition, 

comprehensive HIV/AIDS-related prevention and educational programs may help 

decrease the rates of AIDS orphans. 


PP 1.3 

Immigration and HIV Infection in Northern Italy. Inpatient Admissions, 2000-2005 

Roberto Manfredi, Leonardo Calza 


Introduction 

Immigration is a recent phenomenon in Italy, mainly caused by the sudden and 

unexpected arrival of wawes of foreign citizens, refugees, and individuals escaping from 

war. This phenomenon is of great concern due to its serious socio-economic, cultural, and 

health care impact. 

Methods 

A prospective survey of all charts of patients (p) hospitalized or followed on day-hospital 

(DH) basis at our Infectious Disease ward until end-2005, allowed us to assess the 

frequency of admission of immigrants from extra-Western Europe (eWE), and to analyze 

multiple variables related to epidemiologic-clinical features. 

Results 

The rate of p immigrated from eWE showed a significant increase among our inpatients, 

and at a lesser extent and later for DH admissions: 7.7% and 3.1% during the year 2000, 

10.1% and 4.6% in 2001, 13.2% and 6.2% in 2002, 17.9% and 7.9% in 2003, 21.3% and 

8.9% in 2004, up to 17,7% and 10,8% in the year 2005 (p

PP 1.4 

Pradip Timilsena, Laxmi Prasad Wosti & Dewakar Paudayal 

Out reach Coordinator, Programme Officer & Programme Manager respectively; 

Kathmandu, Nepal 

This study establishes a link between poverty, migrant labour & HIV/STIs, in Achham 

District, a poor & remote area of Nepal. 

Methods 

This methodology involved quantitative & qualitative techniques as well as medical 

examination & testing (Hepatitis, B. Syphilis, HIV for 316 participants. 

Result 

Poverty is the main factor for sampled workers to migrate. However, the poverty 

differential between migrant & non-migrant is very small, & as a consequence migration is 

likely to increase with even slight economic shocks (as the most common coping 

strategy). Each family has one migrant member. Migration happens to places of high HIV 

incidence (e.g. Delhi, Mumbai & abroad countries). Both migrant & non -migrant 

respondents has a low prevalence of HIV (a prevalence of 0.33% among the sampled 

population 0 -3.9 % in 95 % ). However, migrants are also high - risk group with high 

prevalence of Syphilis & risky sexual behaviour. 

Conclusions 

The HIV pandemic is only at its starting point in Nepal, but the high migrant rate & the risky 

sexual behaviour of the migrants in places of high incidence of HIV can support an 

exponential increase. Preventive policy targeting migrants, if properly funded & 

implemented, can prove life saving & cost effective. 


PP 1.5 

Rapid shift from HIV-2 to HIV-1 in police officers in Guinea-Bissau, West Africa 

H Norrgren 1 , F Månsson 2 , AJ Biague 3 , ZJ da Silva 3 , S Andersson 4 , F Dias 3 , 

R Thorstensson 5 , M Jansson 6 , E-M Fenyö 6 

1 

Division of Clinical and Experimental Infection Medicine, Department of Clinical Sciences, 

Lund University, Lund, Sweden 

2 

Infectious Diseases Research Unit, Department of Clinical Sciences, Malmö, Lund 

University, Sweden 

3 

National Public Health Laboratory, Bissau, Guinea-Bissau 

4 

Department of Clinical Microbiology, Örebro University Hospital, Sweden 

5 

National Institute for Infectious Disease Control, Stockholm, Sweden 

6 

Division of Medical Microbiology, Department of Laboratory Medicine, Lund University, 

Lund 

Objective 

To evaluate trends of HIV-1 and HIV-2 between 1990-2005 in an occupational cohort of 

police officers in Guinea-Bissau. 

Methods 

An open cohort of police officers in Guinea-Bissau was formed in 1990, and up to the end 

of 2005, 4059 subjects have been included. 12.1 % were women. Clinical examinations 

and testing for antibodies to HIV were performed annually. In June 1998 there was an 

out-break of a civil war in Guinea-Bissau that lasted for almost a year. During the war 

period no testing was possible, but in July 2000 the inclusion of new individuals could 

continue. To evaluate changes in the prevalence of HIV in the police cohort, the study 

period was divided in six time periods, 4 periods before and 2 periods after the war. 

Results 

The prevalence of HIV-1 at the time of inclusion increased from 0.6% 1990-1991 to 10.2% 

in 2004-2005 (including HIV-1+HIV-2 dually reactive subjects). Conversely, the 

prevalence of HIV-2 declined from 13.3% to 6.2% over the same study period. When 

divided in age groups, subjects in the age group 35-44 years showed the most 

pronounced increase of HIV-1 prevalence before and after the war, from 3.9% 1996-1998 

to 13.0% 2000-2003. In 2004-2005 the prevalence of HIV-1 had further increased to 

14.2% in this age group. The age group 18-24 showed the slowest increase of HIV-1 over 

the study period, and in 2004-2005 the prevalence was 6.4%. In the same time period and 

age group the prevalence of HIV-2 was 0.7%. 

POSTERS 

Conclusions 

The prevalence of HIV-1 had started to increase already before the civil war in Bissau with 

doubling of the prevalence every second year (dually reactive subjects included). After the 

war the prevalence of HIV-1 has further increased and is now >10%. The prevalence of 

HIV-2 has gradually decreased, and in the youngest age group only 0.7% were infected 

2004-2005. The rapid shift from HIV-2 to the more virulent HIV-1 calls for a strong and joint 

effort in Guinea-Bissau to prevent further spread of HIV-1. 


PP 1.6 

Epidemiological aspects of Morbus HIV in the Region Nis-Serbia 

Branislav Tiodorovic&Jelica Tiodorovic 

Prof dr;Prof dr; Faculty of Medicine,Institute of Public Health,Clinic of Dermatovenerology 

Nis,Serbia Serbia and Montenegro 

Background 

Epidemiological characteristics of the HIV inficted disease in the Region Nis (South-East 

Serbia) 

Methods 

They were analysed on the Institute of Public Health based on the seropositivity prevalence 

in certain population groups and cases of the disease were registered. 

Results 

In the period from 1987 to 2005, with seroepidemiological investigations of HIV infection 

in the Region of Nis, worked up were 284000 serums (around 252000 samples of blood 

donors volunteers in the Blood Transfusion Center and 32000 samples in the Institute of 

Public Health in the Nis). There were 52 AIDS affected and 40 HIV positive persons (up 

to the present,40 death cases). Most of these were individuals aged 20-49 years (64,7%) 

and the most probable ways of transmission were homo/bisexual (23,9%), heterosexual 

(23,2%), contacs and intravenous narcotism (16,5%). Wives of two HIV positive males 

remained HIV negative up to the present. There were 73,8% males among the HIV 

positive and diseased persons,but the female proportion is constantly increasing. The 

linear tendency of the diseased is slowly increasing and in the last 2-3 years registered 

was the smaller number of incident cases while the cumulative morbidity is low (much 

lower compared with the European developed countries and Belgrade population-capital 

of Serbia). Among the HIV positive persons, AIDS was diagnosed most often after few 

months (up to 3 years after) and the survival time was on the average 1 year. 

Conclusions 

Throughout the World in Serbia and Montenegro and in Region of Nis the epidemiological 

situation regarding Morbus HIV is unfavourable on account of the increase of the 

proportion of heterosexually infected and the larger female proportion in the total number 

of the diseased and HIV positive individuals. 


PP 1.7 

Genetic Differences in the HIV-1 C2-V3-C3 Region Between Haiti and USA Isolates 

Indicate Differences in Adaptation at the Population Level 

Beatriz Perez-Sweeney 1 , Rob DeSalle 2 , John L. Ho 1 

1 

Division of International Medicine and Infectious Diseases, Weill Medical College of 

Cornell University, New York, NY 10021 

2 

Department of Invertebrate Zoology, American Museum of Natural History, New York, NY 

10024 

Haiti has the highest prevalence of human immunodeficiency virus type-1 (HIV-1) 

infection in the Americas. The first cases of acquired immunodeficiency syndrome (AIDS) 

in Haiti and the USA were documented in 1979. At this time the modes of transmission in 

these two settings and the racial/ethnic groups affected were different. Although HIV-1 

isolates from Haiti and the USA are presumed to be similar, formal genetic analysis has 

not been reported. A comparative study was conducted of the C2-V3-C3 region of the HIV 

envelope between Haiti and USA isolates, collected before 1994 and prior to the 

anti-retroviral era, and included 1) phylogenetic and population genetic analyses to 

determine HIV-1 divergence, 2) phylogenetic, population genetic and codon analyses to 

detect adaptive divergence indicative of selection, and 3) amino acid mapping to 

N-glycosylation motif and human leukocyte antigen (HLA) class I epitopes. Our data 

suggest that Haiti and USA HIV populations 1) show significant population genetic 

divergence even though they are both members of clade B and 2) exhibit selection 

pressures that account for the observed codon divergence localized in HLA binding 

epitopes, N-glycosylation motifs or both. We speculate that the selection pressure of host 

immunity leads to viral adaptation and HIV-variants capable of evading the immune 

system. Our data may be the first to detect adaptive divergence of HIV-1 isolates from the 

same viral clade. Comparing HIV-1 obtained from humans with different racial/ethnic 

backgrounds may uncover codon changes to guide vaccine design. 

POSTERS 


PP 1.8 

HIV transmission in The Gambia and the West African region 

A Akinsipe 1.2.3 , A Akinsipe 1 , P Akinsipe 1 

1 

Peoples Alliance to Combat HIV/AIDS,Banjul, The Gambia 

2 

African Microbicides Advocacy Group,Cape Town, South Africa 

3 

Gambia Microbicides Advocacy Group, KSMD, FAJARA, THE GAMBIA. 

Aims 

Mother -to-child transmission, people living with HIV/AIDS (PLWHA), counseling. 

Methods 

PPTCT programs in The Gambia are being scaled up. The extent of coverage is still 

Insufficient and the quality need to be further improved. 

Results 

As a counselor in a government PPTCT program I have identified the following key Issues. 

Many doctors are still hesitant to conduct vaginal deliveries for HIV positive women and 

Sometimes ask them to go to other hospitals for some unknown reasons. Most professional 

Counselors do not give adequate information on antiretroviral and options for 

Continuation/termination of pregnancy or breastfeeding. HIV positive mothers do not know 

much About nevirapine resistance and how it might affect their future 

treatment options. In rural areas Information about PPTCT programs is not widely 

available & also facilities are not available to Conduct deliveries in the primary health 

centers. 

Conclusions 

There is a need to intensively sensitize doctors/counselors to provide adequate 

Information to HIV positive mothers. Appropriate materials & adequate infrastructure are 

needed For conducting safer deliveries in urban & rural areas. Antiretroviral treatment 

needs to be offered To HIV positive mothers who satisfy the medical criteria. Increase the 

involvement of women living with HIV in the PPTCT service delivery. 


PP 1.9 

HIV/ HCV Transmission from HIV/HCV Co-infected Mothers to Infants 

I.A. Simonova, A.I. Mazus, E.V. Volochkova, J.F. Vladskaya, V.N. Khlamova, 

A.Ya. Olshanskiy, Yu.V. Martinov 

Moscow Centre for HIV/AIDS Prevention and Treatment, Moscow, Russia; Moscow State 

University of Medicine and Dentistry, Moscow, Russia 

We followed 80 infants born to HIV/HCV co-infected mothers for 5 years from the moment 

of birth. We detected HIV/HCV markers in blood samples: 1) HIV antibodies by ELISA and 

Western blot, 2) antibodies to core, NS3, NS4, NS5 antigens HCV by ELISA 3) HIV RNA, 

HCV RNA by PCR. 

Children were divided into 4 groups according to the test results. 

In the first group anti-HCV and anti-HIV disappeared in 44 infants (55%). In this group 

antibodies disappeared in 1 child by 3 months of age; 5 children by 6 months of age; 

5 children by 9 months of age; 12 children by 1 year of age; 10 children by 1 year and 6 

months of age; 8 children by 2 years of age; 2 children by 2 years and 6 months of age; 

and 1 child by 3 years of age. HIV antibodies started disappearing by 1 year of age in 6 

children; 1 year and 6 months of age in 13 children; 2 years of age in 18 children; 2 years 

and 6 months of age in 4 children; 3 years of age in 2 children; 4 year and 9 months of 

age in 1 child. Children in this group were diagnosed as free from HIV/HCV when 

testing negative for HIV RNA, HCV RNA. Thus, no HIV/HCV transmission from mother to 

infant was detected in this group. 

In the second group anti-HIV disappeared completely in 11 children (13.7%) by 3 years of 

age, while they remained anti-HCV-positive. PCR revealed HCV RNA in all the children, 

which confirmed HCV transmission from mother to child. 

In the third group on the contrary, anti-HCV disappeared completely in 11 children (13.7%) 

by 3 years of age, while they remained anti-HIV-positive. PCR revealed HIV RNA in all the 

children, which confirmed HIV transmission from mother to child. 

In the fourth group 14 children (17.5%) were diagnosed with HIV/HCV co-infection at the 

age of 5. They tested positive for anti-HIV and anti-HCV and PCR revealed HIV RNA and 

HCV RNA in all the children. 

We detected earlier elimination of HCV antibodies than HIV antibodies in children born to 

HIV/HCV co-infected mothers and possible transmission of HIV and HCV from mother to 

infant. 

POSTERS 


PP 1.10 

Evaluation of Prevalence and Risk of HBV, HCV and HIV Infections in Health Care 

Workers 

Gratiana Chicin Dana Brehar Cioflec 

Institute of Public Health Timisoara Romania 

Objectives 

The study aimed at assessing the prevalence of accidents with exposure to blood and 

other biological products in health care workers(HCW), detecting risk factors for HBV, 

HCV and HIV infection, and detecting HBV, HCV and HIV infections in HCW. We also tried 

to identify measures for surveillance and control of accidents with exposure to blood and 

other biological products and to design proposals and preventive measures in order to 

decrease morbidity by these infections. 


The study included 417 subjects in whom we tested for serum markers of: HBV(HBsAg 

and HBsAb), HCV(HCVAb), HIV(HIVAg/Ab) by enzyme immunoassay. All subjects were 

interviewed based upon a specially designed questionnaire with data on blood exposure 

accidents in different health care departments. We used the method of descriptive 

epidemiological analysis and odds ratio(OR) for risk analysis. 

Results 

Out of 417 subjects, 50% declared at least one accidental blood exposure(ABE) during 

the previous 3 months. The prevalence of accidents was 38% in physicians, 57% in 

graduate nurses, 52% in undergraduate nurse, 17% in other cathegories of HCW. The 

distribution in various medical specialities showed an occurence of ABE of 46% in 

non-surgical and 63% in surgical departments. The prevalence of HBV and HCV 

infections was 3,8% and 1,7%, respectively.We detected a prevalence of 26,3% subjects 

with protective anri-HBV antibodies; questionnaire analysis showed 36,5% completly 

vaccinated subjects(3 anti-HBV vaccine doses), 48,4% nonvaccinated subjects, 4% with 

unknown and 11% with unspecified vaccinal status. None of the 417 subjects tested 

positive for HIV Ag/Ab. The analysis of various associations showed an OR of 1,84 

between ABE by puncture and HBs Ag positivity. The other analysed associations showed 

nonsignificant OR values. 

Conclusions 

Most exposed HCW proved to be graduate and undergraduate nurses and members of 

the auxilliary staff. Most frequent accidents occured by splashing of blood on injured skin 

or mucous membranes, followed by punctures with contaminated needles. 

There is a need for educational programmes for nurses and auxilliary staff membres, 

implementation of vaccination programmes and evaluation of high risk procedures and 

devices. 

Altough none of the subjects tested positive for HIV Ag/Ab, the risk of infection is present 

given the high prevalence of ABE in HCW. 


PP 1.11 

HIV/STD Prevention need assessment among sex workers in Nepal 

Birendra Poudel 

Programme Officer, CAADa Nepal, Kathmandu, Nepal 

Sexual services that do not involve vaginal intercourse has started to emerge in capital 

city of Nepal. Though this kind of non-vaginal sector of sex industry is illegal, they are still 

virtually semi-underground condition and HIV/STD prevention intervention for sex 

industry has not activated insufficient. we focused on the female-sex workers working in 

non -vaginal sector in Katmandu to know their needs for HIV/STD prevention to develop 

efficient program for them. 

Methods 

We conducted questionnaire research for sex workers to ask their attitudes and needs on 

STD/HIV prevention. Questionnaire was distributed for 250 workers were responded. 

Results 

Half of respondents answered they think the possibility of STD infection their service is 

high or very high (42.4%). Many of respondents need information abut STD, such as how 

to prevent STDs (65.o%), symptom and treatment of STD (52.7%). Most of respondents 

work only non-vaginal and they feel easy to obtain the information by magazine (53.5%) 

and internet (43.9%)/ on the workplace (65.7%)or clinics (47.3%). 

Conclusions: 

the results suggest that the information should be specialized for non-vaginal sector such 

as STD prevention methods for oral sex. It is also suggested that to provide information 

on the workplace through internet are useful for sex workers. 

POSTERS 


PP 1.12 

Co-morbidity of HIV, Hepatitis B, and Syphilis, among victims of sexual assaults in 

Transkei region, South Africa 

Banwari MEEL 

Walter Sisulu University, Mthatha 5117 South Africa 

Background 

HIV/AIDS, hepatitis B, and syphilis have a common mode of transmission through sexual 

intercourse. These are also transmitted percutaneously and by blood transfusions. The 

purpose of this study is to determine the prevalence of HIV, hepatitis B, and syphilis 

among victims of sexual assaults, by analysing serology results. 

Method 

This is a record review of victims of sexual assault who attended the Sinawe Centre 

(clinic for victims of sexual assault), between January and December 2004. 

Results 

One hundred and eighty eight victims of sexual assault were reported, of whom 35(19.8%) 

tested HIV seropositive. Hepatitis B antibodies were detected in 7(7.6%), and RPR was 

positive in 5(2.9%). Except 1 victim, all the rest were under 50 years of age. Out of the 35 

who tested positive, 30 were below 30 years of age. Of those who were 30 years and 

younger, 12 were between 21 and 30 years, 16 between 11 and 20 years and 2 were less 

than 10 years. None was positive for all three tests. Two were positive for hepatitis B and 

HIV, and 2 others were positive for RPR and HIV. 

Conclusion 

There is no significant co-morbidity of HIV, hepatitis B and syphilis observed in this study 

although they have the same mode of transmission. 


PP 1.13 

Prevalence of HIV in Mthatha area of South Africa, as estimated from testing of rape 

victims 

BANWARI MEEL, MD. 

Walter Sisulu University, Mthatha, P/Bag X1 Unitra, Mthatha 5117, South Africa. Tel: 047 

502 2963, Fax: 047-502 2107 E-mail: meel@getafix.utr.ac.za 

Background 

There are tremendous challenges remaining in the field of HIV education, prevention and 

care in South Africa. There are conflicting reports on the prevalence of HIV from two studies. 

Antenatal surveillance (DOH, 2004) showed 29.5% prevalence whereas National 

HIV survey (National Survey 2005) showed only 10.8%. There is a need of a third estimate 

in such a situation. 

Objective 

To estimate HIV prevalence and incidence in Mthatha area of South Africa. 

Methods 

Retrospective review of HIV testing results among victims of sexual assault who 

presented first time to the Sinawe Referral Centre, Mthatha General Hospital, for the 

period 2001 - 2005 (inclusive). 

Results 

Between 2001 and 2005, 1691 victims of sexual assault presented to Sinawe Referral 

Centre. Of these 1435 (84.8%) were tested for HIV at the time of first consultation. One 

hundred and ninety seven (13.7%) were found HIV seropositive on the screening test. In 

a space of 3 years (2001 - 2004), there was an increase in the prevalence of HIV 

positivity from 0.9% to 6.4%. There was also an increase in the young age groups 

between 16 and 25 years. The highest HIV prevalence (26.9%) was found in age group 

of 16 to 20 years. 

POSTERS 

Conclusion 

There is high prevalence of HIV infection, and just over a half (50.8%) of HIV positive rape 

survivors were aged 16 - 25 years. 


PP 1.14 

Screening for HIV-infection and mother-to-child transmission of HIV among 

pregnant women attending a maternity ward in Dakar (Senegal) 

Birahim Pierre Ndiaye (1), Alassane Diouf ( 1 ), and Moussa Sarr ( 2 ) 

1 

Hopital Aristide Le dantec, Dakar, Senegal 

2 

Westat, Inc., Rockville, MD, 20850, USA 

Objectives 

The objective of the study is to determine the prevalence of HIV infection in pregnant 

women in Dakar and their infants in Dakar. 

Methods 

Systematic screening was performed among pregnant women admitted to the University 

Hospital maternity ward for delivery. Women who were positive were confirmed by 

Western Blot. Children of HIV positive mothers were tested using RNA-PCR essays. 

In addition to the HIV positive women identified through regular screening, other HIV 

positive women were also referred to the maternity ward for delivery from HIV and 

Infectious disease clinics in the area. 

Results 

From June 2000 to June 2004, 874 were proposed to screen for HIV infection, and 691 

tests were performed (79.06%) among women who consented for the testing. Twenty four 

women tested HIV positive out of 691, for a prevalence of 4% 95% CI (0.6% - 7.4%). 

During the same period, an additional 102 HIV infected women were referred to the 

department for delivery, in addition to the 24 HIV infected women identified during the 

regular screening procedures. Overall, 5 HIV positive children were born from a total of 

126 HIV infected mothers. The overall transmission rate was 4.00% 95%CI (0.6% - 7.4%). 

A total of 66 HIV positive women who attended the clinic prior to delivery for prenatal care 

received short-term antiretroviral therapy, and 16 c-section were performed. 

A significantly lower transmission rate of 1.5% (0 - 3%) was found among women who 

received a short-term ARV prophylaxis at delivery +/- C-section. 

Conclusion 

These results show an HIV prevalence rate higher than the national average turning 

around 1%. This may be related to a self-selection of women at risk for HIV infection 

knowing that support can be obtained in the department. Other socio-demographic 

characteristics could also explain this high prevalence and should be investigated. 

HIV transmission rates from the mother to the child can be considered as low, mainly 

among those who received short-term ARV +/- C-section. 


PP 1.15 

HIV genotoyping on filter paper (DPS): a new method for HIV resistance 

epidemiological survey 

PLANTIER JC, DACHRAOUI R, TRABELSI A, SIMON F. 

Laboratoire de virologie CHU de ROUEN- FRANCE Faculte de Médecine-Pharmacie de 

SOUSSE, TUNISIE 

Objective 

to genotype the HIV-1 strains collected on dried plasma spots (DPS), deposited in Tunisia 

(North Africa) and sent by mail in France. 

Methods 

20 µL of plasma samples from 35 HIV-1-infected Tunisian patients, with viral load values 

ranging from 2.25 Log (177 copies/ml ) to > 5.9 Log (750 000 copies/ml), were deposited 

on filter paper (DPS) in Tunisia. DPS were conserved in a plastic bag with a desiccant, at 

room temperature and +4° and mailed to France. The delay between collect and sending 

was 5-10 days. Matched plasma were processed for plasma viral load (PVL, Cobas 

Monitor Roche). At reception, DPS were conserved at -80°C until experiments. After 

elution and RNA extraction, nested RT-PCR was used to amplify the protease, RT regions 

of the pol gene and the gp41 region of the env gene (enfuvirtide target). Resistance 

sequencing was performed on all the protease and RT and gp41amplicons. 

The sequences obtained were analysed for resistance mutations and phylogenetic 

positions 

Results 

Protease region was successfully sequenced in 27/35 (77.1%), RT in 25/35 cases (71.4%) 

and gp41 in 21/31 cases (67.7%). Standard controls on matched plasma samples were 

negative in four samples. All samples with PVL > 4 Log (n=27) were 

successfully amplified in the Protease (100%) and 25 (92.6%) in the RT ; 21 of the 24 

samples were positive with our gp41 protocol (87.5%). Three out of the 8 samples with 

PVL < 3.7 Log were successfully amplified in the Protease region and one in the gp41 

region. Sequencing showed mutation profiles in accordance with the treatment status. 

Phylogenetic analysis concluded to HIV-1 subtype B in all the samples in the different 

sequenced regions. 

POSTERS 

Conclusion 

Our results obtained in field conditions confirm that monitoring resistance survey can be 

performed in developing countries. Optimisation to improve sensitivity for viral load below 

4 Log is in progress. DPS is simple and easy to transport (by mail) and is a potential tool 

for individual and epidemiological monitoring throughout the world. 


PP 1.16 

Low performance of HIV-1 serotyping in high HIV epidemic geographical areas 

L. Tavoschi ( 1 ), D. Bernasconi ( 1 ), M. Chiappi ( 1 ), C. Galli ( 3 ), B. Suligoi ( 2 ), E. Salvi ( 1 ), 

Cissy Kityo ( 4 ), B. Ensoli ( 1 ) and S. Buttò ( 1 ) 

1 

National AIDS Center, Istituto Superiore di Sanità, Rome, Italy; 

2 

Dipartment of Infectious, Parasitic and Immuno Mediated Diseases, Parassitarie e 

Immunomediate, Istituto Superiore di Sanità, Rome, Italy; 

3 

Abbott Diagnostic Division, Rome, Italy; 

4 

Joint Clinical Research Center, Kampala, Uganda 

Objectives 

Investigation on HIV subtypes distribution is essential for the knowledge of the epidemic 

spread. In developing countries and, in particular, in sub-Saharan Africa, which is the 

hardest-hit region, the extreme HIV heterogeneity is a major obstacle for both the evaluation 

of the impact of antiretroviral therapies and the development of an effective vaccine against 

HIV/AIDS. Since serotyping has been proposed as a rapid, simple and inexpensive method 

for the study of the geographical distribution of various HIV-1 strains, we investigated the 

performance of this assay in Uganda, a geographical area with high HIV epidemic. 

Methods 

We examined 148 repository HIV positive serum samples from 118 Ugandan individuals. 

For all the 118 participants the date of seroconversion was estimated as the midpoint 

between the last negative and the first positive HIV test; the interval between the two tests 

was

PP 1.17 

In the Footsteps of the WHO - Rapid HIV Testing in America 

Eugene Martin, Ph.D. 1 , Gratian Salaru, M.D. 1 , Sindy M. Paul, M.D., M.P.H. 2 , 

Evan Cadoff, M.D. 1 

1 

UMDNJ - Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA 

2 

New Jersey Department of Health and Senior Services, Trenton, New Jersey 

Background: In the United States, only 4 rapid HIV tests have received FDA approval. In 

excess of 60 rapid HIV tests are in use worldwide. In some resource-poor countries, 

confirmatory testing by alternative rapid assays is also in widespread use. In the United 

States, rapid HIV testing allows preliminary positive results to be recognized in minutes, 

but still requires traditional confirmation by complex, time-consuming methodologies. In 

some cases, the reported sensitivity and specificity of rapid tests equals or exceeds that 

of conventional enzyme immunoassays (EIA) as well as the confirmatory Western blot 

and/or IFA tests they were intended to confirm. This results in large numbers of negative 

or indeterminate confirmatory tests that require significant efforts to clarify. 

In densely populated states such as New Jersey, efforts to control the spread of HIV relies 

upon rapid HIV testing in a multitude of venues including outreach centers, satellite 

facilities, hospital ERs, methadone clinics, perinatal clinics, and increasingly, mobile units. 

Unfortunately, as many as 30% of preliminary positive HIV clients fail to receive final 

results because of their unwillingness to return for a second visit and the goal of HIV 

awareness remains hostage to an aging confirmatory methodology. 

Objectives:To provide an update of rapid HIV testing in the United States, particularly in 

New Jersey with an emphasis on the consequences of Western blot confirmation. An 

alternative method of confirming a rapid HIV test with a second, alternate rapid HIV test 

has been utilized retrospectively to assess the feasibility of confirming a rapid HIV result 

with a secondary rapid HIV test. 

Methods: Between July 1, 2004 and Feb 28, 2005 13,500 rapid HIV tests were 

performed in New Jersey CTS locations identifying a total of 250 preliminary positive 

individuals. Traditional confirmatory testing by Western Blot identified 9 cases as 

discordant (.067%) i.e. a preliminary positive rapid test and a negative Western Blot. 

Utilizing residual serum samples available in the public health laboratory repository, 

alternative rapid HIV tests were performed using 3 other tests approved for use in the 

United States including: Multispot HIV-1/HIV-2 Rapid Test (Bio-Rad Laboratories, 

Redmond, WA 98052), MedMira Reveal Rapid HIV-1 Antibody Test (MedMira 

Laboratories, Inc, Halifax, Nova Scotia, Canada B3S 1B3), Uni-Gold (Trinity Biotech plc, 

Wicklow, Ireland). 

POSTERS 

Results: Two of three alternative rapid tests (Trinity Uni-Gold (CLIA-waived) and MedMira 

Reveal (moderate-complexity, non-CLIA-Waived) successfully identified all nine 

discordant specimens as non-reactive. Of 355 Western blot confirmed rapid HIV 

specimens collected between July 1, 2004 and April 19, 2005, 100% concordance was 

obtained using all three available alternative rapid assays. 

Conclusions: Rapid HIV testing has become a major means of increasing awareness of 

HIV serostatus in the United States. Annually, use of a confirming rapid test algorithm in 

New Jersey would allow an additional 91 HIV positive individuals to learn their definitive 

status and would assure a better linkage to health care for affected individuals. 


PP 1.18 

The spread of HIV-1 resistance mutations in the South of Russia 

Shemshura A.B., Svechnikova L.V., Poddubskaya S.Y., Fomina N.G., Saukhat S.R. 

Rostov Southern AIDS center, Rostov-on-Don, Russia 

The aim of the study was the examination of drug-resistant HIV-1 strains in the South of 

Russia. There was carried out sequencing of HIV-1 pol gene part coding of the revertase 

in viral RNA samples in 22 HIV-infected patients (treated with HAART and untreated) from 

the South Federal District of Russia. 

Primary and secondary resistance mutations for NRTI and NNRTI were absent in 

untreated patients in comparison with the other group of patients. 

The treated patients showed differences in mutations in HIV-1 pol gene depending on the 

degree of viral replication inhibition. It was found, that in successfully treated patients 

?70R, M184V and K219Q mutations were registered more often, while in the patients with 

the viral rebound - T215Y/F and L74V were registered more often. Together with this, the 

lower CD4 count in the group of patients with unsuccessful viral replication inhibition was 

marked. 

Thus, our results testify that accumulation of resistance mutations in the HIV-1 pol gene 

positions 215, 74, 103, 181, 41 as well as their combinations during HAART further the 

efficiency decrease of NRTI and NNRTI included in HAART combination. To confirm this, 

more extensive investigations should be taken. 


PP 1.19 

Knowledge and Practice in Post-exposure HIV Prevention for Medical Staff in 

Moscow 

A.I Mazus, G.Yu. Pankova, A.A. Goliusov, Yu.V. Martynov 

Moscow Centre for HIV/AIDS Prevention and Treatment, Moscow, Russia; Moscow State 

University of Medicine and Dentistry, Moscow, Russia 

Today the HIV epidemiological situation in the Russian Federation and Moscow is 

complicated. The HIV prevalence in Moscow was 236.8 per 100,000 population in 2005 

(with the annual increase of 23.34 per 100 000 population). The HIV epidemiological 

survey has shown that HIV testing (together with pretest and post-test counseling) is 

made for patients entering the surgery and obstetrics hospitals. The patient's HIV status 

is defined in the first 48 hours after his/her admittance. This makes it possible in case of 

the medic's exposure to biological agents to provide them with post-exposure HIV 

prophylaxis in 48 hours after the contact. 

Questionnaires were used to assess the medical staff behavioral factor after HIV 

exposure. 

In Moscow 2,145,231 patients were tested for HIV in 2003 and the number increased by 

7.1% in 2005. The number of HIV-infected patients in the Moscow hospitals increased by 

38.1% in the same year. The relative HIV risk factor increased RR=1.4-fold in 2005 

compared to 2003. 

Of the medical staff exposed to the risk of HIV infection at work just 47.2% addressed for 

urgent medical aid in the first 48 hours after exposure. The high level of the possible risk 

of infection was detected in 11.1% of all cases, the average level - in 56.5% and minimal 

- in 32.4%. Among dentists 36.6% reported accidents at work in the past 6 months, with 

the median number of 1.24 accidents during the workday. The correct behavioral 

algorithm in such situation was known just to 1/3 of the respondents. 

The retrospective and effective epidemiological analysis resulting from the epidemiological 

survey, has shown that the behavioral algorithm in case of occupational exposure to HIV 

must be learned and trained. 

POSTERS 


PP 1.20 

Study of the anti-HIV recombinant vaccinia viruses 

Babkin I.V., Babkina I.N., Nesterov A.E., Ryazankin I.A., Danilyuk N.K., Seregin S.V., 

Belavin P.A., Bazhan S.I., Shchelkunov S.N. 

State Research Center of Virology and Biotechnology "Vector", Koltsovo, Novosibirsk 

region, Russia 

The goal of this project is to design anti-HIV vaccines involving recombinant vaccinia 

viruses and to research vaccines immunogenicity. Two recombinant vaccinia virusescandidate 

anti-HIV vaccines-were produced by homologous recombination between the 

earlier constructed integration plasmids and vaccinia virus (strain Lister variant LIVP) at 

TK-flanking segments of thymidine kinas gene. The recombinant viruses were created: 

VV-TCI, VV-TCI-HBsAg. Earlier the artificial T cellular immunogen TCI containing about 80 

CTL epitopes selected from the database on HIV molecular immunology was constructed. 

The genetic constructs expressing the artificial TCI protein and TCI protein fused to the 

HBsAg were obtained. The immunogenic properties of development recombinant viruses 

were studied after a single intracutaneous immunization of BALB/c mice at a dose of 

2 × 106 PFU per animal. The recombinant viruses studied induce both cell-mediated and 

humoral immunity to HIV proteins. Immunization of mice by VV-TCI resulted in a more 

pronounced humoral immune response. The results of CTL study demonstrated that a 

statistically significant increase in the activity of cytotoxic T lymphocytes in response to 

stimulation occurred on day 7 post immunization of mice and remained until the end of 

experiment. The maximal statistically significant activation of spleenocytes from the 

animals immunized with VV-TCI and VV-TCI-HbsAg by recombinant HIV proteins 

occurred on day 21 post vaccination. The data obtained show that recombinant virus 

VV-TCI may be considered as the best candidate vaccine against human 

immunodeficiency virus. 


PP 1.21 

A candidate oral vaccines against hepatitis B virus and human immunodeficiency 

virus based on transgenic tomato and carrot plants 

Sergei N. Shchelkunov, Rurik K. Salyaev, Natalia I. Rekoslavskaya, Sergei G. 

Pozdnyakov, Andrei E. Nesterov, Elena V. Deineko, Vladimir K. Shumnyi, Galina A. 

Shchelkunova, Rosemarie W. Hammond 


region, 630559 Russia; Institute of Chemical Biology and Fundamental Medicine, Siberian 

Branch of the Russian Academy of Sciences, Novosibirsk, 630090 Russia; Institute of 

Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 

Novosibirsk, 630090 Russia; Siberian Institute of Plant Physiology and Biochemistry, 

Siberian Branch of the Russian Academy of Sciences, Irkutsk, 664033 Russia; Molecular 

Plant Pathology Laboratory, United States Department of Agriculture, Agricultural 

Research Service, Beltsville, Maryland, USA 

Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) cause very dangerous 

diseases in humans, with combined morbidity rates exceeding 1-3 million people 

annually. Vaccination is the most efficient method for protection against viral diseases. 

Therefore, there is a need for large quantities of safe, efficacious, easily administered, and 

low cost vaccines. A synthetic chimeric gene, TBI-HBS, encoding the immunogenic ENV 

and GAG epitopes of HIV-1 and the surface protein antigen (HBsAg) of HBV, was 

introduced into tomato and carrot plants using the agrobacterial vector plasmid. Fruits of 

transgenic tomato expressing the TBI-HBS antigen were fed to experimental mice and, on 

days 14 and 28 post-feeding, high levels of HIV- and HBV-specific antibodies were found 

in the serum and feces of test animals. Intraperitoneal injection of a DNA vaccine 

directing synthesis of the same TBI-HBsAg protein boosted the antibody response to HIV 

in the blood serum; however, had it no effect on the high level of antibodies produced to 

HBV. In summary, it was found that the levels of HBsAg and TBI antigens in transgenic 

tomato fruits were able to induce the formation of an immunogenic response in mice after 

oral delivery of the vaccine. 

The work was supported by International Science and Technology Center (grant No. 

2176p). 

POSTERS 


PP 1.22 

Comparative investigation of the DNA-Vaccines against HIV based on artificial gene 

TBI 

Babkina I.N., Babkin I.V Nesterov A.E, Shchelkunov S.N. 


region, Russia 

The first goal of this project is to design anti-HIV DNA vaccines and the second goal is to 

research DNA-vaccines immunogenicity. Genetic engineering techniques were used to 

construct three variants of expression plasmids with artificial gene coding protein TBI. The 

protein TBI, comprising four a-helices connected with hydrophilic loop segments, was 

proposed as a potential immunogen mimicking HIV-1. The a-helix regions contain T-cell 

epitopes for T-helper and cytotoxic T-cell lymphocytes. The loop regions contain five 

neutralizing B-cell epitopes. Three genetic constructs expressing the following 

recombinant proteins were obtained: the recombinant protein TBI, TBI fused to the signal 

peptide of human ß2-microglobulin and TBI fused to the signal peptide of human 

ß2-microglobulin and transmembrane domain of HIV-1 Env protein. The variants of TBI 

gene, encoding four T cell epitopes and five B cell epitopes, were inserted into the 

plasmid pcDNA3.1-mycchislacZ(-). This plasmid comprises promoter of cytomegalovirus, 

recognized by eukaryotic RNA polymerase, and polyadenylation signal, allowing for an 

efficient expression of the target gene in eukaryotic cells. DNA vaccines were obtained in 

the complex of plasmid DNA with the protective cover virus-like particles (VLP) for 

increasing their immunogenicity and development of the delivery systems. VLP-DNA 

contained plasmid with cover composed of polyglucin-spermidine. 

Plasmid DNAs and VLP-DNA were used to immunize model animals (BALB/c mice). The 

comparison of immunogenicity of the plasmids in question was carried out. Nonspecific 

reactions of experimental animals to vaccination were also studied. Humoral immunity 

characteristics were assessed by EIA of peripheral blood sera of model animals. It was 

demonstrated that the immunization with pcDNATBI plasmid induced the highest level of 

antibodies to HIV. The genetic constructs studied induce the cell-mediated immune 

response to HIV proteins. Investigation of the immune response using CTL test 

demonstrated that the maximal activity of cytotoxic T lymphocytes in response to their 

stimulation with HIV recombinant proteins appeared when using pcDNATBI plasmid. 

Assay of the cell-mediated immune response by blast-transformation reaction showed 

that the maximal activation of spleenocytes by HIV recombinant proteins occurred in the 

case of the plasmid pcDNASTBID. The data obtained show that pcDNATBI plasmid may 

be considered as the best candidate vaccine against HIV. 


PP 1.23 

Impact of a School-based HIV/AIDS Educational Intervention on Students' 

Behaviour Intentions in Ukraine 

Pavlo Kyrychenko*, MD, PhD 

Nalini Sathiakumar**, MD, DrPH 

Tetyana Kyrylyuk***, MD, MSc 

*Department of Infectious Diseases and Epidemiology, Vinnitsa National Pirogov Memorial Medical University, 

Vinnitsa, Ukraine 

**Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA 

***Vinnitsa Regional AIDS Centre, Ukraine 

Objectives: Ukraine has rapidly become one of the world's fastest growing regions for the 

spread of HIV infection and Ukrainian youth can be counted as a high-risk group for the 

disease. Our study assessed changes observed in senior students' behaviour intentions 

following a secondary school-based HIV/AIDS educational intervention in Vinnitsa, 

Ukraine. A thorough review of the scientific literature did not reveal any studies corresponding 

to this issue in the country. 

Methods: The study was conducted among 15-16 year old school students in 2004 using 

a quasi-experimental, non-equivalent control group design with pre-test - post-test 

components. Among 40 government secondary schools of Vinnitsa city we randomly 

selected two. One received HIV/AIDS intervention and the other served as a control. In 

total 200 randomly selected students (100 from the each school) were involved into the 

study. Outcome behaviour variables were measured by proportions and Pearson 

chi-square test was applied to assess their changes after intervention and in a 

three-month follow-up period. Finally, logistic regression analysis was employed to 

evaluate associations between level of knowledge and behaviour intentions. 

Results: At baseline intervention and control schools had no statistically significant 

differences on students' socio-demographic characteristics, HIV knowledge and behaviour 

intentions, and we reported no knowledge and behaviour changes in the control group at 

the first and second post-tests. At the same time, our educational programme contributed 

to a significant improvement in mean HIV knowledge scores for students in the 

intervention group (from baseline 83.2 ± 6.4 (Standard Deviation) to post-test 96.2 ± 6.2, 

p

PP 1.24 

Foreign Citizens Admitted to the general teachning Hospital of Bologna, 

North-Eastern Italy. An Epidemiological and Clinical Survey 

Roberto Manfredi 1 , Elena Baldi 2 , Sergio Sabbatani 1 

1 


2 

Dept. of Hygiene and Public Health, University of Bologna, Italy 

Introduction. The emergency regarding recent immigration waves towards Italy makes 

necessary a continued health care monitoring of these patient populations. Methods. 

Based on a database-guided survey of hospital admissions carried out during the last five 

years at the S. Orsola-Malpighi General Hospital of Bologna (Italy), all causes of admission 

of these subjects were evaluated, together with several their correlates. Subsequently, we 

focused on admissions due to infectious diseases. All available data regarding foreign 

citizens admitted as inpatients or in Day-Hospital settings of our teaching Hospital from 

January 1, 1999, to March 31, 2004, were assessed. Diagnosis-related group (DRG) 

features, and single discharge diagnoses, were parallelely evaluated, and a further 

assessment of infectious diseases was subsequently made. Results. When examining a 

comprehensive pool of 339.051 hospitalized patients, foreign citizens discharges were 

7,312 (2.15%), and regarded 2,542 males (34.8%) and 4,769 females (65.2%). Males had 

a mean age of 36.8±14.7 years, while females were aged 30.8±12.2 years. When 

assessing the areas of origin, 34.6% of hospitalizations was attributed to patients coming 

from Eastern Europe, 15.3% from Northern Africa, 7.3% (comprehensively) from Western 

Europe and United States, 6.9% from Indian subcontinent, 5.9% from subsaharan Africa, 

5.7% from latin America, 4.1% from China, 2.5% from Philippines, and l'1.1% from Middle 

East. Among women, the great majority of hospitalizations (58.8%) was due to obstetricalgynecological 

procedures or diseases, including assistance to delivery (27.1%), and 

pregnancy complications (18.7%), followed by psycho-social disturbances (5.9%), 

malignancies (5.1%), gastrointestinal diseases (4.7%), and voluntary pregnancy 

interruption (4.4%). Among men, the most frequent causes of admissions were related to 

trauma (15.9%), followed by gastroenteric disorders (12%), heart-vascular diseases 

(8.9%), psycho-social disorders (8.4%), respiratory (7.1%), kidney (6.1%), liver (5.2%), 

and metabolic (4.9%) diseases, and alcohol or substance abuse (4.2%). Infectious 

diseases (alone or with concurrent disorders) were reported in 881 discharged individuals, 

representing 12.1% of the 7,312 DRGs attributed to foreign patients. The comprehensive 

patient population discharged from our Hospital with at least one infectious disease 

diagnosis had lower respiratory tract infections, followed by chronic viral hepatitis, HIV 

infection and related diseases, enterocolitis, pulmonary tuberculosis, pyelonephritis, 

severe skin and soft tissue infection, meningoencephalitis, and malaria, as the most 

frequent reported disorders. Conclusions. Our survey, through a combined analysis of 

both DRGs and discharge diagnoses, allowed us to identify that 12.1% of foreign citizens 

hospitalized at our General teaching Hospital of Bologna (Italy) suffered from at least one 

infectious disease. Respiratory tract, liver, and gastrointestinal infections, and HIV 

disease, were quoted with an appreciable frequency among discharge diagnoses, while 

the frequency of malaria and meningoencephalitis seemed lower, compared with other 

series. Among disorders other than infectious ones, obstetric-gynecological conditions 

and post-traumatic episodes (for male patients), represented the most frequent causes of 

hospitalization. 


PP 1.25 

Risk factors for human herpesvirus 8 (KSHV/HHV-8) viremia in AIDS patients with 

Kaposi's sarcoma 

Ligia Camera Pierrotti( 1 ); Laura Masami Sumita (2); Wilton Santos Freire ( 2 ); 

Vanda Akico Ueda( 2 ) Fick de Souza 

1 

Clinical Hospital and 2 Virology Laboratory; University of Sao Paulo, Sao Paulo, Brazil 

There are several epidemiological, virological and serological lines of evidence 

suggesting that human herpesvírus 8 (HHV-8) is the cause of Kaposi's sarcoma (KS) and 

previous studies have provided evidence for a link between HHV-8 replication and KS 

pathogenesis. However few prospective studies investigating the relationship between 

HHV-8 replication and possible risk factors have been published. 

The present study intended to evaluate the HHV-8 replication and humoral host response 

to HHV-8 infection in a cohort of AIDS patients with KS assisted at AIDS Outpatient Clinic 

- Fundação Zerbini, and estimates the prevalence and the risk factors for HHV-8 viremia. 

The patients were follow-up periodically along the study for blood collection and clinical 

data information about HIV/AIDS evolution and KS evolution. Positive HHV-8 viremia was 

defined by the presence of HHV-8 DNA in peripheral blood mononuclear cells (PBMC) in 

at least one of two nested-PCR amplifying fragments of 170 bp. or 233 bp. HHV-8 

antibodies were detect by either indirect immunofluorescence assay (IFA) for lytic or 

latency-associated nuclear antigen (LANA) antigens or ELISA for lytic phase-ORF 65 

recombinant antigen. To analyze the effects of various factors on the risk of HHV-8 

viremia the generalized estimating equations models for cluster data were used. 

From March 1998 to July 2000 419 clinical and laboratorial evaluations of 42 AIDS patient 

with KS they were available. HHV-8 viremia was detected in 146 (35.6%) evaluations. 

seropositivity was higher for antibodies to lytic HHV-8 antigens than antibodies to latent 

HHV-8 antigens in the population studied (99.0%, 86.3% and 80.1% of seropositivity by 

IFA-LYTIC, ELISA-LYTIC and IFA-LANA, respectively). The seropositivity for antibodies to 

lytic HHV-8 antigens preceded the seropositivity for antibodies against the latent antigens. 

In the univariate analysis, the positive HHV-8 viremia was associated with KS clinical 

stage at the study admission (OR 1.93 for visceral KS, p=0.009) and opportunistic 

infection occurrence (OR 3.04, p=0.02) variables. In the multivariate analysis, the positive 

HHV-8 viremia was associated with category of exposure to HIV (OR 1.61 for 

homosexual; OR 3.64 for bisexual; p=0.03), KS clinical stage at the study admission (OR 

2.22 for visceral KS, p=0.01), and specific therapies against KS (OR 3.82 for expectation 

therapy, p=0.01) variables. There were no association between HHV-8 viremia and the 

others studied variables (sociodemographic informations, number of cutaneous KS 

lesions at the study admission, time from KS diagnosis to study admission, CD4+ 

lymphocyte T count, plasma HIV load, IP, ITRN and ITRNN use, SK clinical evolution, and 

titres of antibodies against HHV-8). 

The largest rate of the HHV-8 DNA detection in PBMC in patients with KS visceral in 

relationship those with non visceral KS support the use of HHV-8 viremia as a prognostic 

marker of the tumor in AIDS patients with KS. 

POSTERS 


PP 1.26 

Morbidity pattern of PLWA receiving emergency care at PEPFAR treatment centre, 

University College Hospital, Ibadan. 

Olowookere SA, Adetunji AA,Babalola TB,Aken'Ova YA,Adewole IF, Kanki P 

Harvard PEPFAR, Boston, USA. 

Background 

PLWA accessing care at University College Hospital until recently do so via various clinics 

(Accident and Emergency and General Outpatient Department/Medicine Outpatient) 

however with the establishment of the Day care at the PEPFAR treatment centre, very ill 

patients are now treated there. 

Method 

All patients attended to at the day care between June 2005 and January 31st 2006 were 

included in the study to determine reason for emergency care, care and treatment 

outcome. A detailed review of hospital case records was done. 

Results 

A total of 2585 PLWHA assessed care and treatment in the Unit during the year 2005. 

1300 were new patients. Of these PLWHA, 122 (4.7%) were attended to at the day care. 

There were 59 Males (48.4%) and 63 Females (51.6%). Mean age 37.16yrs (SD 8.129), 

modal age group 30-39 yrs. 33 (27%) were artisan, 26 (21.3%) were traders. 90 (73.8) 

presented with CD4 less than 200. 20(16.4%) had plasma viral load >100,000 /ml on 

presentation. 

Major reason for day care include diarhoea illness 55 (45.1%), chest infection 27 (22.1%), 

anaemia 18(14.8%) and febrile illness 11 (9%). 2 (1.6%) presented in coma. 50 (41%) 

were admitted into the Hospital while 72(59%) were discharged home after resuscitation 

and care in the day care room. No PLWA died at the daycare during the study period. 

Conclusion 

Establishment of the daycare at the PEPFAR treatment center had improve access to care 

for very ill patients and had improved survival of these patients. 


PP 1.27 

AIDS Prevention Program for MSM: Findings from a Baseline Survey in Lahore 

Pakistan 

Dr. Tanvir Ahmad Zaver 

Contech International Health Consultants 2-G Model Town Lahore Pakistan 

Lahore is second largest city of Pakistan and 45 th of the world with population of 8.5 

millions and estimated number of MSM is 180,000, high-risk group for HIV/AIDS. A World 

Bank funded project through Provincial AIDS Control Program, Government of the Punjab, 

was launched in April 2004 aimed to target MSM in Lahore. Main objectives of the project 

include behavior change and promotion of use of condom among MSM. Four Special 

Health Centers were established in the project area as a strategy to achieve the 

objectives. A Behavior Change Strategic Model was prepared. Specific activities in various 

stages transform unfelt need of MSM for "use of condom" into felt need and then felt need 

into expressed need/demand. A baseline survey was conducted in the first year, findings 

include out of 326 respondents were 70% Hijrahs (Eunuch), 8.5% Malshias (Masseur), 

4.5% Truck drivers, 17% others. Ninety seven percent Hijrahs and 26% Malshias were 

passive agents. One percent Hijras, 48% Malshias and all Truck drivers are active. 

Seventy nine percent MSMs are involved in sex for the last 5 years. Only 12% of passive 

MSM use condoms, 44% of clients of passive agents never use condoms; while only 26% 

active agents use condoms. Only 9% of MSMs were carrying condoms during the time of 

interview. These findings will be compared with the findings at the end of the project 

survey and effectiveness of the project would be determined. Then decision would be 

taken to expand the same or improved methodology and approach in other regions and 

also duration of the project in same area. 

POSTERS 


PP 1.28 

Incidence of Atypical Mycobacteria in sputum AFB positive patients with AIDS 

presenting at a Tertiary Hospital in Mumbai 

Dr Mohammad Khalid 

Dr Preeti Meshram 

senior resident and Lecturer,respectively at The Dept of Chest Medicine,Sir 

J.J.Hospital,Mumbai,India. 

Objectives 

1. Study the incidence of Atypical Mycobacterium in sputum positive patients with AIDS. 

2. Comparative study of clinical features, skin testing, radiographic findings between 

patients suffering from infection with Mycobacterium tuberculosis and those with infection 

due to atypical mycobacterium. 

Methods 

• 75 Patients infected with HIV who presented to Sir J.J.Hospital Mumbai from August 

2003 to August 2005 were included. 

• All patients had proven infection with HIV. 

• Had respiratory symptoms. 

• Were sputum AFB positive by Z-N stain on 3 consecutive samples. 

• Evaluation included history, clinical examination, Mantoux test, CXR, complete 

hemogram. 

• Sputum examination by DOTS method for AFB by Z-N stain. 

• Bronchoscopy with bronchoalveolar lavage which was subjected to AFB culture on L-J 

medium. 

• Mantoux test was done using 5 TU of PPD. An erythema and induration of > 5mm was 

taken as positive. 

• CD4 cell counts were done in all patients. 

Results 

1. Of 75 patients studied, 71 had Mycobacterium tuberculosis and 4 Atypical 

Mycobacterial infection, the diagnosis being established by BAL AFB culture and a 

battery of biochemical tests. 

2. This gives an incidence of Atypical Mycobaterial infections as 5.33%. 

3. Cough and fever were the 2 most common symptoms in all 75 patients, irrespective of 

the type of mycobacterial infection. 

4. 33.33% patients had lower lobe involvement, 20% had more than 1 zone involved and 

16% bilateral extensive involvement. Differentiation could not be made radiologically. 

5. 18 patients i.e. 24% were Mantoux positive. All patients of atypical Mycobacteriosis 

were Mantoux negative. 

6. 55% had CD4 counts 400 / mm 3 . 

7. Of those with Atypical Mycobacteriosis, 3 had CD4 counts < 200/mm 3 and 1 between 

200 -400 / mm 3 . 

8. Sputum and BAL subjected for culture yielded growth in L-J medium in the same week 

in all patients. 


9. 25 patients of M.tuberculosis and 2 of Atypical Mycobacterioses yielded growth in 4 th 

week. 23 patients with M.tuberculosis in 5th week. Of the remaining 2 with Atypical 

infection, 1 in 3 rd and 1 in the 5 th week. 

Conclusion 

1. All HIV patients should be screened for Pulmonary Tuberculosis. 

2. There has been a considerable increase in the incidence of Atypical Mycobacterial 

infection following the AIDS epidemics with a negligible % initially (i.e. 1 %) to 5.33% as 

noted in the present study. 

3. Patients with Atypical Mycobacterial infection are almost always negative for Mantoux 

test. 

4. Clinical and radiological differentiation of Mycobacterium tuberculosis and Atypical 

Mycobateria is difficult. 

5. Differentiation is mostly based on culture techniques and a battery of biochemical tests. 

POSTERS 


PP 1.29 

Developing Partnerships Between Non-Profit Health Providers and the Department 

of Health for the Delivery of Quality Primary Health Care, including those related to 

HIV and AIDS, in South Africa 

FN Mbatha 1 ; N Twenga 2 ; D Ramokgopa 3 ; GP Chili 4 ; L Ernest 5 ; FP Netshipale 5 ; 

JF Aguilera 5,6 

1 

Partnership for the Delivery of Primary Health Care including HIV and AIDS Programme 

(PDPHCP), KwaZulu-Natal Provincial management unit, Department of Health, South 

Africa 

2 

PDPHCP, Western Cape Provincial management unit, DOH, South Africa 

3 

PDPHCP, Limpopo Provincial management unit, DOH, South Africa 

4 

PDPHCP, KwaZulu Natal, District Programme Management Unit, DoH, South Africa 

5 

PDPHCP, National Programme Management Unit, Department of Health (DOH), Pretoria, 

South Africa 

6 

AEDES, Brussels, Belgium 

Objectives. The adult HIV prevalence rate in South Africa was estimated at 21.5% in 2004. 

Still a substantial part of the population in South Africa has no or reduced access to 

quality Primary Health Care (PHC) services. In addition, PHC delivery by non-profit 

organisations (NPOs) is often hampered by inadequate management and skills. We aim 

to establish partnerships between NPOs and Department of Health (DOH) to deliver 

quality PHC services, and in particular those related to HIV and AIDS, to the communities. 

Methodology. The programme is operational in 16 districts of 5 provinces. NPOs 

delivering PHC are contracted and funded. National, provincial and district management 

units support (1) institutional and management strengthening (2) NPOs staff and 

caregivers accredited training (3) implementation of a monitoring and evaluation (M&E) 

system to be integrated into the national District Health Information System, (4) evaluation 

of HBC costing models, and (5) operational research. 

Results. By April 2006, 139 NPOs were funded in Western Cape (WC) (n=55), Limpopo 

(n=32) and KwaZulu-Natal (KZN) (n=52). In WC over 21 months, a monthly median of (1) 

883 caregivers delivered home-based care (HBC) to 5,027 clients, (2) 591 new patients 

were admitted, (3) 82 died. Age distribution was >60 years (50%), 19-59 (44%) and

PP 1.30 

Community Response to HIV/AIDS:Empowering Comunities in HIV/AIDS 

Management 

Beatrice Chola (Mrs.) 

IUATLD (International Union Against Tuberculosis And Lung Disease) membership No: 

CU-0458126, Zambia National AIDS Network, Lusaka, Zambia 

Introduction 

Bwafwano HBC was established in 1996 as a community response to the increasing 

number of HIV cases in the Chipata area of Lusaka. Since inception, Bwafwano has 

carried out Preventive, Care and Support and Impact Mitigation Programs. One such 

program under the Home Based Care Program is the ART Adherence Support Program 

for PLWHAs. 

Objective 

To empower communities with skills in HIV/AIDS Management. 

Method 

Bwafwano employs an integrated approach in HIV/AIDS Management. The approach 

starts with Community Volunteers who identify chronically ill patients. These are refered to 

the centre for HIV Testing and if positive they are enrolled with the HBC Program. It is from 

here that they are refered to Government Health Centres for CD4 Count and started on 

ART. From the Government Health Centres, patients are refered back to Bwafwano for 

ART Adherence Support and monitoring. Currently, out of 2,372 PLWHAs enrolled with the 

program, 318 are on ART. Bwafwano has also trained Community Volunteers and Primary 

Caregivers as ART Adherence Supporters. Patients are also identified through the VCT 

Centre, Community Clinic and the Community Laboratory at Bwafwano. 

Results 

The results of the program include improved health status of PLWHAs, reduced mortality 

rate and patients that were almost on the verge dying now healthy and providing for their 

families, reduced stigma including the formation of a support group for PLWHAs. 

POSTERS 

Conclusion 

Empowering communities with skills in HIV/AIDS Management contributes to improved 

health condition of PLWHAs through adherence to ART. Communities should themselves 

be primary promoters of ART Adherence leading to improved community health. 


PP 1.31 

Pakistani Youth and their Risky Behavior on HIV/AIDS & Sexuality 

Dr Muhammad Hanif 

Dr Kulsoom Akhtar Pakistan 

This project is proposed to build critical awareness through information dissemination on 

HIV/AIDS & Sexuality among youth and the enable to lead a prosperous and happy life by 

practicing socio-religious values. 

Needs of the project 

The situation of the Pakistan is ostensibly worse in this regard, two main reasons follow 

the highlighted point. 

First of all, the low literacy rate and the lack of entertainment opportunities in the country, 

secondly the ignorance of the people about the subject (Lack of Awareness about the 

subject). However, in order to high light the importance of the preventing the disease, 

individuals, communities and the influential people need to be aware on the subject. 

Objectives 

To improve the sexual health of population, to address the issue of sexual violence, to 

address sexual knowledge and needs of adolescents, to provide care and support. 

Goal of the project 

To provide sufficient knowledge, change their attitude and attributes of their risky behavior. 

Results and Conclusion 

Poor sexual values and economic conditions have a broad impact on Pakistan overall 

health situation and increase the vulnerability of the youth population to the infection with 

HIV/STIs. It believed that their two major high risk behavior which are facilitating the 

spread of HIV/STIs in Pakistan. The first of these unsafe sex, which accounts for up to 

70% of Pakistan's reported HIV infection, the second high risk behavior which may 

greatly influences the young people by injecting the drug users. Youth should be involved 

in awareness raising campaigns. Peer education philosophy should be introduced. 

Local communities should be involved in training and need assessment sessions. 

Local resources should be mobilized. 


PP 1.32 

Models For Prevention & Treatment of PLWHA-Lessons From AMPATH (Academic 

Model for Prevention And Treatment of HIV/AIDS) Program In Western Kenya 

Gichoya Judy Wawira 

Moi University, School of Medicine, Eldoret, Kenya. 

Issues 

Management of PLWHA in Kenya is hindered by existence information disparities, high 

poverty levels, inadequate and inaccessible health care facilities hence need for 

research, education and improved service provision. This formed the basis of 

development of the AMPATH model. 

Description 

An inductive study using open ended questionnaires and interviews was carried out and 

the results recorded and analyzed. 

Lessons learnt 

AMPATH has a tripartite mission of patient care involving prevention & treatment, medical 

education and research. Established in 2001, there are 8 clinics with a patient base of over 

17,000 adults and children of whom nearly half are on ARVs. Enrollment into the program 

rises by 800 to 1000 patients per month. It has several programs. (a)PMTCT which 

carries out opt-out testing policy, programs fostering triple ART of pregnant women and 

formula feeding of newborns. (b)FPI(Family preservation Initiative) which trains patients in 

income and occupational skills to get the patients and their families back on their feet.(c) 

HAART & Harvest Initiative which include establishment of practical, low cost, highly 

productive farms to provide high quality food to HIV affected families. (d) AMPATH Medical 

records System which enables managers to build and evolve to meet current and 

projected needs by providing summary data and computer generated reminders to help 

guide care. It is used to establish the best protocols for managing HIV/AIDS in resource 

constrained environments and establish guidelines for treatment specific to Kenya. 

POSTERS 

Recommendations 

Development of working models of urban and rural HIV preventive and treatment services 

in the public sector should be encouraged in order to provide comprehensive care to 

PLWHA i.e. treatment and prevention of opportunistic infections, ART, psychosocial 

support, patient education and nutritional counseling and support 


PP 1.33 

Model based on a quantum algorithm for the study of HIV 

Alejandro León Julio Pozo 

Universidad Diego Portales Santiago Chile 

In this work we develop a model based on quantum algorithms to study the evolution of 

an epidemic. We apply the model to study the development of the HIV, to do predictions 

of infection in the population who does not have knowledge of the condition of infection. 

The model uses the analogy that exists between the quantum systems and the individuals 

in a population who suffers an epidemic. We represent the individuals for quantum 

systems of two levels (quantum bit) and the interactions between these individuals (who 

cause the infection) are represented by unitary transformations, and we divide the 

population who is studied in categories (in agreement to his behavior) and simulate the 

interaction between the individuals of the same category and between individuals of 

different categories. Our intention is to show results of the number of infected depending 

on the time for every category and for the total population, besides we analyze the impact 

in the evolution of the epidemic due to the interaction without the knowledge of the 

condition of infection on the part of the individuals. 


PP 2.1 

Analysis of polymorphism in the protease and reverse transcriptase genes of HIV 

type 1 CRF02_AG subtypes from drug-naïve patients from Saint-Etienne, France 

Philip Lawrence, Marie-France Lutz, Henia Saoudin, Anne Frésard, Céline Cazorla, 

Pascal Fascia, Sylvie Pillet, Olivier Delezay, Bruno Pozzetto, Frédéric Lucht and Thomas 

Bourlet 

Laboratory of Virology and Department of Infectious Diseases, GIMAP, University Hospital 

of Saint-Etienne, 42055 Saint-Etienne cedex 02, France 

Objectives 

The impact of the high polymorphism in the protease and reverse transcriptase genes, as 

recently described for CRF02_AG isolates of African origin, is still disputed. In this study, 

we examined the polymorphism of these genes in CRF02_AG strains recovered from 

drug-naïve patients, most of these of French origin, followed at the University Hospital of 

Saint-Etienne, France. The impact of this polymorphism on antiretroviral resistance was 

then studied in 22 CRF02_AG and 45 B infected patients, treated during a mean period 

of 25.5 months. 

Methods 

The first plasma sample detected positive for HIV-1 was used to compare sequences from 

31 CRF02_AG and 23 B strains. The response to HAART was evaluated by the 

quantification of HIV RNA load and CD4 cell count at 1, 3, 6, 12 and 24 months after 

starting therapy, and by the outcome of therapeutic failure events. 

Results 

The diversity of the sequence of the protease and reverse transcriptase genes of the 

CRF02_AG strains showed a statistically significant difference from the B strains when 

compared to subtype B consensus sequence(P

PP 2.2 

Analysis of Full-length HIV-1 subtype G molecular clones 

Esteves A* Freitas SP* 

*Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, LIsbon, 

Universidade Lusófona de Humanidades e Tecnologias, Lisbon, Portugal 

Genetic analysis of HIV-1 strains circulating in Lisbon, Portugal, demonstrated a high 

prevalence of non-B subtypes, with predominance of subtype G and circulating 

recombinant forms CRF02_AG and CRF14_BG. To better understand the origin and 

biology of subtype G viruses circulating in Lisbon, we constructed full-length proviral 

clones from AIDS patients infected with subtype G. 

Nucleotide sequences of the full-length genomes (nt 61 to 9190 on HXB2) and individual 

genes were aligned with corresponding sequences from representative HIV-1 strains, 

including all subtype G sequences available on databases, and neighbour joining 

phylogenetic trees were constructed. Tree topology showed that both near-full length 

sequence and individual genes were non-recombinant, forming a geographic cluster with 

Spanish sequences available at databases, supported by bootstrap values >97%, and 

branching away from other subtype G sequences. Nucleotide sequence analysis of the 

entire genomes were carried out to confirm that all HIV-1 structural, regulatory, and 

accessory genes were preserved. We did not identify any obvious inactivating mutations 

such as translational stop codons, frameshifts, premature truncations, or deletions in gag, 

pol, env, nef, rev, tat, vif, vpr or vpu. The LTR sequences were intact with motifs such as 

the two NF-kB binding sites, the three Sp1 binding sites, and the primer binding site 

preserved as well as the RNA packaging signal sequence. 

Preliminary assays performed with one of the clone obtained demonstrated high titers of 

p24 antigen on the supernatant of transfected 293T cells. However, subsequent 

infectivity assays performed with this supernatant and indicator cell lines suggest a poor 

productive infection of target cells. Additionally full-length subtype G molecular clones and 

sub genomic clones are currently being used on complementation rescue experiments. 


PP 2.3 

Broad neutralization of Human Immunodeficiency Virus Type 1 by monoclonal 

antibody against C2 region 

Apichai Sreepian, Chongrak Permmongkol, Nattaya Tanliang, Ruengpung Sutthent 

Department of Microbiology, Faculty of Medicine Siriraj Hospital, and Faculty of Medical 

Technology, Mahidol University, Bangkok, Thailand 

The linear peptide corresponding to conserved region C2 on gp120 was previously 

designed and synthesized as a short peptide (amino acid position 218-239). Then the 

activity of peptide was investigated and shown to inhibit neutralization activity of long-term 

nonprogressor sera against HIV-1 CRF01_AE primary isolates (PI) from Thailand 

(Sreepian et al., 2004). Consequently, we produced monoclonal antibody against C2 

peptide (mAbC2) by conventional method and investigated activity of this mAb by 

neutralizing laboratory strains of HIV-1; MN, IIIB and NPO3. We found that it could 

neutralize all laboratory strains approximately (IC50) at concentration 155.65+15.9 µg/ml. 

Furthermore, more primary isolates collected from Thailand have been investigated and 

found to be neutralized by mAbC2 at concentration 96+53.85 µg/ml. This study showed 

that mAbC2 could neutralize broadly laboratory strains and primary isolates and C2 

epitope might be a good candidate for vaccine. 

POSTERS 


PP 2.4 

The Cobas Ampliprep/Cobas Taqman 48 HIV-1 test is compatible with the Primagen 

dried fluid spot technology for viral load measurement 

Michel P. de Baar, John T. Dekker, Esther de Rooij, Vincent Geutjes, Suzanne Jurriaans#, 

Harm B. van Schijndel 

Primagen, Amsterdam, the Netherlands, and #Department of Human Retrovirology, 

Academic Medical Center, Amsterdam, the Netherlands 

Objective 

to develop and evaluate protocols to combine the Cobas Ampliprep/Cobas Taqman 48 

HIV-1 test with Primagen's proprietary dried fluid spot (DFS) technology. 

Methods 

HIV-1 negative whole blood (WB) and plasma (P) was obtained via the blood bank. For 

reconstruction experiments, the WB and P were spiked with various concentrations of a 

viral stock, of which the viral load has been determined by repetitive testing using the 

Cobas Amplicor HIV-1 v1.5. These samples were tested according to the manufacturer's 

protocol as well as spotted on the Primagen filter papers for comparisons. The DFS were 

dried on the air for at least 15 minutes and stored upon use. The spots were punched out 

of the filter by a manually operated puncher or by laser cutter. Nucleic acids were 

recovered from the spots by dissolving them in lysis buffer for at least 3 hrs at room 

temperature before quantifying on the Cobas system. The clinical P samples were 

obtained, with permission, from the clinic of the Academic Medical Center in Amsterdam. 

Results 

The lower limit of detection for DFS was 360 copies HIV-1 RNA per ml P, comparable with 

the standard protocol when corrected for an input of only 200 µl P (4 spots of 50 µl each). 

10 P samples with RNA levels varying from 3log10 to 8 log 10 were tested both directly and 

via DFS. After the correction for 1 ml input in the direct method and 200 µl input via DFS, 

the Pearson correlation coefficient was 0.996 (P

PP 2.5 

Evaluation of the Trugene GP41HIV-1 genotyping Kit (Bayer) in comparison with 

ANRS recommended method 

Vanna Geromel( 1 ), Patricia Pinson-Recordon ( 2 ), Bernard Masquelier ( 2 ), Hervé Fleury ( 2 ), 

Jean-Dominique Poveda( 1 ) 

1 

Laboratoire Pasteur Cerba, 95066 Cergy Pontoise cedex 09, France 

2 

Laboratoire de Virologie, CHU de Bordeaux, Groupe hospitalier Pellegrin, 33076 

Bordeaux cedex, France 

Objectives 

To compare the results obtained with the TruGene GP41 HIV-1 genotyping kit (Bayer) with 

the ANRS reference method on plasmas of HIV-1 infected patients from differents 

sub-types, on enfuvirtide (T20)-experienced and -not experienced patients. 

Methods 

22 plasma samples (10 subtype B, 8 subtype C, 4 subtype unknown) taken from 22 

patients, previously tested with recommended ANRS primers for HR1-HR2 region 

(www.hivfrenchresitance.org) and 7 samples from the ANRS annual proficieny panel (3 

subtype B, 3 subtype G, 1 subtype J, 1 negative) were blindly tested with the TruGene 

GP41 HIV-1 genotyping Kit (Bayer) according to the manufacturer's recommendations. 

Complete nucleotide and amino-acid sequences obtained were compared and mutations 

in the 36-45 amino-acids positions of HR1, clinically relevant according the ANRS 2005 

interpretation algorithm, were specifically investigated. 

Results 

All samples previously genotyped with ANRS primers were successfully amplified with the 

Trugene GP41 HIV-1 genotyping kit. One sample from the ANRS proficiency panel was 

negative with both methods. 

A concordance of 99.5% was obtained on the 5250 nucleotide positions of the 230 bp 

sequence assessed, and a concordance of 97.4% was obtained for the 189 amino-acids 

positions tested. A mixture (wild type/mutant) was found at 2 positions with the ANRS 

method and in 3 with the TruGene kit when the alternative method found either the wild 

type or the mutated amino-acid. No position was found to be a pure mutation with one 

method and a pure wild-type with the other. No discrepancy was obtained between the two 

methods in terms of resistance to T20 according to interpretation with the ANRS 2005 

algorithm. Mutations were found only in T20 experienced patients. 

POSTERS 

Conclusions 

The TruGene GP41 HIV-1 genotyping kit (Bayer) was very well correlated to the ANRS 

method taken as reference. It can be considered as suitable to a routine clinical use. 


PP 2.6 

Mutations and Polymorphisms in the gp41 of the HIV-1 from T20 Naive Patients 

Receiving HAART 

Carla Teixeira; Dercy Sá-Filho; Wagner Alkmim; Michelle Zanoni; Ricardo Diaz; Shirley 

Komninakis. 

Federal University of São Paulo - São Paulo City -Brazil 

Background 

In many patients with HIV infection, therapy with HAART does not result in complete 

suppression and leads to the failure. Like this, the development of new therapeutic 

alternatives is necessary. T-20 is a synthetic aminoacid that binds to the HR1 domain and 

inhibits entry of HIV-1 into host cells. The substitutions in GIV motif are critical, occurring 

resistance to T20. The study of primary mutations in HR1 domain are important to direct 

antiretroviral scheme in patients eligible to the T20 therapy. 

Methods 

61 HIV-infected patients with a CD4+T cell count10.000 copies/mL were eligible. The 

gp41 gene was amplified using a PCR nested and sequenced on both strands. We 

realized alignment by ClustalX and all sequences were submitted to Blast at Los Alamos 

HIV Sequence Database to the subtyping. Genetic diversity was performed by 

Tamura-Nei and Nei-Gojobori. 

Results 

Of the 61 samples 53 were of subtype B, 7 of the subtype F and 1 of the subtype C. 

Analysis of the aminoacids involved in resistance revealed that all had identical residues 

at critical 36(G), 37(I) and 38(V) positions. Other changes were detected in several 

positions such as, 225 (86,9%) occurred in subtype B, 29 (11,2%) in subtype F and 5 

(1,9%) in subtype C. We verify low diversity demonstrated for the value dn/ds of 0,18. 

Conclusions 

We verify the high conservation in GIV motif, indicating that primary T20 genotypic 

resistance is not frequent. On the other hand, we observe changes in some positions and 

this needs further evaluation. These findings provides the importance of the study of the 

gp41 region of the HIV-1 in patients failure in treatment with the HAART. T20 may be used 

in association with HAART and to represent a new treatment strategy. 


PP 2.7 

Development of the Oligonucleotide Ligation Assay for the Detection of the M184V 

Mutation Associated with Resistance to Lamivudine in HIV-2. 

S Jallow 1,2 , S Kaye 1 , M Schutten 3 , S Rowland-Jones 1 , W Janssens 2 . 

1 

Department of Virology, Medical Research Council Laboratories (MRC), Banjul, The 

Gambia. 

2 

Department of HIV Virology, Institute of Tropical Medicine, Antwerp, Belgium. 

3 

D Erasmus Medical Center, Institute of Virology, Rotterdam, The Netherlands. 

Backgroung 

The Oligonucleotide ligation assay is a point mutations assay based on the covalent 

joining of two adjacent differentially labelled oligonucleotide probes by a DNA ligase when 

they are hybridized to a complementary DNA template. Ligation occurs between the 

common oligonucleotide probe and either the WT (wild type) or mutant probe and the 

ligated product is then captured on steptavidin-coated plates and then detection can be 

done by ELISA. 

Though genotyping is mostly done by sequencing, the Oligonucleotide ligation assay has 

been shown to be more sensitive, simple, rapid and economical without need for 

expensive equipment and technical expertise. Thus this assay is more sustainable for use 

in resource-poor settings 

Methods 

A set of 3 Oligonucleotide probes, common, wild type and mutant were developed for the 

M184V mutation. Reference plasmids were composed to serve as HIV-2 mutant and wild 

type controls by cloning PCR amplicons of viral isolates with the mutations of interest into 

a plasmid. The Protease and RT of 60 HIV-2 samples were amplified from plasma and 

then sequenced. HIV-2 OLA was developed for M184V and then evaluated on 60 HIV-2 

samples from patients who were either treatment naïve or have been on ART. OLA results 

were compared with sequencing. 

POSTERS 

Results 

HIV-2 OLA was successfully developed for the M184V mutation. The sensitivity of 

detection of M184V was 100% by sequencing and 96.7% by OLA. Four discordant results 

between OLA and sequencing were detected: OLA could not genotype 2 samples 

(indeterminate results) that were genotyped by sequencing. These two samples had a T 

instead of a C at the first base after the ligation site, interfering with the ligation process. 

For the other two samples, sequence data gave a M184I genotype, but OLA resulted in 

wild type viruses for one sample and a mixture of mutant and wild type viruses for the 

other sample. 

Conclusions 

We have developed a simpler, more economical and sustainable assay than sequencing 

for the detection of the M184V resistance mutation in HIV-2 infected patients that would 

be more appropriate for use in resource-poor settings. Further optimisation of the probes 

will be done to reduce the occurrence of indeterminate results. 


PP 2.8 

Differences in the phenotypic profile of T cell subsets between Long Term 

Asymptomatic HIV and HIV treated patients in virological success could contribute 

to delay the disease progression 

C. Brunet 1 , P. Colson 2 , N. Bardin 1 , I. Ravaux 1 , I. Poizot-Martin 3 , H.Gallais 1 , C. Tamalet 2 and 

F. Dignat-George 1 . 

1 

CHU Conception Marseilles France, 2 CHU Timone Marseilles France, 3 CHU Ste 

Marguerite Marseilles France 

Background 

A minor proportion of HIV infected patients, termed long term asymptomatic HIV infected 

patients (LTA) remain healthy and immunologically stable in spite of HIV infection for more 

than 7 years and the absence of antiretroviral therapy. An extensive immunophenotypic 

pattern of markers of differenciation, functionality and activation on peripheral blood T cells 

has never been investigated for LTA patients. In this study, 11 LTA patients with plasma 

HIV-1 RNA (VL)

PP 2.9 

Immune restoration under HAART in patients chronically infected with HIV-1: 

diversity of HIV avidity and T, B and NK immune responses 

H. Le Guillou-Guillemette 1 , G. Renier 3 , B. Vielle 4 , P. Abgueguen 5 , J-M. Chennebault 5 , 

F. Lunel 1 , C. Payan 1,2 . 

1 

Laboratoire de Bactériologie-Virologie Centre Hospitalier Universitaire d'Angers, 4 rue 

Larrey, 49033 Angers cedex, France. 2 Département de microbiologie,Centre Hospitalier 

Régional Universitaire de Brest, Hôpital Morvan, 2 avenue Foch, 29609 Brest cedex 

3 

Laboratoire d'Allergologie-Immunologie Centre Hospitalier Universitaire d'Angers, 4 rue 

Larrey, 49033 Angers cedex, France. 4Service de Biostatistiques Centre Hospitalier 

Universitaire d'Angers, 4 rue Larrey, 49033 Angers cedex, France. 5 Service des Maladies 

Infectieuses Centre Hospitalier Universitaire d'Angers, 4 rue Larrey, 49033 Angers cedex, 

France. 

Objectives 

The aim of the study was to follow prospectively the humoral, cellular and innate immune 

responses under HAART and to verify if a functional restoration of the B lymphocytes 

could be evaluated by measuring the anti-HIV-1 IgG antibodies avidity index (AI). 

Methods: Eleven HIV-1 infected and immunosuppressed patients were included in the 

study. Viral load, naïve and memory B-cells, CD4 and CD8 T-cells and NK-cells counts, 

and anti-HIV-1 IgG AI were determined during the follow-up (18 months). 

Results 

Ten patients were sustained responders under HAART and showed a quantitative 

restoration of the CD4 T-cell counts (+269 x 106/L). The AI decreased for ten subjects 

(-11%, p=0.006) but very slowly and continuously. A quantitative restoration of the 

humoral immune response began, mainly concerning the naïve B-cells (+110 x 106/L). 

Apart from one patient, the CD8 T-cell subset approached the reference values of healthy 

subjects either by decreasing or increasing their cell levels. No homogeneous evolution 

was described concerning the NK-cell subset, apart from trend towards increasing in 

patients with opportunistic infection (range, +58 to +291 x 106/L). 

POSTERS 

Conclusion 

Our study, which evaluated simultaneously for the first time to our knowledge the cellular, 

humoral and innate immune responses showed that HAART induced a large diversity of 

immune restoration patterns in responder patients. However, the AI measure appears to 

be a weak marker to evaluate an immune restoration in chronic HIV-1 infected patients 

under HAART. 


PP 2.10 

Biochemical Characterization of mycobacterial phosphoglucose isomerase and its 

mutants 

Divya Mathur, Zaid ahsan,MadhulikaT iwari and L.C. Garg 

Gene Regulation Lab, National Institute of Immunolgy, Aruna Asaf Ali Marg,New Delhi-67, 

India 

Phosphoglucose isomerase (PGI) is a well characterized ubiquitous enzyme involved in 

the glycolytic pathway. It catalyses the reversible isomerization of D-glucopyranose-6- 

phosphate and D-fructofuranose-6-phosphate and is present in all living cells. PGI shows 

very low sequence homology across species, however, some of the residues remain 

highly conserved. The Available crystal structures of PGI form various species have 

shown that though the basic structure of the enzyme remains similar, mammalian and 

bacterial PGIs vary in active site conformation and relative arrangement of loops and 

helices. The present study was undertaken to characterize the mycobacterial PGI, a key 

regulatory enzyme of glycolysis that is central to the organism's survival and 

consequently a potential drug target. For this purpose, the gene encoding the PGI from 

Mycobacterium tuberculosis H37Rv was cloned in pET-22b(+) vector and expressed in E. 

coli. Further, to evaluate the role of crucial amino acid residues, site directed 

mutagenesis was carried out targeting each identified residue to generate mutant 

proteins. Wild type (WT) as well as the mutant recombinant PGI (rPGI) expressed partly 

as soluble proteins and partly as inclusion bodies. WT and mutant rPGIs from soluble 

fraction were purified to near homogeneity by Ni-NTA ion-exchange chromatography and 

characterized. Mycobacterial PGI exhibits catalytic and biochemical properties belonging 

typically to enzymes of the PGI superfamily. The enzyme is a homodimer, the Km of rPGI 

was determined as 0.27±0.03 mM for fructose-6-phosphate and Ki was 0.75 mM for 

6-phosphogluconate. The rPGI had optimal activity at 37°C and pH 9.0 and did not 

require mono or divalent cations for its activity. The specific activity of recombinant 

enzyme was 600 U/mg protein. 

Investigations with mutant proteins revealed that mutation at T212 resulted in a loss in 

enzyme activity with an increased Km, suggesting its involvement in the initial binding of 

substrate and not in catalysis. Replacement of G156 with bulky tyrosine resulted in 

complete inactivation of the enzyme, indicating its role in maintaining the active site 

architecture. Replacement of N314 by arginine appears to interfere with electrostatic 

charges on protein surface as evident by the aggregation of the mutant protein. 

Replacement of G360 with glutamic acid did not affect kinetic and catalytic properties of 

the enzyme, however, reduced the stability of the enzyme to thermal denaturation. 


PP 2.11 

Whatman FTA Cards, designed for collection, transport, archiving and isolation of 

nucleic acids at room temperature, inactivate human immunodeficiency virus type 

1 (HIV-1) and BVDV (model virus for Human Hepatitis C virus). 

Penezina O., Neal H. 

Whatman Inc., 63 Community Drive, Sanford, ME, 04073, USA. 

Objective 

To demonstrate that Whatman FTA cards, designed for collection and transport of nucleic 

acids at room temperature could inactivate human immunodeficiency virus type 1 (HIV-1) 

and BVDV (HCV model) virus. 

Methods 

HIV-1 (HTLV-IIIB strain) was titrated in-vitro by CEM-A syncytium assay. The HIV-1 stock 

solution used in the current study tested positive for identity by negative stain electron 

microscopy and p24 analysis and was free of potential bovine and porcine viral 

contaminants. 

Human blood was spiked with 10% of stock virus solution. An aliquot of the spiked human 

blood was immediately tested as T0 sample. Another aliquot was incubated at 22+5 C for 

the duration of the FTA Treatment Step (60 minutes) and tested as a Processing Control. 

Treatment FTA samples were generated by applying of 125 microliters of spiked blood 

onto FTA cards from 4 different lots (3 lots of indicating and 1 lot of non-indicating FTA 

cards). At 60 minutes following the initiation of incubation, 6 ml of virus resuspension 

media was added to each blood stain card. Serum-free media served as a negative 

control for the titration study. 

Upon initiation of viral titrations, one aliquot of each test and control sample was diluted in 

serum-free medium as appropriate and assayed by the standard virus titration procedure 

(in multiple wells for infectious viral particles using CEM-A indicator cells). 

The BVDV stock solution used in current study tested positive for identity when 

challenged with polyclonal antisera specific for BVDV and was free of potential bovine, 

porcine and equine viral contaminants. The titer of the production lot of virus used in the 

study was determined by a plaque assay utilizing BT indicator cells. 

POSTERS 

Application of blood spiked with 10% of stock BVDV virus solution to FTA cards was 

identical to one described for HIV-1 study (see above). 

Upon initiation of viral titrations, one aliquot of each test and control sample was diluted in 

serum-free medium as appropriate and assayed by the standard virus titration procedure 

(in multiple wells for infectious viral particles by BVDV plaque assay using BT indicator 

cells). 

Results 

Upon 60 minutes contact of HIV-1 spiked human blood with Whatman FTA cards, the virus 

was reduced to non-detectable levels in all FTA card samples resulting in virus Log10 

reductions greater than 2.33-2.81 depending on the lot tested (95% confidence interval 

was calculated according to the ICH Topic Q5A). 


Upon 60 minutes contact of BVDV spiked human blood with Whatman FTA cards, the 

virus was reduced to non-detectable levels in all FTA card samples resulting in virus Log10 

reductions greater than 4.09 depending on the lot tested (95% confidence interval was 

calculated according to the ICH Topic Q5A). 

Conclusions 

Whatman FTA cards inactivate human immunodeficiency virus type 1 

(HIV-1) and BVDV (model for human Hepatitis C virus) at room temperature and 

therefore could be safely used for collection, transport, archiving and isolation of nucleic 

acids from patient samples infected with HIV-1 or human Hepatitis C virus. 


PP 2.12 

Cellular immune response to Cryptosporidium parvum in Cryptosporidium-HIV 

co-infected patients 

Kirti Kaushik, Sumeeta Khurana, Ajay Wanchu*, Nancy Malla 

Kirti Kaushik, Sumeeta Khurana, Ajay Wanchu*, Nancy Malla 

Dept.of Parasitology and Internal Medicine*, PGIMER, Chandigarh, India 

Acquired Immuno Deficiency Syndrome (AIDS) is a global emergency with far reaching 

effects. The gastrointestinal tract is a major target organ in HIV related opportunistic 

infections, which persists, commonly as diarrhoea. Cryptosporidia are increasingly being 

recognized as important enteric pathogens in AIDS and other immuno-suppressed 

patients. The host immune responses that prevent the initial infection by Cryptosporidium, 

limit its spread and ultimately facilitate its clearance are poorly understood .Since data on 

immune response to Cryptosporidia in HIV patients co-infected with Cryptosporidium are 

lacking, the present study was designed to assess the cellular immune responses in the 

HIV patients infected with Cryptosporidia. For this PBMCs separated from the patients 

were proliferated in the presence of Cryptosporidium parvum crude soluble antigen (CCA) 

and proliferation was measured by counting the thymidine incorporation into the cells. 

PBMCs from the Cryptosporidium infected patients (both HIV infected and non-infected) 

showed high proliferation against CCA as compared to Cryptosporidium non- infected 

subjects. 

POSTERS 


PP 2.13 

Assessing the Contribution of CD8+ T Cells among TB Case-Contact Cohort Using 

Fresh EX-VIVO Elispot Readouts 

Lugos MD, Hammond AS, Adegbola RA and Brookes RH 

MRC Laboratories, The Gambia 

The IFN-γ secreting T cells have been reported to play a central role in protective 

immunity against TB. Whilst the role of CD4+ T cells is crucial, recent evidence suggests 

IFN-γ secreting CD8+ T cells may also have a key role in control of latent or chronic MTB 

infection. 

Our objective is to assess the contribution of CD8 + T cells in TB immune response using 

ELISPOT readouts from TB Case-Contact cohort. 

We employed novel tetrameric antibody cocktail (RosetteSep) to deplete CD8 cells 

directly from whole blood. Fresh ex vivo ELISPOT assay was carried out using depleted 

and undepleted PBMC from TBCC cohorts to determine the proportion of circulatory 

effector T cells. Flow cytometry was used to determine the percentage purity of cells 

depleted. 

Results show variable drops in PBMC count ranging from 5.26 - 77.14%. Despite this, a 

98% depletion success was obtained for CD8+ T cells, while 59.4% enrichment was 

observed for the CD4 fragment. Further, we observed a comparable increase in IFN--γ 

producing cell frequencies as an indication of enhanced CD4 response. Responder 

frequencies of CD8 depleted fraction showed a decreased trend, with those responding to 

ESAT-6 having a higher count among cases than contacts. 

We therefore conclude that TB cases tend to show more of CD8 immune responses. 

Hence, the appearance of CD8+ T cell response could be used as a marker for progression 

to disease amongst the infected TB contacts. 


PP 2.14 

CD4 Independent Transmission of HIV 

A.H. Bandivdekar, Shilpa Velhal and 

V. P. Raghavan 

National Institute for Research in Reproductive Health, 

J. M. Street, Parel, Mumbai 400 012 INDIA 

Objectives 

To identify and characterize CD4 independent HIV receptor on spermatozoa. 

Methods 

Human sperm proteins were solubilized using 1% Triton X-100. The HIV binding protein 

was identified by Western blot analysis of sperm proteins using gp120 HIV env 

glycoprotein, antibodies to gp120 and alkaline phosphatase labeled antirabbit IgG. The 

differential expression of 160kDa protein in the sperm samples from different individuals 

was studied by Western blot and flow cytometric analysis. cDNA encoding 160kDa protein 

was isolated from human testicular cDNA and sequenced. 

Results 

Western blot analysis of sperm proteins demonstrated the specific binding of gp120 as 

well as cell free HIV to 160kDa protein band. 160kDa protein has been shown to be 

distinct from conventional CD4 receptor. The preliminary studies demonstrated the 

differential expression of this protein in sperm samples from individual donors and the 

samples which are devoid of this protein did not show the binding of gp120 HIV envelope 

glycoprotein to any of the protein in sperm extract. cDNA sequencing of 160kDa HIV 

receptor protein showed sequence homology with human mannose receptor. 

Conclusion : Human immunodeficiency virus (HIV) is known to be primarily transmitted 

through sexual route. Although initially seminal leukocytes and cell free virus were 

suspected to be the source of infection, later it is realized that HIV binds and enter in to 

spermatozoa and the sperm bound virus facilitate the infection into urogenital cells such 

as Langerhan cells and Macrophages. Moreover the studies using monkey model 

demonstrated that the due to acidic vaginal pH the survival of seminal leukocyte as well 

as cell free virus is difficult and the cell free virus need for efficient infection through 

vaginal route is very high as compared to that of systemic route. Hence understanding the 

role of spermatozoa in transmission of HIV is important. However the modality of HIV entry 

into spermatozoa was not known due to absence of conventional CD4 receptors on 

sperm. In an attempt to understand the mechanism of HIV transmission, CD4 independent 

160kDa HIV receptor protein present on the spermatozoa has been identified for the first 

time, which showed the sequence homology to human mannose receptor. The differential 

expression of this protein on the sperm samples from different individuals may be 

associated with the risk of sexual transmission of HIV. These observations suggest the 

need for renewed efforts towards the development of modalities in prevention of sexual 

transmission of HIV and also need to understand mechanism of CD4 independent 

interaction of HIV. 

POSTERS 


PP 2.15 

Correlation between circulating viral load and HIV-1 detection in the sperm of HIV-1 

positive patients consulting for Medically Assisted Procreation 

E.Moens, C.Liesnard, Y.Englert 

C.Liesnard: Service de Virologie, Hôpital Erasme et Laboratoire de Référence SIDA de 

l'ULB, 1070 Bruxelles, Belgique Y.Englert: Service de Gynécologie/Obstétrique, Hôpital 

Erasme et Laboratoire de Recherche en Reproduction Humaine de l'ULB, 1070 Bruxelles, 

Belgique 

Objectives 

Within the framework of a program for medically assisted procreation of serodiscordant 

couples, we decided to analyze the factors that may predict the HIV-1 presence in the 

sperm of HIV-1 positive men as well as in its various fractions. 


168 pairs of blood and sperm samples coming from 46 HIV-1 positive men followed for 

medically assisted procreation were analyzed in parallel. The sperm of these patients and 

its various fractions (seminal plasma, seminal liquid and final solution of density gradient 

and swim up sperm wash) were tested by qualitative nested PCR researching for viral 

RNA (detection threshold of 20 ARN HIV-1 copies per ml). The blood viral load and the 

rate of CD4+ lymphocytes per mm3 of blood plasma were quantified at the time of each 

sperm sampling. 

Results 

• The presence of HIV-1 is respectively detected in 14,6% (24/164), 19,7% (30/152) and 

21,4% (34/159) of the fresh sperm, seminal plasma and seminal liquid samples as well as 

in 3% (5/165) of the final sperm wash solutions. The blood viral load is detected in 42,7% 

(70/164) of the cases. 

• There is a blood viral load significantly higher at the time of the virus detection in the 

sperm (p = 0,002), seminal plasma (p = 0,001) and seminal liquid (p = 0,002) of these 

patients. Indeed, an increase in the frequency of the virus detection in the sperm and its 

various fractions is observed according to the blood viremia of the patients. 

• No correlation was observed between the numeration of CD4+ blood cells and the 

secretion of virus in the sperm and its various fractions. 

• In the same way, the rate of round cells present in sperm does not seem to affect the 

frequency of virus detection taking into account a population of non-coinfected patients 

(rate of round cells always in the standard). 

• 3,2% (3/94) of the patients presenting a undetectable blood viremia (< 50 copies of ARN 

HIV-1 per ml of blood plasma) keep identifiable virus in their sperm. 

• 16,7% (4/24) of the fresh sperm samples that were detected positive at the time of the 

sampling remain positive even after sperm wash. These samples come from patients with 

high viral load (> 10000 copies of viral ARN per ml of blood plasma). 

Conclusions 

In the context of patients consulting for medically assisted procreation, the plasmatic viral 

load proves to be one of the factors significantly influencing the excretion of the HIV-1 in 

sperm and its various fractions. Wowever, this correlation presents exceptions reinforcing 

the interest of a systematic research of the virus in the sperm before its use within the 

framework of medically assisted procreation. 


PP 2.16 

Possible 'Suicide Inhibition' by Peptide Oligomeres of HIV-1 Protease Inhibitors 

Hans J.Schramm, Wolfgang Schramm 

Dept. Haemostaseology, LMU, Ziemssenstr. 1, 80336 München 

All protease (PIs) used in AIDS therapy target the active site. Some peptides derived from 

the terminal PR segments, however, act by dissociating the PR dimer into inactive 

subunits ("dimerization inhibitors"). Good inhibitors of this type are lipid-blocked 

tripeptides, e.g. Palmitoyl-Tyr-Glu-(thyronine)-OH, Ki ~5 nM [1,2], mimetics are in 

development. Interface targeting PIs should inhibit therapy mutants. 

However, peptidic compounds do not easily penetrate the cell membrane of lymphocyte. 

If it were possible to stimulate the cells to synthesize such peptides, the problem would be 

solved. One way to achieve this goal, is to introduce into cells carriers of genetic 

information to synthesize oligomeres of the peptidic PIs which contain PR cleavable 

sequence segments. In the infected cells - and only in those - the peptide oligomeres 

would be cleave by the specific PR and the inhibitory peptides set free. This would mean 

that the genes would have to be introduced, e.g. by virus-like particles. 

In order to identify suitable peptide oligomeres, a computer program for cleavage 

prediction [3] was used. Peptides were found with cleavage segments on both, the N- and 

C-terminal ends, and with sufficient inhibitory potential. A first set was synthesized and 

tested in an PR enzyme assay using a chromophoric substrate [1]. The IC(50) values of 

the peptides are: 

H-Tyr-Glu-Ile-Ser-Tyr-Glu-Leu-OH , 0.31 µM (competitive inhibition), 

H-Tyr-Glu-Phe-Ser-Tyr-Asp-Leu-OH, 0.05 µM ( "mixed inhibition"), H-Tyr-Glu-Ile-Ser-Tyr- 

Asp-Leu-OH, 0.16 µM, 

H-Tyr-Glu-Ile-Ser-Tyr-Asp-Trp-OH, 1.2 µM, 

H-Tyr-Lys-Ile-Ser-Tyr-Asp-Trp-OH, 7 µM, 

For the last 3 peptides the mode of action has not been established. 

In these oligomeric peptides, scissile segments are present, e.g. for the second peptide: 

--Tyr-Asp-Leu-!-Tyr-Glu-Phe-Ser-Tyr-Asp-Leu-!-Tyr-Glu-Phe-- . 

The third peptide of the list acts partly as a dimerization inhibitor ("mixed inhibition" 

according to Zhang [1]) silencing also mutant PR. Also active site inhibition would be 

valuable, however. Both inhibitors together could be applied if medical application turns 

out to be possible. Since many inhibitor copies arise after cleavage, a mediocre inhibitory 

power is no problem. The short life time of peptides in the cells would also be overcompensated 

by the large number of copies and the permanent re-synthesis. 

Improvements of this 'suicide inhibition' can be expected, e.g. by longer peptides. 

POSTERS 

1) Schramm, H.J. et al.. Biol. Chem. (99) 380, 593-596. 2) Dumond, J. et al.. Biochem. 

Pharm. (03) 65, 1097-1202. 3) Chou, J.J. (93). J. Protein Chem. 12, 291-302. 


PP 2.17 

Interface targeting peptides as inhibitors of HIV-1 protease 

Schramm, Hans J., Schramm, Wolfgang 

Dept. Haemostaseology, LMU, Ziemssenstr. 1, 80336 München, Germany 

While most inhibitors (PIs) of HIV protease (PR) target the active site, some peptides 

derived from the terminal segments act by dissociating the PR dimer - a ß-sheet 

interface structure - into inactive subunits ("dimerization inhibitors"). The modes of action 

can be distinguished by kinetic analysis from other inhibition modes. From these peptides, 

highly active PIs were developed [1-3]. The best inhibitors are lipid-blocked tripeptides 

with C-terminal thyronine (T0) or thyroxine (T4), e.g. Palmitoyl-Tyr-Glu-(Tx)-OH with Ki ~5 

nM [2]. Tyr and (Tx) are anchor residues. They seem to be the most potent specific 

reagents for protein/protein dissociation and also of interest for 'interactome' projects. 

Since large side chains as in thyronine do not fit into the active site sub-sites of dimeric 

PR, the dissociative mechanism is proved. The cell pH of 7.4 also lowers dimer stability. 

Interface targeting PIs should also inhibit therapy mutants since the interface is well 

conserved and mutants (e.g. V82T) have lower dimer stability. Some of the inhibitors 

(Pam-YET0) abrogate viral replication, but only few have been tested so far. Tests using 

PI-resistent virus strains are under way. There is a good chance to convert the peptides 

into cheap "modified peptides" and mimetics (peptoids, ester prodrugs, retro-inverso, 

cyclic and D-form peptides [3]). Some triterpene and steroid derivatives with low toxicity 

(ursolic, oleanolic acids, ursodesoxycholic acid) also inhibit PR in this way [4] and may be 

useful in cocktails. 

Some PIs interact also with other beta-sheet proteins like beta-secretase or amyloid 

aggregates (Alzheimer Aß). Vice versa, PR is inhibited by beta-sheet insertion peptides 

from serpin enzymes (Ac-AMFLEAIP-Nle-E from a1-Antitrypsin (IC50 25 µM) containing 

the inhibitory TLNF sequence) [5]. This suggests that endogenous proteins may be able 

to interfere with the dimerization of PR or other HIV proteins, in this way modulating 

disease progress. Similar PR cleavage and inhibitor sequences occur in virus and cell 

proteins, e.g. p6*, endogenous retroviruses, proteins Q8NA00, FLJ360 (VSYSF), etc.. 

1) Schramm, H.J. et al.. Biol. Chem. (99) 380, 593. 2) Dumond, J., et al.. Biochem. Pharm. 

(03) 65, 1097. 3) König, S., et al. (03), in: R. Epton (Ed.). Mayflower W.W., Proc. 6 th Int. 

Symp. Solid Phase Synth. 24, 107. 4) Quéré, L. et al. (96), B.B.R.C. 327, 484. 5) 

Schramm. H.J (04). J. Peptide Sci., Supplement H74. 


PP 2.18 

Inhibition of HIV Protease by Triterpene-Amino Acid Conjugates 

Luc Quéré 1 , Stephan König 2 , Wolfgang Schramm 3 , Hans J.Schramm 3 . 

1 

UCB Pharma, 1420 Braine L'Alleud, Belgium. 2 Biontex Laboratories, D-80807 München. 

Germany; 3 Dept. Haemostaseology, LMU, Ziemssenstr. 1, D-80336 München, Germany. 

Peptides derived from the terminal segments of HIV protease (PR) inhibit PR activity by 

dissociating PR into inactive monomers ("dimerization inhibitors") [1-3]. The modified 

inhibit PR (e.g. Palmitoyl-Y-E-(thyronine)-OH, ~5 nM). Starting from computer modeled 

PR-inhibitor complexes, a pharmacophoric structure was defined for PR inhibitory 

structures. By screening through the CSD (Cambridge Structural Databank) triterpene 

(and steroid) structures were identified [4] matching the pharmacophore elements. 

Ursolic, betulinic and oleanolic acids were among the most potent triterpenes in the 

enzyme test with kinetic constants of 3.4 µM (Ki), 2.5 µM (IC50) and 2.0 µM (Ki), 

respectively, with dimerization inhibition mode for oleanolic and ursolic acid. These 

well-tolerated triterpene scaffolds warrant further investigations. In order to improve 

inhibition and bio-availability of the compounds, blocked 3-OH ester derivatives were 

synthesized. After protection of the triterpene carboxylic group, the OH-3 group was 

blocked by succinic anhydride and the obtained acids reacted with the (protected) amino 

acids Ile, Lys and Glu. In this way, derivatives were obtained with positive and negative 

charge and a hydrophobic side-chain. Deprotection reestablished the free triterpene 

carboxyl group. The anti-PR activity tests showed that esterification of ursolic acid 

retained some activity (IC50 = 15 µM). Intermediates with t-Boc blocked groups were 

insoluble. The activity is lost in the lysine derivative (IC50 >50 µM). The acidic and 

hydrophobic derivatives, however, retained or improved activity (IC50 values: Ile 3.0, Glu 

1.0 µM). 

It is not clear whether the metabolic stability of the sterically blocked and rather stable 

esters is sufficient for a medical application. Since the basic triterpenes are moderate 

inhibitors already [4], use may be beneficial already through these agents. Improvement 

of stability could be obtained by the use of a-di substituted esters in position 3, i.e. 

dialkyl-succinic or -glutaric acid. In any case, the result showing PR inhibition 

improvement by a negative charge in this structural part may point a way to obtain other 

useful - also non-ester? - derivatives of triterpenes. 

There is report about the dimethylglutarate of betulinic acid as a potent "maturation 

inhibitor" of unknown mechanism (now in Phase II test, www.panacos.com); there, no PR 

inhibition was found [5] although relatively high amounts of the PR toxic DMSO were 

added in tests. From our results with similar structures (ursolic acid succinate), this 

betulinic acid derivative should show PR inhibition. 

1) Schramm, H.J. et al.. Biol. Chem. (99) 380, 593-596. 2) Dumond, J. et al.. Biochem. 

Pharm. (03) 65, 1097-1202. 3) König, S., et al. (03). In: R. Epton (Ed.), Mayflower 

Worldwide. Proc. 6th Int. Symp. Solid Phase Synth. 24, 107-114. 4) Quéré, L. et al. (96) 

B.B.R.C. 327, 484-488. 5) Li, F. et al. (03) PNAS 100, 13555-13560. 

POSTERS 


PP 2.19 

HIV-1 gene expression: lessons from provirus and non-integrated DNA 

Yuntao Wu 

Center for Biodefense, Department of Molecular and Microbiology, George Mason 

University, Manassas, USA 

Replication of HIV-1 involves a series of obligatory steps such as reverse transcription of 

the viral RNA genome into double-stranded DNA, and subsequent integration of the DNA 

into the human chromatin. 

Integration is an essential step for HIV-1 replication; yet the natural process of HIV-1 

infection generates both integrated and high levels of non-integrated DNA. Although 

proviral DNA is the template for productive viral replication, the non-integrated DNA has 

been suggested to be active for limited viral gene synthesis. In this review, the regulation 

of viral gene expression from proviral DNA will be summarized and issues relating to 

non-integrated DNA as a template for transcription will be discussed, as will the possible 

function of pre-integration transcription in HIV-1 replication cycle. 


PP 2.20 

Inhibitory Activity and Protein Profile Characterization of Supernatant from 

Placental Macrophages 

Katia E. Garcia-Crespo 1 , Vivian Garcia 1 , Loyda M. Melendez-Guerrero 1 

1. University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico 00935 

Background 

It is well documented that soluble factors secreted in the placenta are able to inhibit viral 

replication. Studies done recently in our laboratory have shown that supernatant from 

placental macrophages (PM) is capable of reducing viral replication in monocyte derived 

macrophages (MDM). In this study we test the hypothesis that the factors responsible for 

the inhibition of viral replication are produced constitutively by PM. We also propose that 

PM and MDM express different proteins and that the proteins expressed at higher levels 

by PM are likely candidates to be the factors responsible for the inhibitory activity. 

Methods 

To determine if the factors found in the supernatant are produced constitutively or if they 

need to be accumulated over a certain amount of time in culture, PM were isolated from 

term placenta and cultured for collection of supernatants at days 3,6,9 and 12. MDM were 

infected with HIV-BAL and cultured with the collected supernatant or with medium alone 

as a positive control. HIV p24 antigen assays were done to detect the effect of 

supernatant on viral replication. We also characterized the protein profiles of PM and 

MDM supernatants using four different chips (CM 10, Q10, IMAC30 and H50) to 

determine which of the surfaces are better to observe protein expression. PM and MDM 

were cultured and supernatant was collected at day 12. This supernatant was then 

analyzed using SELDI-TOF technology from Ciphered to obtain a protein profile. Results: 

We found a reduction in HIV-1 replication in MDM cultured with PM supernatant from days 

6, 9 and 12 as compared with the positive control. We compared the protein profiles from 

MDM and PM supernatants analyzed on four different surfaces and found that the anion 

exchange (CM10) and metal affinity (IMAC30) surfaces were the best to observe protein 

expression in supernatants. We then analyzed samples from various PM and MDM 

supernatants on the CM10 chip and found differences in protein expression between the 

two groups. Conclusions: These results point out differences between PM and MDM 

supernatants. The HIV infectivity assay shows that PM supernatant collected after day 3 

suppress viral replication in MDM. These results suggest that supernatant needs to 

accumulate to exert its effect and that supernatant from day 12 is HIV inhibitory. The 

proteomic analysis shows that PM and MDM secrete different proteins. We hypothesize 

that at least one of the proteins secreted by PM could be a factor associated with the 

antiviral activity of the supernatant. 

POSTERS 


PP 2.21 

Vesical Cancer and Papillomavirus : Homology between bovine Papillomavirus type 

2 (BPV-2) E6 and mdm2 oncogene 

Caprani A *, Tran MKG* 1 

*Association "Positifs", Paris 1 Université Paris V 

Introduction 

Metastatic bladder cancer are not easily to treat. More fundamental researches are 

necessary to understand their physiopathology. Among the environmental causes (aniline, 

tobacco), viruses are paucily explored. Campo M.S. has demonstrated that bladder 

cancer occurs spontaneously in Scottish cows infected with BPV-2 and can also be 

induced experimentally by BPV-2. 

Objective 

To elucidate the mechanism of BPV-2 oncogenesis in bladder cancer. 

Method 

To analyse the amino acid sequences of bovine and human papillomaviruses and 

compare them to various oncogenes, especially mdm2, which binds to the tumor 

suppressor p53, and is overexpressed in some bladder cancers (Lianes P., 1994). 

Results: 

BPV-5 E6 PKD VLGR G CYYC 

Mdm 2 RL DEKQQHIVY PKN IVHGKT -GHL-MACFT- 

CAKKLKK 

BPV-2 E6 KL NEKQRHVLY LLHGKSLDRLCIRCCYCGGKLTK 

BPV-1 E6 

T 

HPV- 14, 21, 20 E6 V GKS V CYTC K L 

The motif GKT or GKS is an ATPase motif which binds phosphate PO4. In mdm2, the 

sequence KKLKK is a nuclear localizing signal. 

Conclusion 

Bladder cancer may be of viral origin, because bovine papillomavirus type 2 represent an 

experimental model (Campo M.S.) very similar to human disease. We found that BPV-2 

E6 oncogene is homologous to mdm2 oncogene, overexpressed in some bladder 

cancers. Thus it would be interesting to research more systematically papillomaviruses in 

human bladder cancer, particularly those which are metastatic. 


PP 3.1 

The Presence of HIV/AIDS in an Older Adult Population 

Bonnie F. Hatchet PhD ACSW 

Gerontology Institute University of Louisiana at Monroe Monroe, Louisiana Uniteds States 

The HIV/AIDS epidemic does not discriminate and there has been increasing focus on this 

important issue. There have been thousands of newspaper articles, hundreds of books 

and journal articles yet until the last five years there has been relatively little focus on older 

adults. A 1998 review of J of Gerontological Nursing found only 54 publications and two 

books discussing older adults living with AIDS. Since that time (1998) several books have 

been published and three journals have been devoted to the topic of HIV and older adults 

Research on Aging (Nov 1998); Journal of AIDS (June 2003) and AIDS (Jan 2004). 

They consist normally of case studies and secondary analyses of specific groups of older 

adults. According to Dr Issac Montoya an AIDS researcher in Houston few programs 

target older adults. 

Although fewer people are being diagnosed with AIDS (due to the success of HAART 

instead of changes in behavioral changes) the number of older adults living with AIDS is 

larger than ever. Between 1991 and 1996 the number of new cases of AIDS diagnoses 

rose twice as fast in people over 50 than those younger than 50 and although the rate 

slowed from 1996 to 2000, the increase in the older population continued despite great 

improvements in treatment for HIV that begun to be widely used beginning in 1996-1997. 

Some states do not include HIV in their reporting and in those that do there may be 

underreporting. The designation of 50 is used because the CDC uses that as the 

designation for older adults. Highly Active Antiretroviral Therapy (HAART) has extended 

the life of individuals living with AIDS. Ten percent of new AIDS cases are among 

individuals 50 and above. According to a recent study by the CDC (Centers for disease 

Control and Prevention) there were over 78,000 people age 50 and above living with AIDS 

in the United States. Because many older people do not get tested for HIV/AIDS on a 

regular basis there may be even more cases than we know. This poster presentation is 

based on interviews with older African Americans who are HIV positive or who are living 

with AIDS and focuses on emotional issues encountered and perceptions of ageism as it 

affects their care. 

POSTERS 


PP 3.2 

Is Age a Complicating Factor for Patients with Persistent Low Level Viremia? 

Boly L,Cafaro V, Dyner T 

Shared Perspectives on Therapies, San Francisco, United States 

Objectives 

Antiretroviral (ARV) regimens have become simplified with once daily dosing and 

decreased pill count. Side effects do persist for some patients and adherence remains a 

complicated issue. Continuing viral replication is thought to impact future treatment 

options and immunologic competence. Many patients decide to remain on their stable 

ARV treatment regimen despite the presence of low level viremia. While it has been 

documented that length of time on ARVs as well as nadir CD4 counts may influence side 

effects, chronological age may also contribute. We evaluated a group of patients with low 

level viremia and good adherence to their ARV regimens for any impact of chronological 

age on the experience of adverse side effects. 

Methods 

A retrospective chart review was conducted of 24 patients on stable ARV treatment 

regimens who had persistent low level viremia (HIV bDNA levels

PP 3.3 

Opportunistic infections associated to a late, first diagnosis of AIDS. Paradoxical 

increase of frequency at the time of highly active antiretroviral therapy (HAART) 



Introduction 

Notwithstanding the availability of HAART, AIDS notifications continue to occur, with 

increasing prevalence for patients (p) who missed or neglected their condition. 

Patients and Methods 

All cases of AIDS notified since the year 2001 were compared with those found in the 

decade preceding HAART availability (1986-1995). 

Results 

Compared with the pre-HAART era, a significant drop of frequency of overall AIDS cases 

occurred: from a mean 58.3±11.2 patients-year observed in the decade 1986-1995, to 

14.2±6.0 patients-year from 2001 to 2005 (p

PP 3.4 

Reversible HIV associated encephalomyelitis successfully treated with HAART 

Imbert P, Rapp c, Bladé JS, De Greslan T*, Barruet R , Flocard F*, Debord T 

Department of infectious and tropical diseases Military hospital Bégin,94163 Saint-Mandé, 

France * Department of Neurology Military Hospital Vâl de Grace,75006 Paris, France 

HIV is rarely associated to a demyelinating lesion of the central nervous system. We 

report a reversible HIV Associated Encephalomyelitis (HAREM) observation with a 

favourable outcome under HAART. 

Observation 

A 31 year old male is followed-up since 1992 for an asymptomatic HIV-1 infection (CD4 > 

500/mm 3 ). In February 2001, he presented with a severe retrobulbar optic neuritis and 

neurological impairments which evolved by episodes with an extended demyelination on 

the MRI. Rapid intravenous administrations of corticosteroids were ineffective. In June 

2002, an AZT-3TC-Efavirenz tritherapy was started, after noticing a viral replication in the 

CSF (600 copies/mL). A genotypic study of the resistances was done before the 

introduction of the treatment. Despite clinical effectiveness and excellent immunological 

and virological responses, the treatment was replaced in January 2003 by the AZT-3TCindinavir-ritonavir 

association following an acute episode of anxiety which made him 

attack his wife with a knife.The neurological improvement is currently continuing (sport 

and work resumption) and the MRI anomalies are progressively regressing. 

Comments 

In our patient, HIV encephalitis and progressive multifocal leucoencephalopathy (PMLE) 

were easily ruled out. Multiple sclerosis or acute disseminated encephalomyelitis (ADEM) 

were evoked, but corticosteroids were ineffective. HAREM is a rare demyelinating 

affection, associated to an in situ HIV replication that is responsible of inflammatory or 

vascular lesions of debatable mechanism. The clinical and radiological improvement 

under antiretroviral tritherapy pleads for this latter hypothesis and for an active treatment 

on the HIV replication in the encephalic sanctuary. 


PP 3.5 

Clinical and Bacteriological features of AIDS-Related Mycobacterium KANSASII 

and Mycobacterium XENOPI Infection: A Thirteen-Year Follow-up 



Introduction 

A prompt and effective diagnosis and a timely treatment of atypical mycobacteriosis and 

especially Mycobacterium kansasii and Mycobacterium xenopi disease, remains a serious 

challenge for clinicians engaged in the management of the immunocompromised host, 

including HIV disease. 

Patients and methods 

Fifteen and eight HIV-infected patients with a microbiologically-confirmed M. kansasii and 

M. xenopi respiratory infection respectively, have been observed in a 13-year period, out 

of over 3,700 hospitalizations performed because of HIV-associated disorders. 

Results 

These episodes were carefully evaluated from an epidemiological, bacteriological, clinical, 

and therapeutic point of view. In 10 out of 23 cases (43.5%) a bacteremia was also 

retrieved. The proportionally reduced crude frequency of atypical mycobacteriosis as 

HIV-related complication, which virtually disappeared after introduction of potent 

antiretroviral combinations (HAART) in 1996, is underlined. In early nineties, the lack of 

effective antiretroviral regimens made frequent the association of this opportunism with 

full-blown AIDS, a mean CD4+ lymphocyte count of nearly 20 cells/µL, and an extremely 

variable chest X-ray features. The recent detection of two further episodes was due to a 

late recognition of a far advanced HIV disease (so-called "AIDS presenters"), complicated 

by multiple opportunistic disorders. 

Conclusions 

M. kansasii and M. xenopi respiratory and/or disseminated infection continues to occur, 

and pose relevant diagnostic problems, including late or missed identification due to slow 

culture and frequently concurrent opportunistic disease. Serious therapeutic difficulties, 

due to the unpredictable in vitro antimicrobial susceptibility profile of these organisms, and 

the need to start as soon as possible an effective combination therapy which should not 

interfere with other medications (especially HAART), are also discussed. 

POSTERS 


PP 3.6 

Mycobacterium Ulcerans Cutaneous Infection (BURULI ULCER) : An Emerging 

Cause of Immune restoration Inflammatory Syndrom in Arican HIV-Infected Patients 

Rapp C, Ficko C, Imbert P, Barruet R, Debord T 

Department of Infectious and Tropical diseases, Military Hospital Bégin, Saint-Mandé 

94163 France 

The incidence of atypical mycobacteria-related Immune Restoration Inflammatory 

yndrome (IRIS) is underestimated in countries where the use of HAART is recent. We 

report a Buruli ulcer (BU) observation in a woman being treated for HIV-1. 

In August 2005, a 24 year old Ivorian woman, followed-up since 2004 for a HIV-1 

infection, presented with painless skin ulcerations of the left upper limb, which appeared 

one month after the introduction of HAART (Triomune ® ). The examination revealed 3 

painless skin ulcerations of the left upper limb, located in an area that was successfully 

treated for a probable Buruli ulcer in 2004 with a surgical excision followed with a skin 

graft. The Acid-Fast Stain of the skin biopsy was negative. The histological analysis 

showed an inflammation and a necrosis of the subcutaneous tissue compatible with a BU 

relapse. The CD4 count was 156/mm3 (37/mm 3 at the treatment introduction), the HIV 

viral load was not available. Humerus and chest radiographies were normal. The HAART 

was pursued and the lesions cicatrized in 8 weeks with local nursing. No relapse was 

observed after a 6 month period. 

In Ivory Coast, cutaneous infections due to M. ulcerans constitute an emerging disease 

on its way to supplant leprosy. HIV infection is not an established risk factor of the 

disease. In regions where the prevalence of both infections is high, the risk of relapse or 

of revelation of M ulcerans latent infections, due to immunity restoration, deserves to be 

known. The screening of nodular lesions must precede HAART introduction. Reinforced 

skin surveillance is necessary in the following months after treatment's initiation. 


PP 3.7 

Functional limitation of Mycobacterium ulcerans cutaneous infections (Buruli 

ulcer): usefulness of a functional limitation score 

Rapp C,Ficko C, Imbert P, Barruet R, Debord T 

Department of infectious and tropical diseases Military Hospital Bégin 69 avenue de Paris, 

94163 Saint-Mandé, France 

Buruli ulcer disease, caused by Mycobacterium ulcerans, is emerging in West Africa. Their 

low case fatality rate is contrasting with the significant morbidity and the growing 

ocio-economic impact of the osteoarticular sequelae. 

Objective 

To describe and quantify the functional sequelae of M ulcerans cutaneous infections in 

Ivory Coast. 

Patients and methods: All children over 2 years old and adults presenting with a Buruli 

ulcer (BU) and treated since 2003 for more than 3 months were included in a 3 month 

period. The functional damage was evaluated with a simplified quantitative score (a 

questionnaire of 15 items adapted to daily life activities) inspired from the Buruli ulcer 

functional score validated in Ghana by Stienstra an al (Am J Trop Med Hyg 2004). 

Results 

186 patients (96 males, 90 females) with a mean age of 16.5 years (3-72) were included. 

The distribution of the 230 observed lesions was: upper limbs (42%), lower limbs (52%), 

trunk and face (6%). The sequelae rate was 36.6% (n=68) with a mean functional 

handicap score of 18.6% (0-80). The amputation rate was 4%. The worst affected were 

children (23.4 vs 13.3%).The functional incapability of the patients resulted in 30% of the 

children being taken out of the school system and 40% of the adults losing their job. 

Comments 

Our results confirm the significance of sequelae and their impact on precarious and rural 

populations. The quantitative functional score is a simple and reliable tool. Its distribution 

in health care centers should allow the measuring of individual benefit of physiotherapy. 

On the community level, it can be used to evaluate necessary resources and to compare 

the effectiveness of the therapeutic interventions. The search for sequelae risk factors and 

appropriate management are urgent. 

POSTERS 


PP 3.8 

A Clinical Study Of 60 Patients Of Multidrug Resistant Tuberculosis in Mumbai, 

India 

Dr. Mohammad Khalid, Dr.Ganesh Rathod, Dr.Preeti Meshram. 

Senior Resident,Resident,and Lecturer respectively.Mumbai,India. 

Objectives 

Tuberculosis is disease with a history as long as that of mankind. 

In India 1/3rd of the population is infected with M. tuberculosis. Approximately 10% of the 

infected population suffer from tuberculosis over 30-40 yrs. According to the Drug 

Resistance Surveillance Programme conducted by WHO and IUATLD in 1995 the 

prevalence of MDR - TB in India was 13-14 %. 

Keeping the increasing trends of treatment failure cases in mind the study was conducted 

at J.J.Hospital & Grant Medical College with the following objectives: 

A. To study the clinical profile of presentation of MDR-TB 

B. To study the resistance pattern and sputum conversion rate of MDR-TB. 

C. To assess the bacteriological and radiological response to treatment. 

METHODS 

The Study was conducted from September 2003 to September 2005 

I) All cases were resistant to Isoniazid & Rifampicin. 

II) Detailed history was recorded 

III) Patients were investigated with 

a) Complete hemogram 

b) Chest X ray 

c) Sputum for AFB culture & Drug resistance testing 

d) HIV 

IV) Patients registered as MDR- TB were started on IInd line chemotherapy as per WHO 

V) Follow up of patients was done every month for six months initially and then every three 

months for sputum AFB microscopy and chest X-ray. 

AFB culture was advised after nine months of treatment with IInd line drugs. 

RESULTS 

DISTRIBUTION OF MDR TB CASES 

Pulmonary Extra Pulmonary 

57 3 

AGE WISE DISTRIBUTION 

Age in years No of resistant cases Percentage 

15-25 17 28.33 

26-40 31 51.66 

41-60 11 18.33 

61-70 01 1.66 

PATTERN OF RESISTANCE 

SHREZ HREZ SHRE SHRZ HRE HRZ SHR HR 

16 5 5 11 4 8 5 6 

Percentage of resistance to individual drug 


H R S E Z 

60 60 31 24 10 

(100%) (100%) (51.6%) (40%) (16%) 

RADIOLOGICAL PRESENTATION 

XRAY PULMONARY EXTRA PULMONARY 

NORMAL 3 

MINIMAL 11 

LESION 

MODERATE 10 

LESION 36 

FAR ADVANCED 

LESION 

TOTAL 57 3 

MORTALITY DURING TREATMENT 

SEX PULMONARY EXTRA PULMONARY 

MALE 

FEMALE 3 

TOTAL 3 

To Summarize the above Results 

1)The most common set of clinical features included cough,fever, dyspnoea and weight 

loss. 

2)The microbiological pattern of drug resistance was Isoniazid (n=60), Rifampicin (n=60), 

Streptomycin (n=31), Ethambutol (n=24), Pyrazinamide (n=10), 

3)The cases were followed up for 2 years. 

4)3 cases died during the course of treatment 

5)Sputum conversion rate at the end of 3 months was 21 (38.1%), at end of 6 months 37 

(67.2%), and at 9 months was 31 (68.8%). 

6)Nutrition and compliance was the key to recovery. 

POSTERS 

Conclusion 

1) The Increase in the frequency of infection with M.tuberculosis resistant to anti-TB 

drugs is a major threat to its treatment and control program 

2) The worsening situation can be effectively tackled by implementing the DOTS 

Plus programme with microbiological, psychosocial and nutritional support 

systems 

3) Regimen of IInd line drugs according to WHO guidelines must be administered 

for at least 2 years 

4) Proper treatment of associated comorbidities is important in the prevention of 

morbidity and mortality associated with MDR-TB. 


PP 3.9 

HIV and Tuberculosis: Partners in Crime 

Janak K Maniar *, Ratnakar R Kamath**, Sundhiya Mandalia***, Alok Maniar**** 

* Department of Infectious Diseases, Jaslok Hospital & Research Centre, Mumbai, India 

** Grant Medical College , Mumbai, India 

*** Department of Medicine, Imperial College London, UK 

**** Dr. Maniar's ID clinic, Mumbai, India. 

Background 

Tuberculosis is the commonest infection detected in HIV-infected individuals worldwide. 

Aim 

The aim of this study is to describe the clinical, bacteriologic and radiologic spectrum of 

tuberculosis (TB) in the setting of human immunodeficiency virus (HIV) infection in a 

tertiary care centre in Mumbai. 

Methods 

8640 HIV-infected individuals were screened for tuberculosis routinely from January 1998 

to December 2003, using clinical examination, chest X-ray and abdominal 

ultrasonography, sputum smears for acid-fast bacilli (AFB) and culture on 

Lowenstein-Jensen medium. 

Results 

TB was detected in 8078 (93.5%) patients of whom 3393 (42%) had pulmonary, 3514 

(43.5%) had extrapulmonary TB and 1171 (14.5%) had disseminated disease. 1238 

patients (36.5%) showed AFB in sputum, while 1154 (34%) showed growth on culture 

medium. 4174 had radiographic involvement. 781 (67%) individuals with disseminated 

disease had concurrent pulmonary involvement. All 8078 coinfected patients were treated 

with anti-TB therapy (ATT), of whom 6422 patients (79.5%) showed one or more adverse 

events. Gastritis was the commonest complaint followed by hepatitis and skin rashes. ATT 

resistance was detected in 482 individuals. 

Conclusions 

Tuberculosis is the commonest opportunistic infection in HIV positive patients in India, 

showing a higher prevalence of extrapulmonary and disseminated TB and adverse events 

due to ATT. Early recognition of concurrent OIs and their adequate treatment and 

prophylaxis is essential 


PP 3.10 

Mycological Findings From HIV-Positive Children and Adults in Nairobi, kenia 

Mashedi O.M M 1 ,. Bii.C.C 2 , Amukoye E. 1 , Kumon.K. 3 , Mwangi I 1 , Mohamed A 2 ., Ouko.T.T 2 , 

Njoroge N.W. 1 , Wambua M 2 , Mwangi.P 3 . Obanda A.P. 2 , Muita L 1 , Ukon.T 3 , Kanamoto 3 . 

1 

Center for Respiratory Research Disease, KEMRI. 2 Center for Microbiology Research, 

KEMRI. 3 Japan International Cooperation Agency (JICA). 

Corresponding author: Ms Olga Mashedi Email:omukasia@yahoo.com 

Introduction 

HIV/AIDS infection leads to an increase in opportunistic infections. Among these infections 

some are mycological. Candida albicans, is usually a normal flora, but it is emerging as 

an opportunistic pathogen. The objective of this study was to determine the fungal 

diversity in various specimens from children and adults infected with HIV in Nairobi, 

Kenya. 

Materials and Methods 

Mycological investigations were carried out on various specimens from HIV/AIDS infected 

children in an orphanage and adults in Mbagathi District Hospital, Nairobi. 120 specimens 

(swabs, blood, urine, sputum, saliva, high vaginal swabs, bronchiole alveolar lavage and 

skin scrapings were processed using standard procedures. 

Results 

Isolated included fungi, C.albicans (70%), C.glabrata (50%), C.parapsilosis and C.tropicalis 

(40%), Moulds such as Aspergillus versicolor, Trichophyton schoenleinii, Fusarium 

semitectum, Bipolari hawaiiensis (from blood) and Malassezia furfur were also isolated 

Conclusion 

From the various specimens, incidence of C.albicans in children was relatively higher than 

that in adults.C.glabrata, C.parapsilosis, C.Tropicalis isolated in this study have 

previously been documented to have high virulence leading to severity associated with 

these infections. Moulds such as, Aspergillus versicolor, Trichophytonschoenleinii 

Fusarium semitctum Bipolari hawaiiensis(from blood) and Malassezia fur fur most of 

which were isolated in children. The reason for this is yet to be delineated. The results 

indicate a need for further studies to better understand of these emerging opportunistic 

infections for easier management. 

POSTERS 


PP 3.11 

Clinicopathological comparison of Tuberculous and Cryptococcal meningitis 

presenting to a tertiary care hospital in Pakistan 

Rahmat Ali, Afrasyab Khan, Bushra Jamil, Arshad Iqbal, Saad Ali. 

1) Dr. Rahmat Ali The Aga Khan University, Medical College, Department of B&BS Karachi 

Pakistan 2) Afrasyab Khan. Medical Student Class of 2007 The Aga Khan University, 

Medical College, Male Hostel Room No. 211 Karachi Pakistan 3) Dr. Bushra Jamil. 

Assistant Professor Department of Pathology and Microbiology Aga Khan University 

Stadium Road, P.O. BOX 3500 Karachi 74800, Pakistan 4) Arshad Iqbal. Medical Student 

Class of 2009 The Aga Khan University, Medical College, Male Hostel Room No. 134 

Karachi Pakistan 5)Dr. Saad Ali Medical Student Class of 2009 The Aga Khan University, 

Medical College, Male Hostel Karachi Pakistan 

Objectives 

Tuberculous meningitis (TBM) and cryptococcal meningitis (CCM) are two common types 

of chronic meningitis. It is very difficult to differentiate TBM (seen in immunocompetent 

individuals) from cryptococcal meningitis. In the current study we tried to address 

Clinicopathological comparison of Tuberculous and Cryptococcal meningitis presenting to 

a tertiary care hospital in Pakistan. 

Methods 

The data were collected, retrospectively from the medical records of the patients who 

presented to AKUH with tuberculous (n=16) and cryptococcal (n=11) meningitis during a 

10 year period from 1995 to 2005. The signs and symptoms, laboratory findings and other 

variables were compared. None of the patients with TBM were HIV positive while four 

patients with CCM had AIDS. 

Results 

The common initial signs and symptoms in patients with TBM were fever (81.3%), altered 

mental status (68.8%) and headache (62.5%) and in patients with CCM were fever 

(90.9%), headache (72.7%) and cough (54.5%). The mean CSF values for the patient with 

TBM and CCM were: WBCs count: 228/mm 3 and 529.54 mm 3 , RBCs: 2010.75/mm 3 and 

178.54/ mm 3 , glucose: 52.33 mg/dL and 32.63mg/dL, protein: 289.48mg/dl and 

432.18mg/dL respectively. Three patients with TBM were determined to be in clinical stage 

1, 11 in stage 2 and 2 in stage 3 of the MRC criteria. The mean CSF glucose level 

decreased according to the stage in TBM. Four patients with CCM were in clinical stage 

1, 4 in stage 2 and 3 in stage 3. Patients with TBM were started on anti tuberculous 

therapy and all responded well to treatment. Two patients with CCM expired during 

hospital stay while the rest responded well to amphotericin B and were discharged on 

fluconazole. 

Conclusion 

It is not possible to differentiate TBM (seen in immunocompetent individuals) from 

cryptococcal meningitis (seen predominantly in immunocompromised individuals) on 

clinical grounds alone. Since CSF DR findings in the 2 conditions are similar, a high index 

of suspicion is necessary for early diagnosis of cryptococcal meningitis, which is not a rare 

infection. Cryptococcal antigen test and fungal cultures should be requested in all patients 

with CSF findings of low glucose, high protein, and moderately high WBC and RBC 

counts. 


PP 3.12 

Tuberculous meningitis in HIV-infected patients of the province of Castellon, Spain 

Nuria Tornador, Bernardino Roca 

Hospital General of Castellon, University of Valencia, Spain 

Objective: To describe the clinical presentation and outcome of tuberculous meningitis 

(TM) in patients with HIV infection of the province of Castellon, Spain. 

Methods 

All cases of TM attended at the five hospitals of the province of Castellon, from January 

1994 to December 2005, were studied. Cases were recovered with the help of the 

electronic databases of the Admission and Microbiology departments of every hospital. 

Descriptive statistics were used to report results, and Mann-Whitney U test was used to 

compare continuous variables in patients who died or not. 

Results 

A total of 15 cases, which belonged to 15 patients, were included. Median of age was 30 

years, with interquartile range (IQR): 29-39; 13 (87 %) were male; and 11 (73 %) were 

drug users. Four patients (27 %) had presented tuberculosis in other locations previously, 

and 2 (13 %) suffered TM and pulmonary tuberculosis at the same time. The most 

common presenting symptoms were fever in 14 patients (93 %) and headache in 12 (80 

%). Symptoms were present a median of 14 days (IQR: 8-25) and patients were 

hospitalized a median of 5 days (IQR: 3-14), before the diagnosis of TM was established. 

Nuchal rigidity was absent in 6 patients (40 %), the level of consciousness was diminished 

in 10 (67 %), focal neurologic deficits occurred in 4 (27 %) and the syndrome of 

inappropriate antidiuretic hormone secretion (SIADH) appeared in 6 (40 %). Computed 

tomography or magnetic resonance imaging of the brain were carried out in 10 patients 

(67 %) and detected abnormalities in 8 of those 10 (80 %). Chest radiographs were 

carried out in all patients (100 %) and showed lung infiltrated in 5 (33 %). Blood analysis 

disclosed hipoalbuminemia in 10 patients (67 %), increased alanine aminotransferase in 

5 (33 %) and decreased hemoglobin level in 14 (93 %); median of CD4 cell count was 112 

per mm3 (IQR: 44-129), only 2 patients had a CD4 count over 200 cells per mm3; median 

of log10 of HIV RNA was 3.9 (IQR: 3.2-5.8). Cerebrospinal fluid (CSF) analysis showed 

the following results, median (and IQR): glucose 23 (17-32) mg/dl, protein 142 (80-253) 

mg/dl, white blood cells 198 (62-269) per mm3, mononuclears were the predominant cells 

in 11 (73 %). Mycobacterium tuberculosis grew in CSF in 12 patients (80 %). Treatment 

was instituted with four antituberculous drugs in 12 patients (80 %) and with three drugs 

in 3 (20 %), 8 patients (53 %) also received dexamethasone. The median of 

hospitalization was 24 days (IQR: 13-56). Seven patients (47 %) died during 

hospitalization, 2 (13 %) presented sequelae 6 months later, and 6 completely recovered. 

In patients who died, CD4 cell count was lower (P = 0.021) and log10 of HIV RNA was 

higher (P = 0.049) than in those who survived. 

POSTERS 

Conclusion 

Most cases of TM in the province of Castellon occurred in patients with advanced HIV 

infection. Outcome was worse in patients with severe immunodeficiency or with poor 

control of HIV disease. 


PP 3.13 

Crohn's disease onset in a HIV/HCV co-infected woman taking pegylated interferon 

plus ribavirin 

Marco Bongiovanni1, Roberto Ranieri1, Stefano Ferrero2, Francesca Casanova3, 

Antonella d'Arminio Monforte1 

1Clinic of Infectious Diseases, S. Paolo Hospital, University of Milan, Italy; 2Pathology 

Unit, S. Paolo Hospital, University of Milan, Italy; 3Unit of Internal Medicine, S. Paolo 

Hospital, University of Milan, Italy 

Background 

The combination of pegylated interferon (Peg-IFN) and ribavirin is the optimal option to 

treat HCV-infection in subjects with or without HIV co-infection. Despite a clear correlation 

between Crohn's disease and HCV-infection, only few cases of Crohn's disease have 

been reported in HIV-infected subjects. 

Case report 

We report the case of a woman co-infected with HCV (genotype 3a) and HIV due to 

heterosexual intercourses. In October 2005, the patient was still naïve for antiretroviral 

treatment because of good immuno-virological parameters (CD4: 517 cells/mm 3 ; 

HIV-RNA: 390 copies/mL), but she had a quite advanced HCV disease (liver biopsy: 

ISHAK score 10; fibrosis index 2), so that a treatment with Peg-IFN (180 mcg/weekly) plus 

ribavirin (800 mg/daily) was initiated. HCV-RNA was 980000 copies/mL, AST 107 UI/L and 

ALT 68 UI/L; an abdomen ultrasound showed hepatic steatosis. HCV-RNA became 

undetectable and hepatic enzymes normalized after one month of treatment. Three 

months later, the patient was admitted to our Clinic for fever, melena and abdominal pain. 

Blood test showed anemia (Haemoglobin: 10,2 g/dL) and elevation of C-reactive protein 

(90 mg/dl, normal value < 5); CD4 cells decreased to 275 cells/mm3 and HIV-RNA was 

undetectable. The physical examination revealed a mild abdominal pain and a body 

temperature of 39° C. Abdomen radiography and ultrasound were negative as were blood 

and stool examinations. Endovenous treatment with ciprofloxacin and metronidazole was 

started. A colonoscopy showed an inflammatory feature with aftous reactions and 

necrotic areas 60 centimetres far from anus. The histological examination showed 

erosions of the epithelial mucosa with marked acute and chronic inflammation with 

muscolaris mucosae involvement suggesting an inflammatory bowel disease. Mesalazine 

(800 mg 4 times daily) was started followed by a rapid clinical recovery. Peg-IFN and 

ribavirin were continued because of the early virological response and the recovered 

clinical conditions. 

Conclusions 

Crohn's disease seems to have an immune pathogenesis. The onset of this event in HIV 

subjects usually occurs in patients with high CD4. An association between interferon 

therapy and onset of Crohn's disease has been described in HCV mono-infected subjects. 

At our knowledge, this is the first report describing the onset of Crohn's disease in a 

HCV/HIV-infected subjects taking Peg-IFN plus ribavirin. This event does not seem 

associated with HIV-infection for the decrease of CD4 and for the good virological control. 

The role of HCV-infection is also opinable for the early virological response to anti-HCV 

therapy. Finally, the symptoms of Crohn's disease occurred three months after Peg-IFN 

plus ribavirin were started, probably a too short period to determine immune modifications. 


PP 3.14 

HIV-Associated Fungal Opportunism in the HAART Era. Trend of Frequency, 

According to Protease Inhibitor Administration 



Introduction 

Ten years after the introduction of highly active antiretroviral therapy (HAART), 

opportunistic AIDS-related fungal infections show a progressive drop of incidence. Aim of 

our work is to assess the temporal trend of major AIDS-associated fungal infections during 

the last four-year period, and to relate our figures with HAART administration, and the 

different combinations of administered antiretrovirals, with attention focused on protease 

inhibitors (PI). 


Through a retrospective analysis of clinical-microbiological records, 119 episodes of AIDSdefining 

visceral mycoses were identified from the year 2001 to 2005. 

Results 

The great majority of the 119 episodes of visceral mycosis was represented by 

esophageal candidiasis (99 cases), followed by CNS and/or disseminated cryptococcosis 

(19 episodes),and candidemia (1 case). The temporal trend demonstrated a progressive 

tendency to a reduction of diagnosed cases: 34 in the year 2001, 27 in 2002, 25 in 2003, 

19 in 2004, and 14 in the year 2005. In even 63 patients (p) of 119 (52.9%), visceral 

mycoses occurred concomitantly with the first positive HIV serodiagnosis: the so-called 

"AIDS presenters", who were never treated with antiretrovirals. In the remaining 56 

episodes, fungal infections occured as the first AIDS-related disorder in 30 cases, while in 

26 p they represented a subsequent opportunistic complication interesting p already 

diagnosed with AIDS. Although all p suffered from an advanced HIV disease (as 

expressed by a CD4+ lymphocyte count of 126.2±48.9 cells/µL), among the 58 patients 

taking antiretrovirals, PI were administered in 13 p only, while other combinations 

excluding PI were used in 45 p (p

PP 3.15 

Ocular manifestations occurred in decline of HAART, concerning 4 observations 

Eholié S*, Tanon A*, Say T*, Fany A**, Bissagnéné E*. 

* Infectious disease department, CHU Treichville, Abidjan, Ivory Coast ** Ophtalmologic 

department, CHU Treichville, Abidjan, Ivory Coast. 

Objective 

This study intended to bring back observations of ocular manifestations occurred in decline 

of the anti retroviral treatment and to realise the review of the literature. 

Observations 

Four observations concerned one man and three women aged respectively 22, 24, 27 and 

60 years. On the introduction of antiretroviral treatment, three patients were at stage C3 

(CDC 1993) except the one of 24 years at stage B3. The respective nadir of CD4 

contained 4 cells/mm 3 (0,5% of T4), 15 cells/mm3 (2 % of T4), 85 cells/mm 3 (11 % of T4) 

and 189 cells/mm 3 (16 % of T4). Any functional ophthalmologic symptomatology of 

specific ocular antecedents was objectivized during the initial check-up. Any of the four 

patients entitled an ophthalmologic check-up before the anti retroviral treatment. Only one 

patient had risk factor type non insulin dependent diabetes. The period of ocular signs 

arrival was less than 3 months for 3 patients and one year to the 60 aged. In the four 

cases, an immunological recovery was noticed before ocular complications' diagnosis. 

Ophtalmologists diagnosed in three cases a retinitis and in one case an uvéite probably 

due to a CMV infection. Any biological confirmation could be done (antigenemia PP65, 

PCR, CMV viremia). The inflammatory reconstitution immune syndrom diagnosis was 

adopted in three cases. To 27 and 60 aged patients, we instituted the specific treatment 

of Cytomegalovirus based on ganciclovir, associated with a maintenance treatment 

intravenously during 2 weeks. The evolution showed the blindness to three of patients. 

Conclusion 

These observations caused a literature's review that revealed ophthalmologic 

manifestations in the decline of the anti retroviral treatment are rare but with bad 

prognosis when there is a delay in the diagnosis and the medical expenses fully paid. The 

inflammatory reconstitution immune syndrom should be recognized and different from 

events classifying AIDS (stage C). 


PP 3.16 

Neurophysiological and neurometabolic characteristics of patients under HAART 

with cognitive complaint. 

Frixon-Marin V*(1)., Poizot-Martin I.*, Drogoul M.P*, Michotey P.** Gastaut J.A*. 

and Vion-Dury J***. 

*CISIH, CHU Ste Marguerite, ** : Department of Radiology, Hôpital Ambroise Paré, *** 

Service de Neurophysiologie Clinique, CHU Conception ; Marseille France 

About 20-40% of HIV patients under HAART display cognitive troubles, affecting mainly 

memory and attention. Neurophysiological and neurochemical status have been 

evaluated in 35 patients (27 males and 8 females), presenting a cognitive complaint, using 

respectively: a) P300 cognitive evoked potentials (acoustic oddball paradigm) and 

standard EEG, and b) brain proton magnetic resonance imaging (MRI) and spectroscopy 

(MRS; PRESS sequence, TE 135 ms, TR 1500ms. NAA/Cho, NAA/Cr and Cho/Cr 

metabolic ratios analyzed.) At the time of examination, 22 patients presented an 

undetectable blood viral load, and 8 a viral load 400 = x =10000. 

Twenty patients (57%) display an abnormal EEG, mainly characterized by vascular signs 

abnormal for age (alpha waves diffusing in frontal areas, sharp slow waves….). EEG is 

always abnormal in the 8 patients with a low (< 200) blood CD4 count. 

Twelve patients (34%) display an abnormal P300 (increase in P3B latency for age). 

P300 is found significantly more frequently abnormal in patients with CD4 < 200, than in 

patients with CD4 > 200 (p = 0.05, chi2 test). 

MRI is normal in only 10 patients (29%). Non specific WM abnormalities and/or a atrophy 

(cortical or sub-cortical) are the most frequent abnormalities. 

MRS is abnormal (2 of 4 recorded spectra with one abnormal metabolic ratio) in 22 (62 %) 

patients. 

Cognitive troubles in HIV patients under HAART are accompanied by both 

neurophysiological and neurochemical significant abnormalities suggesting that they are 

clearly from an organic origin. The viral and/or iatrogenic cause of such abnormalities 

remains to be precised. Neurophysiology and MRI features are compatible with the 

hypothesis of a premature ageing. 

POSTERS 


PP 3.17 

Bladder carcinoma observed in HIV-infected patients. An infrequent, 

but challenging finding 

Roberto Manfredi, Sergio Sabbatani, Leonardo Calza 


Introduction 

The majority of AIDS-related malignancies declined after HAART introduction. The 

notification system reports AIDS-linked disorders only upon diagnosis, while pathologies 

occurring in patients (p) already diagnosed with AIDS are underestimated. Increasing 

cancer may be caused by the prolonged patient's life expectancy, the residual immune 

imbalance, and the late detection of HIV. Among solid tumors, bladder neoplasms are 

extremely infrequent, with only three anecdotal episodes reported to date. 


Since more confidence with HIV-cancer association is neded, we report three recent 

cases of relapsing HIV-associated bladder carcinoma. 

Results 

Our experience of three cases of transitional, papillary, stage G2 bladder carcinoma, had 

some common points: it interested male p in their fifth decade of life, specific risk factors 

were excluded, and HIV infection lasted from 2-4 years, and was fully controlled by 

HAART, from a virological-immunological point of view. While the single relapse of 

bladder carcinoma experienced by our first and second patient required endoscopic 

surgery and local chemotherapy, the multiple recurrences and the advancing disease (G3) 

stage led to a radical cystectomy in the third p, despite repeated endoscopic, surgical, and 

cytotoxic therapy, but cancer appeared under control in all our p during the subsequent 

8-18-month follow-up. The urologic support was valuable for early diagnosis and 

appropriate therapy and monitoring, which needed repeated endoscopical and surgical 

interventions, and intravesical chemotherapy, although only radical surgery proved 

effective in our third p. 

Conclusions 

Although the proportionally rare occurrence of HIV-associated bladder carcinoma and the 

lack of correlation with HIV disease progression could result in a trivial association, this 

neoplasm is burdened by an apparently increasing incidence. In fact, only three cases 

were presented as single reports, two of them in the pre-HAART era. Clinicians facing HIV 

p with frank hematuria should consider a bladder carcinoma, to avoid missed or delayed 

diagnosis and management. 


PP 3.18 

Important cutaneous reaction during enfuvirtide (Fuzeon ® ): an 8 cases report 

Brunet C¹, Ravaux I¹, Martin-Loï S¹, Lecomte-Suzan V¹, Mars-Kallee ME², Dignat-George 

F¹, Gallais H¹ 

1 

CHU La Conception, Marseille, France 2 Roche Pharma France 

Objective 

Enfuvirtide (Fuzeon ® ), the first HIV1 entry inhibitor is an injectable antiretroviral. Its main 

adverse event (AE) is generally a site reaction injection (SRI), but in rare cases this 

reaction can be important. The aim of this study was to describe clinical, haematological, 

virologic and immunologic characteristics of patients (pts) who experienced during 

Fuzeon ® injection an important cutaneous reaction (ICR) because of its extension or its 

dissemination. 

Method 

From May 2003 to September 2004, all HIV1 infected pts who started Fuzeon ® in La 

Conception Hospital (Marseille), were enrolled in a 12 month prospective cohort study. 

Clinical, virologic, immunologic and haematological exams were performed at day 0 and 

every 3 months. Patients who have presented an ICR were retrospectively studied. 

Results 

During this period, 45 pts have started Fuzeon ® in this unit. Thirty patients (67%) have 

presented a cutaneous reaction. It was a SRI in 49% of cases (22/45) and an ICR in 17% 

of cases (8/45). The majority (54%) of patients who have presented an ICR had a large 

past of drug allergies (toxidermia, urticaria or disseminated cutaneous eruption). This IRC 

occurred during the first month on therapy in 6/8 cases (75%). It was a toxidermia (in 2 

cases) or fever (38,5-39°C) with a very extensive, painful and pruriginous induration (in 6 

cases). Only 2/8 pts discontinued therapy. In all 6/8 others pts cutaneous reaction 

disappeared progressively. 

In 75% of cases during ICR we noted a peak in CD8 T lymphocytes (+1000 cells/mm 3 - 

median-) and in platelets (+50 G/L -median-). No other biological anomalies (in particular 

in IgE, haemoglobin, white or red blood cells and CD4 T cells count) were observed. 

In this cohort, only 15% of patients who have experimented a classical SRI had a past of 

drug allergy (p=0.01) and none have presented a peak in CD8 T cells count or in 

platelets. 

POSTERS 

Conclusion 

In our cohort important cutaneous reaction generally occurred in patients with a past of 

drug allergy. It was rare, transient, without durable biological consequence. In most of 

cases therapy can be continued. Nevertheless, larger prospective studies are needed to 

confirm these facts. 


PP 3.19 

Increasing concerns related to gynecomastia among HIV-infected patients treated 

with highly active antiretroviral therapy (HAART). Epidemiological and clinical 

correlates, and startpoints for pathogenetic investigation 



Introduction 

Gynecomastia (G) is an emerging untoward event in patients treated with HAART. 


Through a cross-sectional study performed on around 1,000 HIV-infected patients (p) 

treated with antiretrovirals at our reference centre in Bologna (Italy), we identified all cases 

of G related to the administration of at least 12 consecutive months of HAART, to assess 

possible correlations of G with a spectrum of clinical, laboratory, and therapeutic variables 

(and including all adverse effects of HAART itself). All p with true G (as distinguished from 

lipomastia by an ultrasonography assay) were considered evaluable, while p with other 

predisposing conditions (endocrine disease, alcohol abuse, liver cirrhosis, and use of drug 

possibly predisposing to G), were carefully ruled out. 

Results 

Twenty-one out of 616 evaluable HIV-infected male p (3.4% of our p population), 

developed a true G when aged 12-58 y. Seven p out of 21 never received protease 

inhibitor (PI)-containing therapies, while efavirenz-based regimens apparently prompted G 

in 7 p who were naïve for PI, and worsened this disturbance in three further p who 

abandoned PI for efavirenz. Considering nucleoside analogues (NA), two p developed G 

during treatment conducted with dual isolated NA. Comparing the different adminstered 

NA, stavudine seemed to be the most commonly used compound, also taken for the 

longest time (p

PP 3.20 

Renal function tests and blood electrolytes before and after atazanavir 

Bernardino Roca, Laura Alcon, Daniel Bahamonde, Nuria Tornador and Jose Manuel 

Ventura 

Hospital General of Castellon, University of Valencia, Spain 

Background 

Atazanavir seems to have fewer side effects than other protease inhibitors, although 

limited information exists in that field. We aimed to determine the possible occurrence of 

renal dysfunction and blood electrolyte abnormalities with the medication. 

Methods 

In a cohort of HIV infected patients, we assessed blood urea nitrogen, creatinine, sodium, 

potassium and chloride levels before and after changing to modalities of anti-HIV therapy 

than included atazanavir. We also evaluated HIV viral load and CD4 lymphocyte 

response to such therapy switch. 

Results 

A total of 60 patients were studied; all of them had received at least one modality of 

anti-HIV treatment previously. Mean (and standard deviation) of age was 37.5 (+/- 7.1) 

years; 37 (62 %) were male; 33 (55 %) had acquired HIV via drug use; 36 (60 %) were 

coinfected with hepatitis C virus. Three patients (5 %) stopped atazanavir therapy before 

completing 1 month of treatment: two of them because of jaundice and another one 

because of vomits. Blood analyses were available from all 60 patients; mean (and 

standard deviation) of results before and after atazanavir therapy institution (and 

significance level of difference, paired-samples t test) were as follows: urea nitrogren, 

mg/dl: 13.6 and 13.3 (P = .596); creatinine, mg/dl: .85 and .87 (P = .205); sodium, mEq/l: 

138 and 139 (P = .569); potassium, mEq/l: 4.3 and 4.3 (P = .822); chloride, mEq/l: 101 

and 101 (P = .129); HIV RNA, log10 copies/ml: 3.31 and 1.76 (P = .000); and CD4 

lymphocyte count, cells per mm3: 323 and 393 (P = .007). Urea nitrogen higher than 

normal range was present in 1 patient before atazanavir therapy and in 1 patient 

afterwards (P = 1) and creatinine higher than normal range was present in 0 patients 

before atazanavir therapy and in 2 patients afterwards (P = .5). 

POSTERS 

Conclusions 

Atazanavir seems to cause no relevant alteration in renal function tests and blood 

electrolytes. 


PP 3.21 

Glucose intolerance and insulin-resistance found in HIV-infected subjects during 

their anti-HIV protease inhibitor treatment: a prospective, randomized comparison 

study of three oral hypoglycemic drugs 

Leonardo Calza, Roberto Manfredi 


Introduction 

HAART-related dysmetabolic alterations recently emerged in their frequency and clinical 

correlates. When considering protease inhibitor (PI)-treated patients (p) a high 

prevalence (30-80%) of insulin-resistance and hyperinsulinemia have been found, versus 

a lower (

PP 3.22 

Multiple subcutaneous lipomatosis prospectically observed in patients receiving 

highly active antiretroviral therapy (HAART). Possible links with concurrent 

metabolic abnormalities, and pathogenetic insights 



Introduction 

As a consequence of the availability of highly active antiretroviral therapy (HAART), the 

lipodystrophy syndrome and a broad spectrum of metabolic abnormalities progressively 

emerged in the last decade (1997-2006). Localized fat accumulation may occur as 

visceral adipositiy, increased breast size, gynecomastia, lipomastia, and the so-called 

buffalo hump, although very limited reports are to date available on the role of 

lipomatosis during HIV infection. 

Patienys and Methods 

Nineteen patients (p) out of over 1,000 treated with HAART as of end of December, 2005 

(>1.5%) (15 males and four females, aged 36-58 years), experienced multiple 

ultrasonography-confirmed subcutaneous lipomas (three to over 20 lesions), 

predominantly involving the trunk and upper and lower limbs, usually associated with local 

discomfort. 

Results 

Among involved p, the duration of HIV seropositivity at lipomatosis onset varied between 

32-116 months, and no p had developed full-blown AIDS. Our 19 p experienced 5-14 

different anti-HIV therapeutic lines: almost all available protease inhibitors (PI) and 

nucleoside analogues had been used previously or during the occurrence of lipomatosis, 

while a NNRTI was used by in five p only. All p were given a PI-based HAART since 

16-74 months (mean 28.2±13.9 months). While the virological-immunological situation of 

HIV disease remained favorable, a broad spectrum of concurrent lipodistrophy 

syndrome- and dysmetabolic-related alterations were found. In detail, an evident 

lipoatrophy was present in 15 p out of 19, associated with central adiposity in 12 p. 

Hypertriglyceridemia, hypercholesterolemia, and hyperglycemia were detected at in 15, 

10, and three p, respectively. The subsequent follow-up (8-70 months), was characterized 

by the occurrence of further lesions in 10 p (with five p undergoing plastic surgery with 

satisfactory results), and a substantially stable disease in the remaining 9 p, in absence of 

spontaneous regression, even when the initial HAART regimen was changed. 

POSTERS 

Conclusions 

Sucutaneous lipomas have not been reported with increased frequency during HIV 

infection, including the HAART era. An accurate diagnostic workup (ultrasonography and 

eventually fine-needle biopsy) is needed to prevent the rare occurrence of malignant 

degeneration. The frequent association of lipomatosis with other clinical-metabolic 

disturbances related to HAART, should deserve further epidemiological and pathogenetic 

studies, to better investigate their eventual, mutual relationship, and to identify and plan 

eventual prevention strategies. 


PP 3.23 

Proviral DNA and plasma viral RNA resistance mutations in HIV1 naive patients 

B. Kabamba Mukadi1, A. Dusquenne 1 , J. Ruelle 1 , J-C. Yombi 2 , B. Vandercam 2 , 

M. Bodéus 1 , P. Goubau 1 . 

1 

Laboratoire de référence SIDA, 

2 

Centre de prise en charge, 

Université Catholique de Louvain, 

Avenue Hippocrate 10, 1200 Bruxelles, Belgium. 

Objectives 

HIV mutations associated with antiretroviral drug resistance may be carried by 

transmitted strains in therapy naive patients. At present, HIV-1 drug resistance mutations 

are detected by analysing plasma viral RNA. The HIV-1 proviral DNA could be an 

alternative marker, as it is known that proviral DNA persists in infected cells, even after 

prolonged successful HAART. 

Methods 

This is a prospective study of the prevalence of HIV-1 drug mutations in proviral DNA from 

purified CD4+ cells as compared to the plasma viral RNA in naive patients. The Forty tree 

selected naive patients had a mean viral load of 5.27 log (2.6 - 5.87) with a mean CD4 

lymphocyte value of 338/mm3 (6 - 1460). They include 58 % of Europeans and 42 % of 

non-Europeans, mostly people from central Africa. Sequenced HIV-1 viruses comprise 

39% and 61% of subtype B and non-B, respectively. Genotypic antiretroviral drug 

resistance mutations were determined by an in house RT- PCR method applied on RT and 

PR genes. Direct cycle sequencing was carried out on the ABI Prism 310 sequencer. In 

case of PCR failure, samples were analysed by Versant HIV-1 Resistant Kit. Identified 

mutations were those listed in the ARNS algorithm list (September 2005). 

Results 

Out of the 380 detected resistance mutations, 213 and 167 mutations were detected in 

CD4+ cells and in the plasma, respectively. Fifty five percent of PR mutations and 22,5% 

of RT mutations were simultaneously present in both CD4+ cells and plasma. The 

prevalence of patients with viruses carrying at least 3 secondary PR mutations was 86,2% 

and 74,4% in CD4+ cells and in the plasma, respectively. Forty percent of patients had at 

least 1 RT mutation in CD4+ cells while 33% had at least 1 RT resistance mutation in the 

plasma. The only detected proviral RT key mutations were M184V and M184I (5.3% of RT 

mutations) in different patients, but not found in the plasma. The final resistance mutations 

interpretation showed 93% of identical results in both CD4+ cells and plasma. One patient 

had a virus with RT resistant profile (67N, 70R, 219Q) in both CD4+ cells and plasma. 

Conclusion 

We cannot exclude the presence of minority resistant viruses as a consensus sequence 

was obtained and the sensitivity of sequencing to detect mixed populations is commonly 

estimated to be between 20 and 50%. Although wild-type virus may overgrow any initial 

resistant virus in patients with chronic asymptomatic HIV infection, a very low prevalence 

of key mutations was detected. The only frequent mutations detected were protease 

secondary mutations, which are less relevant for drug resistance. HIV1 proviral DNA 

resistance testing may be useful in chronically infected individuals or in patients with 

undectable viremia as more resistance mutations were detected in CD4+ cells. 


PP 3.24 

Elevated serum lactic acid levels during highly active antiretroviral therapy 

(HAART). Frequency, possible pathogenetic causes, and potential clinical 

significance 



Introduction 

Despite the increasing evidence of hyperlactatemia as an emerging side effect of HAART, 

its frequency, pathogenesis, management, outcome, and prevention are still under active 

investigation. 


A case-control study has been performed on over 1,000 HIV-infected patients (p) in the 

years 2004-2005. When evaluating HAART-treated p with adherence levels of at least 

90%, p with hyperlactacidemia were compared with p with normal lactate levels, in 

relation with a broad spectrum of variables. 

Results 

Of the 755 evaluable p, 272 (36%) experienced at least one evidence of hyperlactacidemia 

(mean value 24.7±8.8 mg/mL). Only 56 p of the study group (7.4%) experienced two 

or more subsequent alterations, with progressively increasing levels in 73.2% of p, while 

a grade 4 hyperlactatemia (>39.6 mg/dL) was found in five p only (0.7%). When 

comparing the 272 p with elevated lactacidemia with the 483 control subjects, no 

significant difference was seen as to age, gender, type of risk for HIV infection, duration 

and stage of HIV disease, CD4+ lymphocyte count, HIV plasma viral load, and type and 

duration of use of single and combined antiretroviral drugs (HAART). In an univariate 

analysis, p with hyperlactacidemia showed a significantly longer anti-HIV therapy 

(p

PP 3.25 

Frequency, monitoring, clinical significance, treatment, and prevention 

determinants of pancreatic toxicity in the era of highly active antiretroviral therapy 

(HAART) 



Introduction 

The epidemiological-clinical features of HIV-associated pancreatic anomalies are evolving 

significantly during HAART availability. 


The frequency, risk factors, and clinical-therapeutic features of pancreatic alterations were 

assessed in a case-control study. 

Results 

Around 1,000 HIV-infected patients (p) were assessed for pancreatic abnormalities during 

the whole follow-up period of each p. One hundred and 38 p found with high and/or 

prolonged laboratory anomalies were assessed with better detail, in order to outline the 

profile of pancreatic disease before and during the HAART era. Compared with control p, 

the 345 p (35.6%) who experienced at least one episode of pancreatic laboratory 

abnormality had a longer duration of seropositivity, protease inhibitor use, a more frequent 

immunodeficiency and AIDS diagnosis, concurrent liver-biliary disease, and 

hypertriglyceridemia. Among these 345 p, high and/or prolonged alterations eventually 

associated with signs of organ involvement occurred in 133 p, and were associated (with 

descending frequency) with the administration of didanosine, stavudine, a PI-based 

HAART (and the frequently related hypertriglyceridemia), and lamivudine, or with 

substance and/or alcohol abuse, opportunistic infections, liver-biliary disease, and (at a 

lower extent), with the use of combined anti-tubercular therapy, pentamidine, or 

cotrimoxazole. However, no difference was noticed between the 34 p with clinical and/or 

diagnostic imaging (ultrasonographic and/or CT) evidence of pancreatic involvement, and 

the remaining 99 asymptomatic p. Although recurrences of enzyme alterations involved 

over 70% of p, in only 33.8% of p a change of antiretroviral and/or antimicrobial therapy 

proved necessary. An acute but uncomplicated pancreatitis occurred in eight of the 34 

symptomatic p (23.5%). A 2-4-week gabexate mesylate and/or octreotide administration 

(performed in 48.1% of p), achieved a significant laboratory, clinical, and imaging cure or 

improvement in 71.9% of overall treated p, with a better success rate of combined versus 

single pharmacologic therapy. 

Conclusions 

Epidemiological and pathogenetical studies are strongly needed to assess the 

significance and the outcome of HIV-associated pancreatic abnormalities in the HAART 

era, considering that a broad spectrum of direct and indirect pancreatic toxicity may occur. 

Gabexate mesylate and/or octreotide indications strongly deserve controlled studies, also 

on a cost-effectiveness point of view. Finally, the frequent persistence of altered serum 

pancreatic enzymes is of frequent and relevant concern when re-starting or continuing 

antiretroviral therapy in this special p group. 


PP 3.26 

Invasive Candidiasis and Cryptococcosis Disclosed Concurrently in AIDS 

Presenters 



Introduction 

The introduction of highly active antiretroviral therapy (HAART) changed the natural 

history and course of HIV infection, first leading to a drop of opportunism related to a 

severe immunodeficiency, including visceral candidiasis-cryptococcosis. However, the 

incidence of the so-called "AIDS presenters" is increasing during HAART, since patients 

(p) who are unaware of or neglect their HIV disease, cannot take any advantage from 

HAART. 


Two rare case reports of concurrent visceral Candida-Cryptococcus co-infection occurred 

in p with a undiagnosed HIV disease, are presented. 

Results 

Two p who were unaware of their HIV disease, were referred to us with a far 

compromised clinical situation, including prolonged fever, dysphagia, pancytopenia and 

weight loss, Pneumocystis carinii-Mycobacterium kansasii-Staphylococcus aureus 

pneumonia in the first p, and persisting headache in the second p. A candidiasis was 

confirmed by esophageal biopsy in both cases, while the first p also had positive Candida 

albicans blood cultures. Cryptococcosis was the result of fungemia in the first p, and 

meningeal localization in the second p, whose CSF proved positive at both culture and 

polysaccharide antigen search. The severe immunodeficiency of our p was expressed by 

a CD4+ lymphocyte count of 44 and 13 cells/µL, respectively. After the diagnosis of 

concomitant dual Candida-Cryptococcus infection was made, fluconazole, and concurrent 

liposomal amphotericin B in the first patient, were administered, leading to mycological 

and clinical cure. No relapses of yeast opportunism occurred during the 24-56-month 

follow-up, while immune reconstitution took place thanks to HAART. 

POSTERS 

Conclusions 

Multiple, concomitant or subsequent AIDS-defining illnesses were anecdotally described, 

but the concurrent detection of two different visceral yeast diseases has no equivalents in 

the literature, to the best of our knowledge. Preventive-educational efforts are strongly 

needed for each population target, since many p are at risk of suffering from a missed or 

delayed HIV recognition, and have an increased risk of advanced, life-threatening HIV 

disease including multiple AIDS-related disorders. 


PP 3.27 

HIV-positive cases as part of viral complications after renal allotransplantation 

KT Metodiev¹, PG Lazarova², VI Driyanskaya³ 

1 

Dept.Immunology, Medical University, Varna-Bulgaria; 2 Clin.laboratory, District hospital 

"St.Anna", Varna-Bulgaria; 3-Lab.immunology, Inst.Urology&Nephrology, Kiev-Ukraine 

Background 

It is well-known that recipients of renal allografts suffer from two major complications after 

transplantation: rejection crisis and infections. The rejection process is a well-expressed 

immune conflict. The infectious processes have various etiology but most often are the 

viral ones, followed by bacterial and fungial. 

Objectives 

It is very essential that a proper, rapid and precise diagnosis, as well as a realistic 

prediction of the two postoperative complications, must be performed because they 

require rather different therapeutical behaviour. 

Materials and methods 

The authors of the present study examine dynamically 128 recipients of renal allografts 

(before and after transplantation, twice weekly during the first month postoperatively, twice 

monthly for the period of the first year) by using both, the immunologic monitoring (IM) and 

virologic methods (VM), trying to analyse the possibilities for diagnosis and prognosis of 

rejection and infections, also to investigate the etiology of viral processes. The IM includes 

basic immune tests for cellular, humoral, specific and nonspecific immunity, type of 

immunoreactivity and current immunomodulation, whereas the VM are directed to 

antibody and antigen identifiction, also HIV-serologically positive recipients and 

HIV-virocarriers (patients on haemodialysis before renal allotransplantation and patients 

after operation) by using ELISA. 

Results and conclusions 

Based on the results the authors suggest that the applied model of IM allow statistically 

reliable exact differentiation and prediction (!) of both complications (rejection and 

infections). As for the viral infections (altogether 58 for the whole group of 128 recipients), 

the following etiology is registered: hepatitis (21 cases or 36.2%), CMV (11 or 18.9%), 

Influenza (9 or 15.5%), Adenoviral (4 or 6.9%), ECHO (2 or 3.45%), HIV-serologically 

positive cases (3 or 5.2%), from them HIV-virocarriers (2 or 3.45), mixed viral infections 

(6 or 10.4%). The immunoreactivity type of the recipients shows that the lower the 

immune status is, the oftener are the infections, especially those with viral origin. 

Expressed immunodeficiency is registered in 7 cases (CMV-2, Influenza-1, mixed viral 

infection-1 and HIV-3). Detailed analysis of the therapy (antiinfective and 

immunosuppressive) for both posttransplantation complications is proposed. The model of 

IM allows a very reliable analysis and prediction of the immune conflict or infections in the 

postoperative periods, thus giving a precise idea for the exact therapy of allograft patients. 


PP 3.28 

Successful treatment of AIDS-associated Cryptococcus neoformans meningitis, 

apparently prompting the emergence of amphotericin B-resistant Cryptococcus 

laurentii central nervous system infection 

Roberto Manfredi 

Roberto Manfredi, Ciro Fulgaro 

Introduction 

Less than 20 episodes of Cryptococcus laurentii infection were described until now in the 

international literature. 

Case report 

A 34-year-old male with HIV infection since 8 years, was lost to follow-up until his hospital 

admission, due to severe fever and headache. A moderately advanced infection was 

shown by a CD4+ lymphocyte count of 151 cells/µL, and a viral load of 122,861 HIV-RNA 

copies/mL. Cerebrospinal fluid (CSF) culture and capsular antigen assays confirmed a 

Cryptococcus neoformans meningitis, with full susceptibility to all polyenes and azoles. 

Liposomal amphotericin B (lAB) was started at 3 mg/Kg/day with immediate benefit, but 

our p self-discharged after only 12 days, and denied further monitoring, until a subsequent 

hospitalization occurred 14 weeks after, owing to the same signs-symptoms. 

C. neoformans was isolated again from both CSF and blood, with positive antigen search 

in both CSF and serum, and a persisting sensitivity to all antifungals. Negative CSF-blood 

microscopy-cultures were achieved after 28 days of lAB administration associated with 

flucytosine. Six weeks after patient's discharge, a novel relapse occurred despite HAART 

initiation and a weekly maintenance with lAB. At that time, the CSF study disclosed an 

unexpected, isolated C. laurentiii, which proved resistant to both lAB and flucytosine, but 

sensitive to all azoles. Concurrently, all mycological searches for C. neoformans infection 

tested negative. High dose fluconazole started, and HAART continued:after 43 days, 

negative C. laurentii microscopic-culture CSF assays were obtained, and no further 

episodes of relapses of cryptococcosis occurred during the subsequent 65-month followup, 

also thanks to a restored CD4+ count (above 400 cells/µL). 

POSTERS 

Discussion 

Clinicians facing HIV-infected p, should consider that cryptococcosis may still occur, 

although a dual, subsequent infection by C. neoformans and C. laurentii is a very 

unfrequent event. The eradication of C. neoformans does not guarantee that another 

Cryptococcus spp. could occur subsequently. Moreover, the polysaccharide antigen assay 

is not predictable for C. laurentii, and the susceptibility studies are mandatory for 

C. laurentii treatment, due to its unpredictable antifungal sensitivity profile. Further studies 

are needed to assess whether antimycotic treatment and prophylaxis against 

C. neoformans may help to select resistant C. laurentii strains. 


PP 3.29 

The Effects of a Supervised Exercise Programme on Self-efficay, Cardiovascular 

Fitness and Quality of Life in HIV/AIDS 

Soula Fillipas, Leonie Oldmeadow, Micheal Bailey and Catherine Cherry 

Soula Fillipas The Alfred Hospital 

Leonie Oldmeadow The Alfred Hospital 

Michael Bailey Monash University 

Katherine Cherry The Alfred Hospital, Burnet Institute and Monash University 

With combination antiretroviral therapy, HIV has become a chronic, manageable medical 

condition. The role of non-pharmacological interventions such as exercise among people 

with HIV is increasing. 

Aim 

To evaluate the effects of a supervised exercise programme (SEP) on self efficacy, 

cardiovascular fitness and quality of life (QOL) status on people living with HIV/AIDS. 

Methods 

A randomised single blinded controlled trial was conducted at a tertiary hospital's 

physiotherapy department. Forty male HIV-infected individuals were randomly allocated to 

an experimental (n=20) or a control (n=20) group. The experimental group was a 

combined aerobic and progressive resisted exercise programme twice weekly, offered to 

all patients of the hospital. The control group participated in an individual walking 

programme twice weekly and attended a monthly group forum. The study duration was 24 

weeks. Outcome measures were a Generic Self Efficacy Scale as a measure of 

perceived self efficacy; 1 minute heart rate response post 3 minute step test; MOS-HIV 

Health Survey as a measure of health related quality of life. Measurements were taken at 

baseline, 2 months and 6 months. Baseline comparisons were conducted using 

chi-square proportion and student t-tests, validated using Wilcoxon rank sum tests. 

Differences between groups were assessed using repeat measures analysis of variance 

on all three time points and validated using repeated measures analysis of variance on 

the change from baseline. 

Results 

The experimental group improved significantly in self efficacy [mean increase 5.3 points 

(p

PP 3.30 

Osteopenia and osteoporosis in among HIV-infected patients treated with antiretroviral 

therapy. A relationship with male gender and protease inhibitor administration 



Introduction 

The aim of our study was to evaluate the prevalence of osteopenia and osteoporosis in a 

homogeneous cohort of patients with HIV infection followed at a single reference centre, 

and to assess their clinical significance, and their possible correlation with demographic 

variables and the selected, background antiretroviral associations. 


All patients were enrolled among the over 1,000 adult subjects with HIV infection referring 

to our tertiary care outpatient centre of S. Orsola Hospital, Bologna, Italy. Bone mineral 

density was measured in lumbar spine and femoral proximal head, by a dual energy X-ray 

absorptiometry (DEXA) technique. 

Results 

A total number of 95 HIV-infected patients (45 males and 50 females), were enrolled until 

now: 12 subjects were naïve to antiretroviral therapy, while the large majority of patients 

(83 cases: 87.4%) were already treated with anti-HIV compounds. Among treated 

individuals, 18 received three nucleoside reverse transcriptase inhibitors (NRTIs), 28 were 

treated with two NRTIs plus one non-nucleoside reverse transcriptase inhibitor (NNRTI), 

and the remaining 37 patients received two NRTIs plus one protease inhibitor (PI) (either 

boosterized or not). As a whole, the overall prevalence of osteopenia and osteoporosis 

according to lumbar T-score was 37.9% and 9.5% respectively, and osteoporosis was 

significantly more frequent in males than in females (20% versus 0%; p

PP 3.31 

Prevalence of depression among AIDS patients on antiretroviral therapy in two 

tertiary care hospitals of Delhi, India 

Shashi Kant, Vivek Lal, Richa Diwan, Ashutosh Biswas, Sanjay Rai 

Shashi Kant, Vivek Lal, Ashutosh Biswas, Sanjay Rai- ALL INDIA INSTITUTE OF 

MEDICAL SCIENCES, NEW DELHI, INDIA. Richa Diwan- LOK NAYAK HOSPITAL, NEW 

DELHI, INDIA 

Objective 

The objective of this study was to determine the prevalence of depression among AIDS 

patients on antiretroviral therapy and to determine the factors associated with it. 

Methods 

Outpatients receiving ART (n= 300) at two tertiary level hospitals were administered an 

interview schedule consisting of questions related to socio-demographic variables, Beck 

Depression Inventory (BDI), Social Provisions Scale (components of which 

included- attachment, social integration, reassurance of worth, reliable alliance, guidance 

and opportunity for nurturance), substance abuse and HIV disease status. Based on BDI 

score, patients were classified either normal (=10). 

Results 

The mean BDI score was 6.23 (SD- 3.84 and range 1-40). Nine percent patients were 

found to be depressed. Logistic regression model identified the following factors to be 

significantly associated with depression- Timing of counseling (OR- 0.027, 95% CI 0.005- 

0.162, p< 0.001), Perceived relief from ART (OR- 0.001, 95% CI 0.000-0.026, p

PP 3.32 

Clinical outcomes in HIV positive patients after dentoalveolar surgery 

KISHORE SHETTY 

UT HEALTH SCIENCES CENTER, HOUSTON 

Introduction 

The purpose of this study was to perform a preliminary test of the hypothesis that patients 

infected with the human immunodeficiency virus (HIV) have an increased risk of 

complications after oral surgery in comparison with HIV-negative patients. 

Methods 

A retrospective cohort study records of HIV seropositive individuals who underwent any 

dentoalveolar surgical procedures between 1999 and 2004 was matched with the records 

of HIV negative control patients. Demographic and clinical information was entered into a 

database that included: indication for surgery, type of surgical procedure, emergent or 

elective surgery, anesthetic type, pre-procedure antibiotics, CD4 count, viral load, white 

blood cell count, hematocrit, serum chemistry and liver functions tests. Peri-operative and 

post-operative events were recorded as complications if they occurred within 30 days of 

surgery and if they were described in the record as a complication or an unexpected 

event. Logistic regression analysis was done to determine the independent effects of HIV 

infection and other potential risk factors for surgical complications. 

Results 

The adjusted rates [(OR=3.12, p=0.02)] of infectious and hematological complications in 

major dentoalveolar procedures were higher among the HIV positive patients then among 

the HIV negative individuals. Variables significantly associated with complications were 

age (OR=1.68), ethnicity (OR=1.97), viral load (OR=2.33) and highly active antiretroviral 

therapy OR=2.45). 

Conclusions 

HIV- seropositive status was found to be an independent risk factor for complications of 

major oral surgical procedures. The most important risk factors for complication of 

surgery in HIV positive individuals were high viral load and absence of antiretroviral 

treatment. 

POSTERS 


PP 3.33 

Rhinopharyngeal carcinoma with a concomitant, local lymphoproliferative disorder, 

both related to an underlying, concurrent HIV and Epstein-Barr virus infection 

Roberto Manfredi, Sergio Sabbatani 


Introduction 

Only two human cells types allow the replication of Epstein-Barr virus (EBV): 

B-lymphocytes and squamous epithelium. Burkitt lymphoma recognizes a pathogenetic 

role for both EBV, and multiple co-factors, influenced by geographic issues, too. 

The nasopharyngeal carcinoma predominates in South-Eastern Asia, where the 

exposure to some cancerogenetic inhalants seems more frequent, but antibodies against 

the early antigen VCA of EBV are commonly found, as well as the isolation of EBV gene 

sequences from neoplastic cells. The staging of rhinopharyngeal carcinoma also includes 

a poorly differentiated variety with a prominent lymphoid infiltrate, which may raise the 

suspect of an extranodal lymphoma, although the resident T-lymphocyte cells are not 

malignant. During HIV disease, malignant lymphomas and EBV-associated 

lymphoproliferative disorders prove more frequent than in the general population, but 

nasopharingeal carcinoma remains an extremely infrequent occurrence. 

Case report 

Our patient, HIV-infected since 20 years and with a long history of inhalatory cocaine 

abuse, 24 months ago developed a remarkable laterocervical lymphadenopathy, whose 

histopathologic study disclosed a polymorphic EBV-associated B-cell lymphoproliferative 

disorder. A CT scan concurrently showed a right nasopharyngeal mass, and detected 

multiple cervical, axillary, and ilar-mediastinal lymphadenopathies. A rhinopharingeal 

biopsy disclosed a poorly differentiated squamous carcinoma, resulting EBV-positive at 

biomolecular testing. A cytotoxic chemotherapy was performed with ten consecutive 

cycles of cisplatinum-fluorouracil-bleomycin, associated with HAART, which achieved 

disease remission. A CT re-staging carried out four months later showed sparse 

parapharyngeal and paravertebral infiltrates, so that the suspected recurrence prompted 

a further radiotherapy course, while the immune recovery was not attained, as expressed 

by a CD4+ lymphocyte count of 83 cells/µL, despite virologic control of HIV replication. 

After four more months of follow-up, another disease staging showed disease remission. 

Conclusions 

Our patient suffered from two distinct malignant and pre-malignant disorders, with some 

intriguing pathogenetic associations mainly linked to EBV, but also HIV and related 

immunodeficiency, and perhaps the chronically inhaled cocaine as a local pathogenetic 

co-factor. Both squamous carcinoma and lymphoproliferative disorder of the nasopharynx 

are more frequent in the immunocompromised host, and deserve further pathogenetic 

studies, to clarify the shared or addictive role of some viral and environmental risk factors, 

in the pathogenesis of nasopharyngeal carcinoma, especially when concurrent HIV and 

EBV infection are of concern. 


PP 3.34 

Fatal Disseminated HIV-Associated Prostatic Adenocarcinoma Presenting with 

NON-Specific Features 

Roberto Manfredi, Ciro Fulgaro, Sergio Sabbatani, Nicola Dentale, Giorgio Legnani 


Introduction 

Prostate cancer is a very infrequent occurrence in persons aged 55 years or less, and it 

has been rarely reported in HIV-infected patients (ten overall cases so far), therefore an 

increased incidence compared with the general population has not been established, 

although a younger age seems more frequent among population with HIV disease. 

Case report 

We report a case of metastatic prostate cancer occurred in a 53-year-old HIV-infected 

man, admitted due to non-specific signs and symptoms: impaired general conditions, 

fever, weight loss, fatigue, and exertional dyspnea. A remarkable anemia and an aortic 

systolic murmur were the prominent initial findings, while AIDS-related conditions were not 

suspected due to a sustained CD4+ lymphocyte count and a contained viremia, which 

never required antiretroviral therapy. Repeated red blood cell transfusions and an 

empiric, combined antimicrobial therapy were promptly carried out, under the suspicion of 

infectious endocarditis, but no appreciable improvement of clinical conditions was 

achieved. Subsequently, our patient complained of a increasingly severe pain at the root 

of his left thigh, together with overcoming dysuria and urgency, but also an urinary tract 

infection was rapidly ruled out. During the diagnostic workup for an HIV-associated fever 

of undetermined origin, a bone marrow biopsy disclosed a metastatic prostatic cancer, 

with elevated prostate specific antigen (PSA) and acid phosphate levels. 

An abdominal-pelvic ultrasonography and computerized tomographic scan allowed to 

detect a dyshomogeneous endopelvic expansive mass which extrinsic compression of the 

urinary bladder, and involvement of the last lumbar vertebra, large portions of pelvis, and 

the proximal epiphysis of the right femur. A skeleton scintigraphy pointed out multiple 

hypercaptation areas with involvement of cranial, cervical, dorsal, lumbar, and sacral 

vertebrae, as well as the pelvis and upper portions of both femurs. Despite therapeutic 

attempts, our patient deceased after seven weeks due to an overwhelming disseminated 

intravascular coagulation (DIC). 

POSTERS 

Conclusions 

The non-specific clinical presentation of our case report of prostate adenocarcinoma 

(mimicking other generalized or focal illnesses), and the final, lethal complication (DIC) 

pose striking problems related to the differential diagnosis during HIV disease, while the 

rapid evolution into an advanced, complicated, and widely metastatic disease with 

remarkable bone marrow invasion which preceded the appearance of local 

signs-symptoms, and the lethal overwhelming DIC, deserves careful attention by 

specialists who care for HIV-infected subjects. 


PP 3.35 

Large vessel damage due to accelerated atherosclerosis observed during HIV 

disease. Life-threatening rupture of an aortic aneurism in an HIV-infected patient 



Introduction 

Accelerated atherosclerosis and its multiform clinical correlates are of increasing concern 

among HIV-infected patients (p) undergoing HAART. 

Case report 

A 55-year-old HIV-infected heterosexual male had HIV infection known since four years, 

and started antiretroviral therapy 19 months before with associated ddI-ABC-EFZ. Save a 

moderate dyslipidemia disclosed after 6 months of HAART (maximum serum cholesterol 

level 255 mg/dL with LDL cholesterol 147 mg/dL, and maximum triglyceride levels 474 

mg/dL), controlled by alternate statins-fibrates, no risk factors for heart-large vessel 

diseases were present, with a mute personal-family history, no tobacco-alcohol 

consumption, arterial hypertension, diabetes mellitus, and overweight. Eleven months 

after HAART initiation (8 month ago), abdominal pain and a pulsating mass at palpation 

led to a ultrasonography and CT-scan diagnosis of a thoracic-abdominal type III aortic 

aneurism; at that time, plasma HIV viremia was undetectable, and CD4+ lymphocyte 

count was 253 cells/µL. An endoprosthesis was positioned, and complications were 

carefully excluded by imaging and functional techniques. Seven months later, a sudden 

abdominal pain was due to the rupture of an abdominal-suprarenal aortic aneurism, which 

deserved immediate positioning of an endoprothesis type Talent between the older 

thoracic graft and the suvrarenal aortic prosthesis, and the revascularization of renal and 

upper mesenteric arteries. As repeatedly checked by doppler-ulstrasonography and 

CT-MRI scans, no sequelae occurred, and a normal kidney, gut, liver, and heart function 

were maintained. HAART was successfully continued (with undetectable viremia and a 

CD4+ count of 317 cells/µL), daily gemfibrozil was given for hypertriglyceridemia (232 

mg/dL) together with ticlopidine, while beta-blockers were suspended three months after 

surgery. 

Discussion 

Asymptomatic, symptomatic, and ruptured aortic and large vessel aneurisms were 

anecdotally described in HIV-infected p (around 30 reported cases), but a double 

intervention after rupture of a pre-treated aortic aneurism has no precedents. While in the 

HAART era mycotic aneurysms followed the drop of opportunism, the increasing life 

expectancy, the dysmetabolism, and the endothelial dysfunction due to possible direct 

effects of HIV and multiple drug-related variables (especially when multiple-recurring 

aneurisms occur), could represent risk factors for an increased morbidity of large vessel 

vasculopathy. Clinicians should not underestimate these disorder, while therapeutic 

guidelines should be the same of non-HIV-infected p [J Endovasc Ther 2005;12:405]. 


PP 3.36 

Impact of syphilis infection on HIV viral load and CD4 cell counts in HIV-infected 

patients 

Palacios R., Jiménez-Oñate F., Aguilar M., Galindo M.J., Rivas P., Miralles P., Ríos M.J., 

Knöbel H., Ena J., Arranz J.A., de la Torre J., Márquez M., Santos J. 

Hosp. Virgen de la Victoria, Málaga, Spain, Hosp. Carlos Haya, Málaga, Spain, Hosp. 

Virgen del Rocío, Sevilla, Spain, Hosp. General, Valencia, Spain, Hosp. Gregorio 

Marañón, Madrid, Spain, Hosp. Carlos III, Madrid, Spain, Hosp. Virgen Macarena, Sevilla, 

Spain, Hosp. Xeral, Vigo, Spain, Hosp. del Mar, Barcelona, Spain, Hosp. Marina Baixa, 

Villajoyosa, Spain, Hosp. Príncipe de Asturias, Alcalá de Henares, Spain, Hosp. Costa del 

Sol, Marbella, Spain 

Objectives 

Although increases in HIV viral load (VL) and decreases in CD4 cell count have been 

suggested in HIV-patients with syphilis infection, the interaction between syphilis and 

these variables is not well defined. Our aim was to assess the effect of early syphilis on 

HIV VL and CD4 cell count in HIV-infected patients, and to analyze factors associated with 

changes in HIV VL and CD4. 

Methods 

multicenter study of a series of HIV patients diagnosed with early syphilis infection during 

2004-2005. All patients had HIV VL and CD4 cell count measurements during the syphilis 

infection, and, at least another determination before and/or after this event. Patients who 

started or changed their HAART regimen during the analysis period were excluded. 

Statistical program: SPSS ® 12.0. 

Results 

151 HIV patients with early syphilis were identified in 12 Spanish hospitals, 118 satisfied 

the inclusion criteria for study entry. 95.7% were men, the mean age was 38.0 years, 

83.8% were men who had sex with men; 59 (50.4%) were on antiretroviral therapy at 

diagnosis of syphilis, and in 38 (32.5%) cases, diagnosis of HIV and syphilis infection were 

coincident. CD4 cell counts were lower during syphilis than before infection (596 vs 502 

cells/mL; p=0.0001), and than after syphilis treatment (509 vs 597 cells/mL; p=0.0001). 

HIV VL increased in 28.0% patients during syphilis. The only factor associated with HIV 

VL increase was not being on HAART (OR 3.19, CI 95% 1.02-10.01; p=0.04), and the only 

factor associated with a CD4 decrease >100 cells/ L during syphilis was the prior CD4 cell 

count. 

POSTERS 

Conclusions 

syphilis infection was associated with decreases in CD4 cell count and increases in HIV 

VL in almost one third of the patients. In this series more than two thirds of the syphilis 

cases were diagnosed in prior known HIV-infected patients. 


PP 3.37 

No Interference between Syphilis and Virological and Immunological Markers of HIV 

Disease 

Roberto Manfredi, Sergio Sabbatani, Leonardo Calza 


Introduction 

After the recent evidences of a recrudescence of STD during HIV disease, since the year 

2001 we carried out an observational study on a cohort of over 1,000 HIV-infected patients 

(p). 


Forty-nine p (33 homo-bisexuals and 16 heterosexuals, aged 23-58 years) were identified 

as novel cases of syphilis (S) (secondary S in 39 cases, primary or latent disease in the 

remaining episodes). They were assessed and treated based on standardized protocols, 

and followed for the 12-21 subsequent months. 

Results 

Immunological data including >6 months preceding S and >9 months following S were 

available. All p save six took HAART, according to current international recommendations. 

During the >15 month observation period, no statistically significant trend of laboratory 

parameters of HIV disease was seen in our HIV-infected p co-infected with S. 

Discussion 

Although interaction between S and HIV were not deeply investigated, the HIV-related 

quantitative and functional damage of cell-mediated immunity could modify the course of 

S. Concurrently, during S an impairment of cellular migration and clearance, and cytokine 

network, were documented, together with an increased lymphoid cell apoptosis. However, 

it remains difficult that a non-opportunistic disease like S may trigger pathogenetic 

mechanims capable of infuencing significantly the HIV disease course, especially when a 

HAART treatment concurs. While we agree with the concerns related to STD in p with HIV 

or exposed to HIV, differently from recent literature data (Buchacz K, AIDS 2004;18:2075), 

in our experience syphilis does not seem to modify the laboratory course of HIV infection. 

Although health care providers should take into careful consideration all suspected STD 

in HIV-infected p, only prospective case-control studies may answer questions associated 

with the potential existence of bidirectional pathogenetic and clinical interactions between 

HIV infection and S. 


PP 3.38 

Follow up Study - Oral Candida Flora from Brazilian HIV 1-Infected Children in the 

HAART Era 

NADJA R. MELO1*, VITORIA V. P. CULHARI,1 , HIDEAKI TAGUCHI2, AYAKO SANO2, 

KAZUTAKA FUKUSHIMA2, STEVEN L. KELLY3 and M. MARLUCE S. VILELA1 

1Center of Pediatric Investigation, University of Campinas State, Brazil, 2Research Center 

for Pathogenic Fungi and Microbial Toxicoses, Chiba University, Chiba, Japan and 

3School of Medicine, Swansea University, Wales 

Objective 

This study characterized the Candida oral flora from 52 Brazilian HIV 1-infected children, 

comparing the Candida species identified in two periods before (PI) and under (PII) the 

HIV Protease Inhibitor therapy. 

Materials and Methods - Collection of isolates 

Isolates of oral cavities from 52 HIV-infected children were investigated in two different 

periods. Oral swabs were collected from these 52 children during the period when they 

were under double antiretroviral therapy (PI), and when they started HAART including 

protease inhibitor (PII). All oral swabs were plated on chromogenic agar. 

Characterization of isolates 

The isolates were identified according to the standard technique described by Sandven 

(1990). 

Antifungal susceptibility test 

MICs were determined by broth microdilution method of National Committee for Clinical 

Laboratory Standards (NCCLS 2002). 

Results 

There was a significant increase of non-albicans isolates from 9.6% to 28.8% (p=0.005) 

between PI and PII groups respectively. In the PII the second most frequent species was 

C. tropicalis (n=9) followed by C. parapsilosis (n=8). Rare species found in the PII 

included C. dubliniensis, C. norvegensis, C. humicula and C. rugosa. All isolates 

investigated were susceptible to amphotericin B. Most of C. albicans and non-albicans 

isolates were susceptible to fluconazole, voriconazole, itraconazole and ketoconazole. 

However one of seven C. tropicalis isolates was resistant to fluconazole (MIC > 64 µl/ml) 

and one C. albicans-B isolate showed cross-resistance to all azoles and amphotericin 

tested. 

POSTERS 

Conclusions 

Higher diversity of Candida species was found in group PII, and a significant emergence 

of children colonization by non-albicans species with varied antifungal susceptibility. This 

study represents the first follow up investigation concerning oral Candida flora and 

antifungal susceptibility in Brazilian HIV 1-infected children. 


PP 3.39 

Faecal flora, diarrhoea associated with protease inhibitors in HIV-infected patients 

F. de Salvador-Guillouët, H. Carsenti-Dellamonica, X.Hebuterne, F.Girard-Pipau, 

J. Durant, P.Dellamonica 

Hôpital de l'Archet 1- service Infectiologie - BP 3079 - 06202 Nice cedex 3 

Diarrhoea and abdominal pain with varying degrees of severity are frequent in HIVinfected 

patients and diarrhoea is one of the main causes of alteration of patients' quality 

of life. 

Objectives 

the aim of our study was to explore intestinal disorders associated with nelfinavir, a 

protease inhibitor (PI). 

Methods 

A prospective open study was conducted and included: 5 individuals with stool samples 

before and after treatment with nelfinavir (two healthy subjects and 3 HIV-infected 

patients), one untreated HIV-infected patient, 9 on treatment with nelfinavir during 1 month 

to 1 year and with varying degrees of intestinal dysfunction. A total of 20 stool samples 

were available and immediately frozen at -20°C (within less than 2 hours) 

Patients gave their informed consent Known bacterial or parasitic causes of diarrhoea 

were ruled out. 

Methods 

samples were analyzed for faecal flora by a gel-separation procedure for double stranded 

deoxyribonucleic acid (TGGE) and proteolytic activity was expressed as log10 of trypsin 

units that hydrolysed azocaseine per hour and per gram of faeces and determined in 

crude homogenate and soluble fraction. 

Results 

For treated HIV-infected patients, similarity percentage for TGGE before and after 

treatment was 86.7%. TGGE profiles were already disturbed and looked abnormal at the 

initial TGGE analysis study. PI did not appear to change the faecal flora significantly. 

Similarity percentage indicated a disturbance in faecal flora only in healthy subjects who 

took the treatment during three weeks. They did not have any diarrhoea, only soft stools. 

Proteolytic activity was enhanced in PI-naïve HIV-infected patients (9.4+3.6 and 4.5+2.0 

logTrypsine U/ml) and decreased after = 2 months' nelfinavir treatment (6.3+1.4 and 

2.6+0.08 logTrypsine U/ml) in crude homogenate and soluble fractions, respectively. The 

level of proteolytic activity was similar to that of healthy patients only after more than one 

month's treatment 

Conclusion 

this pilot study concerns a small number of samples due to difficulties in obtaining fresh 

stool samples. However HIV-infected patients appear to have a major disturbance of their 

faecal flora with high proteolytic activity prior to treatment that decrease after PI treatment. 

Our study suggests that an independent factor may have altered the flora before both 

samples were taken. Such elevated levels of faecal proteases in this disease may play a 

role in subsequent damage of the intestinal mucosa. These preliminary results merit 

further investigation. 


PP 4.1 

Evaluation of a Triple Therapy Associating 2 NRTI + EFAVIRENZ Versus 2 NRTI + 

INDINAVIR in HIV-1 Positive patients with Less than 100 CD4/mm 3 AT Initiation 

TANON A 1 , EHOLIE S 1 , ELLOH F 1 , DJADJI A 1 , KANGAH C 2 , CHENAL H 3 , 

BISSAGNENE E 1 , KADIO A 1 . 

1 

Infectious and tropical diseases department - BP V 3 CHU de Treichville - Abidjan - Côte 

d'Ivoire. 

2 

Ambulatory Care and counseling Unit of Abidjan 

3 

Center of Bioclinical Research of Abidjan 

Backgrounds 

To compare the therapeutic efficiency, the tolerance and the adherence of 2 therapeutics; 

the association of 2 INRT + efivarenz (EFV) versus 2 INRT + Indinavir (IDV) to immuno 

depressed patients having a rate of CD4

PP 4.2 

Triple therapy adherence in HIV infected adults in Abidjan, March to September 

2002. 

A Tanon¹, S Polneau 2 , E Ehui¹, T Aba¹, I Ouattara¹, A Kassi¹, S Eholié¹, E Bissagnéné¹. 

¹Infectious and tropical diseases department, BP V 3 Abidjan 01 - CHU Treichville - 

Abidjan, Côte d'Ivoire ; 

²Statistic department - Pharmaceutical and Biological Unit of Research - University of 

Cocody- Abidjan, Côte d'Ivoire 

Objective 

To evaluate the adherence to HAART and identify the factors associated with bad 

adherence. 

Methods 

A transversal and multicentric study made from March to September 2002 in Abidjan. The 

adherence was evaluated from a questionnaire made in 7 days. The rate of adherence 

was calculated as the number of inserted drugs really divided by the number of units which 

should have been inserted in 7 days. Factors associated to the adherence were studied 

on multivarious logistic decline. 

Results 

308 patients (sex ratio H/F : 1,1) were interviewed. The middle duration under treatment 

was 19,8 months ; 79 % of patients were in first line of the treatment and 21 % in second 

or third line. The median rate of adherence was estimated at 76, 13 % (interquartile 

interval 65,5 -90,5 %) ; 160 patients (52 %) had a rate less than 95 % and were so 

considered as imperfectly adherents. Main causes of side effects (27 %), the lack of 

financial means (20%), the risk of stigmatization and discrimination proportional to the 

socio cultural environment implying tradipractitioners (18 %), the complexity of anti 

retroviral treatments (18 %). In multivarious analysis, variables associated to the imperfect 

adherence were a high education level (OR=0,492 , IC = 0,27 - 0,89, p = 0,017), the 

duration of treatment more than one year (OR=0,584, IC = 0,33 - 1,01, p =0,054), the bad 

information of patients concerning the importance of the adherence (OR : 0, 28 IC 95 % 

0,08 - 1,01) and the patients commitment to follow or not his anti retroviral treatment 

(OR=3,121, IC= 1,26 - 7,74, p = 0,014). 

Conclusion 

Our results show real adherence difficulties linked to anti retroviral treatment in Abidjan 

since the first months. So it is necessary to find mechanisms as at institutional level as the 

one of the patient to optimize the adherence which is the guarantee of therapeutic 

success. 

Key words : adherence, AIDS, Antiretroviral treatment, Abidjan, Côte d'Ivoire, Africa. 


PP 4.3 

Patterns and Predictors of Adherence to Antiretroviral Medications in Older Adults 

Living with HIV/AIDS in the United States 

Bernadette Davantes Heckman, 1 Arlene Kochman, 2 Nathan Hansen, 2 Sharon Nuefeld, 

2 

Kathleen Sikkema, 2 Timothy Heckman 1 

1 

Department of Psychology, Ohio University, Athens, OH, 45701, USA 2 Department of 

Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 

06520, USA 

Objectives 

The U.S. Centers for Disease Control and Prevention (CDC) predicts that by 2015, 50% 

of all persons living with HIV/AIDS in the United States will be 50 years of age or older. 

Past research, conducted primarily with small convenience samples, has found relatively 

high levels of adherence to antiretroviral medications in older adults living with HIV/AIDS; 

approximately 75% report 100% adherence over a one-week time period. The current 

study utilized a larger and more geographically-diverse sample to characterize rates and 

predictors of adherence to antiretroviral medications in persons 50-plus years of age living 

with HIV/AIDS. 

Methods 

Pre-intervention data were provided by 231 HIV-infected persons 50-plus years of age 

enrolled in a randomized clinical trial of two AIDS mental health interventions designed 

specifically for HIV-infected older persons. Participants were recruited in New York City 

(n=163), Columbus, OH (n=34) and Cincinnati, OH (n=33). Audio-computer assisted self 

interviews assessed participants' psychological symptomatology, social support, ways of 

coping, coping self-efficacy, and AIDS-related shame. The average participant (M age =54.2 

years) was male (67%), African American (51%), and self-identified as gay/bisexual 

(55%). 

Results 

A 100-point Likert scale assessed the consistency in which participants took all of their 

prescribed HIV medications during the past week (0%="Not at all" to 100%="All the time"). 

Participants' mean response was 93.0% (SD=18.2, Min=0, Max=100). Adherence to 

antiretroviral medications was unrelated to participants' gender, race, education, or 

number of years living with HIV disease (all ps > .15); however, greater adherence was 

found in persons who had health insurance (M=94.4%) compared to those without 

insurance (M=80.1%), F(1,187)=9.9, p < .002. While adherence was unrelated to 

participants' most recent CD4 cell count (p > .20), greater adherence was predictive of 

lower levels of HIV viral load, r(151)= -.41, p < .001. A series of univariate regression 

analyses revealed that, when controlling for health insurance status, greater medication 

adherence was associated with fewer depressive symptoms, beta= -.27, p < .001; lower 

levels of AIDS-related shame, beta= -.15, p < .02; less loneliness, beta= -.17, p < .01; 

elevated perceptions of social support, beta= .16, p < .02; and greater coping self-efficacy, 

beta= .17, p < .009 (standardized beta coefficients). Medication adherence in this sample 

was unrelated to knowledge about living with HIV/AIDS, beta= .02, p > .80; 

alcohol use, beta= -.04, p > 50; substance use, beta= -.06, p > .35; and cognitive 

functioning, beta= -.04, p > .50. 

POSTERS 


In a hierarchical multiple regression analysis, in which health insurance status was entered 

in Block 1 and the significant univariate predictors of adherence were entered in Step 

2, only depressive symptomatology predicted adherence above-and-beyond participants' 

health insurance status, R 2 =12%, F(6,224)=4.6, p < .001. 

Conclusions 

Sixty-five percent of participants reported 100% adherence to antiretroviral medications in 

the past week. The small subgroup of participants who experienced difficulty adhering to 

medication regimens consisted of individuals who lacked health insurance and who 

reported more depressive symptoms. Adherence-promotion interventions for this small 

group of adherence-challenged HIV-infected older persons should be evaluated in future 

research. 


PP 4.4 

Experience with Art Adherence Counselling at Muhimbili National Hospital, Dar es 

Salaam, Tanzania 

Millen R., Bakari M, Mugusi F, Aris E, Nyamtema AS, Janabi M, Josiah R, Swai H. 

HIVIS Project-MUCHS, DAR ES SALAAM,TANZANIA 

Background 

In July 2004, the Tanzanian Ministry of Health initiated a pilot care and treatment program 

at the Muhimbili National Hospital (MNH). The pilot program was designed to inform the 

national scale-up of antiretroviral therapy (ART). The goal of the pilot program was to 

initiate 1,300 patients on ART over a period of three months. We report our initial 

experience in offering adherence counseling to these clients 

Methods 

Clients were seen at the MNH HIV/AIDS clinic from July 2004 to October 2004. All eligible 

patients were offered ART adherence counseling prior to therapy initiation and thereafter 

at every re-fill appointment. ART was initiated only after both the counselor and client 

having been satisfied with the readiness of the client to start therapy. 

Assessment of degree of adherence was by self-report as well as pharmacy re-fill 

performed quantitavely, while patient's attitudes to the exercise and problems associated 

with offering adherence counseling were ascertained using qualitative methods 

Results 

By 30 th September 2004, 1,286 patients were enrolled in care and 881 patients were put 

on ART having undergone adherence counseling. More than 65% of the enrollment 

occurred in the first eight weeks of the pilot program, indicating strong demand for HIV 

care and treatment services among people living with HIV/AIDS (PLWHA) in Dar es 

Salaam. By the end of October 2004, a total of 1655 patients were in care and 1,172 

(70.82 %) on ART. Patients on ART included 59% women, 31% men, and 10% children. 

The loss to follow-up rate was 11%. 

Overall, clients reported good satisfaction with the quality of care offered at the clinic, and 

85% of clients demonstrated good understanding on issues pertaining adherence to ART. 

At follow-up, it was noted clients achieved 95% adherence with ART. 

However, long client waiting-times emerged as a significant problem when the clinic 

caseload exceeded 100 visits per day. 

POSTERS 

Conclusions 

The achievements and experiences of the MNH ART clinic showed that good adherence 

is possible in a resource poor setting with extreme staff shortages and should be started 

early before initiation of ARV therapy. 

However, as such progammes scale-up, they should be prepared to face up huge practical 

challenges. 


PP 4.5 

A Prospective Study of Antiretroviral Drug Adherence in HIV-Infected Patients in 

Oman 

S. H. S. Al Dhahry#, Z. M. H. Al-Bimani#, M. R. M. Y. Al Lawati*, E. M. Scrimgeour#, F. A. 

K. Al Lawati**, A. A. S. Balkhair** 

#College of Medicine & Health Sciences, and **Sultan Qaboos University Hospital, 

Muscat, OMAN, *Al Nahdha Hospital, Muscat, OMAN. 

Objectives 

Highly active antiretroviral therapy (HAART) has changed the natural history of HIV-1 

infection from an almost invariably fatal to a chronic disease. However, the effectiveness 

of HAART is often limited by several factors, including the emergence of drug resistance 

mutations. In a previous study in Oman, virologic failure was observed in 93% of HIV-1 

infected patients on HAART. However, virus isolates from most patients had no drug 

resistance mutations. Thus, a study was carried out to determine the degree of drug 

adherence and its relationship to virologic and immunologic outcomes, and to identify 

barriers to, and predictors of adherence. 

Methods 

Thirty four HIV-1 infected Omani patients on HAART were enrolled into a prospective 

study. In most (88%) patients, the treatment regimen consisted of two reverse 

transcriptase inhibitors and one protease inhibitor. Adherence to antiretroviral (ARV) drugs 

was assessed over a 6-month period using patient self report and pill count measures. 

Blood samples were collected at baseline, at 3 and 6 months for HIV viral load assay and 

CD4+ lymphocyte counts. 

Results 

Self report adherence fluctuated from 81% to 98% (mean 90%), and pill count adherence 

varied from 84% to 93% (mean 88%). Patients were categorized as having poor (95%) adherence. Fifty percent and 52.2% 

of patients had excellent adherence when measured by self report and pill count 

respectively. An increase in level of adherence was associated with a decrease in VL and 

an increase in CD4+ cell counts. The most consistent observation was that excellent 

(>95%) adherence resulted in undetectable virus and was associated with higher CD4+ 

counts in a significantly higher number of patients than lower levels of adherence. 

Common factors that contributed to poor adherence were side effects from prescribed 

ARV drugs, running out of drugs, forgetting to take medications, and being away from 

home. Indinavir was associated with side effects in more patients than other drugs. In 

contrast, Combivir was better tolerated. 

Conclusion 

Approximately half of Omani HIV-infected patients on HAART do not achieve levels of 

adherence that are associated with durable suppression of virus replication. Thus, there 

is an urgent need to develop measures aimed at improving ARV drug adherence. 


PP 4.6 

Impact of free and universal access to antiretroviral treatment on the survival 

among Brazilian children with AIDS 

Matida LH 1 , Ramos ANJ 2 , Moncau JEC(3), Marcopito LF 3 , Marques HHS 4 , Succi RCM 3 , 

Della Negra M 5 , Hearst N 6 

1 

National Program of STD/AIDS-Brazil; 2 Federal University of Ceará-Brazil; 3 Federal 

University of Sao Paulo-Brazil; 4 University of Sao Paulo-Brazil; 5 Institute of Infectology 

"Emilio Ribas"-Sao Paulo/Brazil; 6 University of California, San Francisco-EUA 

Issues 

Besides the existing social inequality and the differences on access to health services, 

Brazil with his vast geographical area, offers free and universal access to antiretroviral 

treatment (ART) for AIDS patients. This technical and political attitude has brought substantial 

improvement in survival among pediatric patients with HIV, in Brazilian regions. 

Description 

We obtained data on retrospective cohort study in 10 Brazilian cities to examine trends in 

diagnostics and survival with a representative sample of AIDS cases in persons younger 

than 13 years old listed in the Brazilian national AIDS registry with years of diagnosis 

between 1983 and 1998 and followed until 2002 (N for analysis = 1,154). Date of last 

clinical contact was used as a censor date for children not known to have died. 

Lessons learned 

Survival time increased steadily and substantially in all regions despite the observed 

differences. The survival probability on 60 months after the diagnosis for the period from 

1988 to 1992 was 0.246 (CI 95%: 0.150-0.356) and it increased to 0.605 (CI 95%: 

0.521-0.680) for the 1997 to 1998 period in children followed up to 2002. Among children 

infected by maternal transmission, the median time since birth to diagnosis was 

12.2 months, and in the Northeast region this time was 18.3 months, and in the Southeast 

region belonged to 4.7 months. The Brazilian experience thus provides the first evidence 

regarding the impact of such treatment on the survival of perinatally acquired AIDS cases 

in the developing world. 

POSTERS 

Recommendations 

A free and universal access to ART, even in a country that lacks an ideal health 

infrastructure, can make a substantial difference in survival. These results argue strongly 

for making such treatment available to children elsewhere in the developing world. 


PP 4.7 

Telephone-Based Coping Improvement Group Intervention for Persons 50 Years of 

Age or Older Living with HIV/AIDS in the United States 

Timothy G. Heckman 

Department of Psychology - Ohio University, Athens, OH 45701, USA 

Objectives: Through December 2003, more than 57,000 persons in the United States were 

55 years of age or older when they were diagnosed with AIDS. Historically, older adults 

have accounted for approximately 10% of all AIDS cases in the United States. However, 

it is now believed that 28% of all persons currently living with AIDS in the U.S. are 50-plus 

years of age. As the population of older adults living with HIV disease continues to 

increase, mental health interventions are urgently needed for this group. In response to 

this need, this research examined if a coping improvement group intervention delivered 

via teleconference technology could facilitate the adjustment efforts of 90 persons 50-plus 

years of age living with HIV/AIDS who were diagnosed with depression. 

Methods: The 90 study participants (mean age=54.4 years; 52% White; 62% Male) were 

recruited through non-governmental organizations (NGOs) in Pittsburgh, PA; Cincinnati, 

OH; Buffalo, NY; and Phoenix, AZ. Recruitment materials were distributed to participants 

via mail, home visits, and placement in high traffic areas of NGOs. The study used a 

lagged treatment, control group design, in which 44 participants were assigned to an 

"Immediate Intervention" condition and 46 to a "Delayed Treatment" condition. Immediate 

Treatment participants completed a pre-intervention assessment, received the 

intervention, and completed post-intervention and 3-month follow-up assessments. 

Delayed Treatment participants completed two pre-intervention assessments, received 

the intervention, and then completed a post-intervention assessment. Self-administered 

surveys assessed participants' depressive and psychological symptoms, life-stressor 

burden, social support, ways of coping, and coping self-efficacy. The telephone-delivered, 

12-session coping improvement group intervention was guided by Lazarus and Folkman's 

Transactional Model of Stress and Coping and used cognitive-behavioral strategies to 

improve participants' skills in stress appraisal, coping decisions, and obtaining social 

support. 

Results: ANCOVA using intent-to-treat strategies indicated that, relative to Delayed 

Treatment participants, Immediate Treatment participants reported greater reductions in 

psychological symptoms (p < .08), life-stressor burden (p < .06), and use of avoidant 

coping and significant increases in coping self-efficacy (p < .07). Immediate Treatment 

participants maintained these changes at 3-month follow-up. Within-group analyses 

indicated that, after receiving the intervention, Delayed Treatment participants reported 

significant reductions in psychological symptoms (p < .08) and life-stressor burden 

(p < .05) and increases in coping self-efficacy (p < .01). A series of post-hoc multiple 

regression analyses were conducted to determine if intervention-related increases in 

coping self-efficacy and reductions in avoidant coping mediated Immediate Treatment 

participants' changes in psychological symptoms and life-stressor burden. These analyses 

indicated that participants' increases in coping self-efficacy (and not decreases in the use 

of avoidance coping) were responsible for much of the reduction in participants' 

psychological symptomatology and perceptions of life stress. 

Conclusions: Data from this preliminary randomized clinical trial provide initial evidence 

that psychological well-being and coping self-efficacy can be improved in HIV-infected 

older adults through participation in an age-appropriate, telephone-delivered, coping 

improvement group intervention. Future research evaluating this intervention approach 

should be conducted with larger and more geographically-diverse samples of older adults 

living with HIV/AIDS. 


PP 4.8 

Management of Nutrition-related Symptoms Among People Living with HIV/AIDS 

under Aanti Retroviral Therapy 

NDIR A, DIOUF A, Ndome M and CISSE D. 

1.HIV Department -Ministry of Heath and Prevention, HIV Department -Ministry of Heath 

and Prevention, Dakar, Senegal, 2.Nutritional Department - Dakar university, Faculty of 

Sciences, Dakar, Senegal, 3. Catholic Relief Service -Dakar 4.Helen Keller International, 

Regional office of Africa -Dakar, Dakar, Senegal 

Background 

Malnutrition is considered as a cofactor of disease progression in HIV/AIDS patients. 

Managing the interactions between food and nutrition and antiretroviral therapy is a 

critical factor in the extent to which the therapy is effective in delaying the progression of 

the disease. 

Objective 

To assess the nutritional knowledge and practices of HIV patients under ART and the 

availability of support regarding management of nutrition-related symptoms. 

Methods 

205 outpatients under ART were studied in 9 HIV care centres of Senegal. 

Anthropometrical parameters were measured. Nutritional management symptoms were 

evaluated using a questionnaire and focus group discussion. Nutrition support was 

obtained among health workers and HIV centres. 

Results 

Average age was 38+/-9 years. BMI was normal (21.8+/-4.1) but 20% of patients were 

malnourished (BMI

PP 4.9 

The significantly different profile on lipid metabolism and its correlates, caused by 

efavirenz compared with Nevirapine 



Introduction 

Altered metabolism represents an emerging feature of HIV-infected patients (p) treated 

with HAART, but limited informations are avilable regarding the two non-nucleoside 

reverse transcriptase inhibitor (NNRTI): respectively, efavirenz (E) and nevirapine (N). 


Among over 1,000 p treated with HAART for over 12 months, the metabolic pattern of 

NNRTI was assessed according to three different backgrounds. The first one included 

antiretroviral-naïve p starting a NNRTI-based regimen;the second included a large 

spectrum of p experienced with two to ten therapeutic lines (but remained still 

NNRTI-naïve); the third group included p who added for the first time a NNRTI only on late 

rescue therapies containing four drugs or more (and including protease inhibitors). 

Results 

Three hundred and 86 p treated with E were compared with 334 p taking N in our 

prospective observational survey lasting 12 to 30 months, by a multivariate analysis of 

serum lipid and glucose levels, and other metabolic abnormalities. Among the 213 p who 

were naïve to antiretrovirals, an altered triglyceridemia was more common (p

PP 4.10 

Evolution of HIV1 infected patient profile treated by Enfuvirtide (Fuzeon ® ) 

Drogoul-Vey MP 1 , Frixon-Marin V 1 , Ravaux I 2 , Mars-Kallee ME 3 , Gastaut JA 1 , Gallais H 2 , 

Poizot-Martin I 1 

1 

CISIH Hôpital Sainte Marguerite; Marseille 

2 

Service Maladies Infectieuses, La Conception; Marseille 

3 

Roche Pharma France 

Introduction 

Fuzeon ® ( enfuvirtide) has proven its efficacy and good tolerability through toro trials. Its 

optimal benefit has been demonstrated for patients with at initiation CD4 > 100/mm 3 , 

viraemia (VL) < 5log10, the number of antiretrovirals (ARV) used < 10 and combined with 

one or two potentially active other ARV. However its prescription is still restricted probably 

due to its galenic form. We conducted a multicentric prospective cohort study to evaluate 

the evolution of patient profile treated with Fuzeon ® . 

Method 

From December 2003 to June 2005, all HIV1-infected patients who have started HAART 

including Fuzeon ® in 2 units of CISIH of Marseilles (France) were included in a 6 month 

prospective cohort study. At baseline viro-immunological status and clinical and 

therapeutic history were recorded. Patients were classified in 2 groups in relation to 

Fuzeon ® initiation prior or posterior of Consensus Recommendations publication (CRP) in 

may 14 th 2004. 

Results 

30 patients were included (22 males, median age 42 years, 30% in stage C of CDC 

classification). Sixteen of them (53%) were HCV coinfected. All were heavily pretreated 

(median of ARV exposure 9 years with a median of 12,5 drugs and 8,5 regimen used). 

Twelve patients have started Fuzeon ® before and 19 patients after recommendations. 

At baseline the majority of patients (64%) had CD4 > 100/mm 3 , a VL < 5log10 but with 

prior utilisation of more than 10 ARV with no difference regardless the period of 

prescription. Among patients treated after CRP, we noted at baseline a higher median CD4 

count (225/mm3 versus 118/mm 3 ) and a larger use of new drugs (25% versus 78% of 

cases; p = 0.01). 

At M6, VL was < 50 cp/ml in 32% of patients and median CD4 cells count had increased 

from 182 to 273/mm 3 (OT analysis). Regarding the period of prescription no difference was 

observed. 

POSTERS 

Conclusion 

In this cohort, Fuzeon ® was initiated in patients with an optimal VL and CD4 count but a 

too important past of ARV used. This issue is balanced by a larger use of new drugs in 

actual favourable context. 


PP 4.11 

Self-Evaluation Investigation of patients treated by Antiretoviral Therapy 

B.COUREAU*, B.PAVY*, J.JOACHIM*, T.DANTIN*, F.LANET*, R.GUILHAUMOU*, 

J.GRASSI*, I.POIZOT-MARTIN**, J.A. GASTAUT**, C.PENOT RAGON* 

*Pharmacie CHU Sainte Marguerite MARSEILLE **CISIH Sud CHU Sainte Marguerite 

MARSEILLE 

Objectives: To assess the compliance of patients undertaking highly active antiretroviral 

(ARV) therapy, based on an anonym self-questionnaire, in relationship with their therapy. 

Methods: Within CISIH (Centre d'Information et de Soins de l'Immunodéficience Humaine) 

of Sainte-Marguerite Hospital in Marseille, the Pharmacy department has an advanced 

delivery unit of antiretroviral therapy, allowing a preferential contact with the patients cared 

for in this center. Patients were proposed to answer a self-evaluation questionnaire during 

one month in October 2005. 

The questionnaire was composed by eight items: number of ARV drugs (one drug is 

considered as a brandname either it contains one, two or three molecules); quantity of 

pills; frequency of daily dose; management of drugs necessiting a cold storage; impact of 

adverse effects on patient adhesion to his treatment; information given to the patient 

towards his therapy. Apart the auto-evaluation, the patient was free to express his feelings 

towards his medical situation. 

Results: Among the 350 patients receiving their medications in the unit during October 

2005, 150 (43%) answered the questionnaire. We differenciated four patient compliance 

categories : 48% never forgot a dose (grade 1), 36% forgot a dose less than one time a 

week (grade 2), 9% forgot one dose a week (grade 3) and 7% more than one dose a week 

(grade 4). 

It can be correlated to the non-observance : 36% of grade 4 have to take between 6 and 

10 pills a day against 19% for the grade 1. Curiously, patients less observant are those 

taking less drugs : grade 4 have a maximum of 3 kinds compared with higher quantity 

(maximum 6) in the other categories, that could be explained by the increase of 

adherence with persistence and aggravation of symptoms. 

55% of grade 4 have adverse effects versus 30% in the grade 1. There are : gastrointestinal 

troubles, weariness, lipodystrophy, headache, muscular cramps the most 

frequently formulated by 1/3 of patients whatever the grade of compliance. 

Concerning drugs with a necessary cold storage, 100% of grade 4 declare that this 

obligation is a real daily problem, furthermore in occasionnal situation like business trip. 

Only 19 of the 150 patients (12,7%) declared being bad-informed about the therapy in a 

global way, what is a positive point for medical center staff, but they included 45% of the 

grade 4. 

Finally, to the item " free appreciation about your therapy ", great majority of people 

interviewed were optimistic, most of them still waiting for " a dose a day " and especially 

for the vaccine. 

Conclusions: Adherence impact is not always directly related to the number of drugs 

composing the therapy, but is more correlated to the number of daily pills, to cold storage 

constraint and patient's feeling of bad or lacking information. These data are the sensitive 

points on which all medical and pharmaceutical staff must improve their actions. 


PP 4.12 

Significant modification of administrative re-imbursement facilities of all lipid-lowering 

drugs in Italy. No consideration of HIV-infected patients with HAART-related 

dyslipidemia, who loss their right to a re-imbursed access to statins, fibrates, and 

omega-3 derivatives 



Introduction 

The significant HAART-prompted advances achieved in the management of HIV disease 

are at risk to be frustrated by the modified re-imbursement modalities of all lipid-lowering 

drugs (LLD) available in Italy. The remarkably increased life expectancy attained thanks to 

HAART, is borne by significant risks to develop a diet- and exercise-uncontrolled 

hypercholesterolemia and/or hypertriglyceridemia, often concomitant with insulin 

resistance and visceral adiposity, factors which strongly predispose to cardiovascular 

events and stroke. 


The novel prescribing rules of LLD based on a computer-generated score, were matched 

with the present situation of around 1,000 HIV-infected patients (p) treated with HAART, in 

order to assess the frequency and type of dyslipidemia, and the estimated rate of need of 

LLD prescriptions. 

Results 

The rate of hypertrigyceridemia and hypercholesterolemia exceeded 28% and 19% of p 

respectively, while around 22% of p had a mixed dyslipidemia. Over 200 p were currently 

treated with statins and/or fibrates,with the eventual adjunct of omega-3 fatty 

polyunsaturated acids (PUFA). When applying the risk score proposed for the general 

population, less than 10% of these p reached the threshold of a above 20% risk of a major 

vascular event in the next decade (due to the proportionally lower mean age, the 

absence of familial dyslipidemia, diabetes mellitus, elevated systolic pressure, and 

anti-hypertension therapy, compared with the general population), while only very few p 

needed a secondary prophylaxis, due to a prior, major cardiovascular or cerebrovascular 

accident. As a result, more than 90% of HIV-infected p presently treated with LLD due to 

present antiretroviral therapy recommendations have lost all rights to LLD re-imbursement 

in Italy, and are at serious risk to give up LLD due to not sustainable linked costs. 

POSTERS 

Conclusions 

The recent dispositions of the Italian Health Care System absolutely ignore the situation 

of HIV-infected p, who are exposed to a frequent, severe, drug-induced dyslipidemia, and 

an elevated major vascular risk despite their lower mean age, and the lack of multiple 

generic risk factors. At mid-term, the majority of HAART-induced benefits might be 

blunted by the sudden lack of LLD re-imbursement, which is estimated to regard the 

majority of treated HIV-infected p. A comparison with LLD re-imbursement facilities in 

other countries is also warranted, to draw some epidemiological and pharmacoeconomic 

elements suggesting a re-extension of re-imbursement facilities of these life-saving drugs 

to HIV-infected p. 


PP 4.13 

Treatment of Kaposi's sarcoma by Peginterferon alfa-2a 

Delassus JL., Malbec D., Ramanoelina J., Dallot A. 

Service de Médecine Interne CHI Robert Ballanger Boulevard Robert Ballanger 93602 

Aulnay sous Bois, France 

Objectives: 

Testing the efficacy of treatment of Kaposi's sarcoma (KS) by Peginterferon alfa-2a. 

Methods 

We report two cases of Kaposi's sarcoma in HIV infected patients without improvement on 

HAART and then treated by Peg Interferon (Peg-Inf) with a complete or partial remission. 

Results 

1 st case: A 42 years old man, Congolese, HIV infected was admitted because of a 

cutaneous and multi visceral (Lung, oesophagus, oral and ORL cavities) KS with HHV8 

serology positive. The CD4 cells were 198/mm 3 and viral load (VL) 467 000 copy/ml. We 

began HAART (3TC+AZT+LPV/r) and 3 courses of chemotherapy by adriamycin, 

bleomycin, vincristin, with a partial remission. Two years later, we observed a progression 

of cutaneous lesions and news locations (left cheek, eyelids, scalp, genital organs, lungs). 

CD4 cells were 203/mm3 and VL 52 copy/ml. A treatment by Peg-Inf alfa-2a 180µg/week 

by subcutaneous way was started with continuation of HAART. Six months later, we 

observed a complete remission of KS lesions. and we stopped Peg-Inf. One year later we 

established a maintenance of a complete remission of KS. The CD4 cells were 181/mm 3 

and VL

PP 4.14 

Immune markers of HIV disease progression are not modified by long-term statin 

administration, when considering HIV-infected dyslipidemic patients treated with a 

steadily, virologically effective HAART regimen. A prospective study, controlled 

versus fibrate administration, or a dietary/exercise program 



Introduction 

Statins as a whole, were recently hypothesized to act unfavorably on the immune system 

through an altered cytokine pattern and a Th1/Th2 imbalance,as shown in non-HIVinfected 

patients (p) [JAIDS 2005;39:503], while a small experience claimed a p

PP 4.15 

Pharmacokinetic Interaction Between the HIV protease inhibitors TMC114 and 

Indinavir, in the presence of low-dose ritonavir 

Sekar V, Lefebvre E, De Marez T, De Pauw M, De Paepe E, Vangeneugden T, 

Hoetelmans R 

Tibotec Inc., Yardley, United States of America, Tibotec Inc., Mechelen, Belgium 

Objectives 

The primary objective of this study was to investigate the potential for a pharmacokinetic 

interaction between TMC114, in combination with low-dose ritonavir (TMC114/r) and 

indinavir (IDV). The specific aims were to investigate: 1) the effect of steady-state 

concentrations of indinavir (IDV) on the steady-state pharmacokinetics of TMC114/r, and 

2) the effect of steady-state concentrations of TMC114/r on the steady-state 

pharmacokinetics of IDV. Secondary objectives were to assess the short-term safety and 

tolerability of coadministered TMC114/r and IDV. 

Methods 

Eighteen HIV-negative, healthy volunteers were enrolled in the study. Individuals received 

TMC114/r (400/100 mg b.i.d.), IDV/r (800/100 mg b.i.d.) and TMC114/r + IDV (400/100 mg 

b.i.d.+ 800 mg b.i.d.) on three separate sessions with a washout period of at least 7 days 

between regimens. In each session, study drugs were administered for 6 days with an 

additional morning dose on day 7. PK assessments were performed at steady-state after 

the morning dose on day 7 and pharmacokinetic parameters for TMC114, ritonavir and 

IDV were compared between treatments. Safety and tolerability were also assessed. 

Results 

Based on the least square means ratio (LSM) and 90% confidence intervals of LSM (CI), 

when TMC114/r and IDV were coadministered, TMC114 area under the curve (AUC12h), 

maximum plasma concentration (Cmax) and minimum plasma concentration (Cmin) 

increased by 24% (LSM 124%, CI 109-142%), 11% (LSM 111%, CI 98-126%) and 44% 

(LSM 144%, CI 113-182%), respectively, compared to when TMC114/r was administered 

alone. Upon coadministration, IDV AUC12h, Cmax and Cmin increased by 23% (LSM 

123%, CI 106-142%), 8% (LSM 108%, CI 95-122%) and 125% (LSAM 225%, 

CI 163-310%), respectively, compared to when IDV/r was administered alone. Systemic 

exposure to ritonavir was increased when IDV was added to treatment with TMC114/r, but 

was comparable between treatment with IDV/r and TMC114/IDV/r. Adverse events and lab 

abnormalities were more commonly reported during treatment phases with IDV. Oral 

paresthesia, nausea and headache were reported more frequently during TMC114/IDV/r 

treatment. The only treatment-emergent grade 3 abnormality occurring during a treatment 

including TMC114 was elevation of bilirubin, and this was observed during the 

combination phase, TMC114/IDV/r. No clinical symptoms were associated with this 

elevation. The co-administration of TMC114/IDV/RTV was generally safe and well 

tolerated. 

Conclusions 

From a pharmacokinetic perspective, TMC114/r may be co-administered with IDV; a dose 

adjustment of IDV to 600 mg b.i.d. may be warranted in case of intolerability. The efficacy 

and safety of the combination of TMC114/r and IDV has not been studied in HIV-1 

infected subjects 


PP 4.16 

Effects of demographic factors on trough lopinavir and ritonavir plasma 

concentrations in HIV- infected patients treated with Kaletra 

JM Poirier 1 , H Michelon 2 , X Lescure 3 , JL Meynard 4 , JB Guiard-Schmid 3 , O Zouai 1 , 

P Jaillon 1 , G Pialoux 3 , PM Girard 4 

1 

Department of Pharmacology, Saint-Antoine University Hospital, 2 Department of 

Pharmacy, Saint-Antoine Hospital, 3 Department of Infectious Diseases, Tenon Hospital, 

4 

Department of Infectious Diseases, Saint-Antoine Hospital, Paris, France. 

Background 

Contradictory data were reported on the influence of age and body weight on lopinavir 

(LPV) plasma concentrations. A large retrospective study was conducted to assess the 

effect of these factors and gender and race on trough (Cmin) LPV and ritonavir (RTV ) 

plasma concentrations. 

Methods 

LPV Cmin were measured at steady state 12±2h after the last drug intake only in patients 

treated by 400/100 mg bid LPV/RTV with two nucleoside/nucleotide transcriptase 

inhibitors. Patients with LPV Cmin < 1000 ng/mL were excluded from the study. Non 

parametric tests were used for statistical significance. 

Results 

Data from 332 patients were analyzed. Gender (94 female, 41%) and race (207 

caucasians, 62%) did not affect LPV Cmin. Spearman correlations showed a week effect 

of age on LPV Cmin (p=0.06) and a significant decrease in RTV Cmin (p

PP 4.17 

Human immunodeficiency virus type 1 (HIV-1) proviral load in patients in Structured 

Treatment Interruption 

Komninakis S.C.V.; Santos C.A.; Alkmim W.T; Teixeira C.C.; Sá-Filho D.; Diaz R.S. 

Laboratory of Retrovirology - Federal University of São Paulo, São Paulo City, Brazil. 

Objectives 

The persistence of the HIV-DNA into the host cells represent a large concern to 

eradication of infection. The ability to quantify the HIV proviral load in the peripheral blood 

mononuclear cells (PBMCs) could provide important informations about this reservoir and 

may be used for monitoring disease progression. We have developed a system for 

measuring HIV-1 proviral load in PBMCs of 18 patients for 12 weeks in STI. 

Methods 

Our system amplified a conserved region in HIV-1 pol gene and the intron 12 of human 

albumin gene. HIV-1 proviral load were obtained from 18 buffy coat samples collected between 

1999 and 2000 from subjects that participate of the STI for a period ranging from 0 

to 12 weeks (without treatment). Were constructed two standard curves to determine the 

HIV-1 proviral load and albumin gene (slope= -3,08, r2= 0,99, and slope= -3,62, r2 = 0,90, 

respectively). 

Results and Conclusions 

We compared the HIV-1 proviral load between 0 and 12 weeks and, in the 0 week was 

detected ranged between 30X10-2 and 92X10-2 provirus/total leucocytes whereas in the 

12 week this variation were 29X10-2 and 104X10-2. In our results evaluated the proviral 

load variation for each sample between 0 and 12 weeks, was observed a tendency to 

reduce in six samples and exhibited a clear tendency to increase in 12 samples 

(average= 3,77±23, confidence interval=95%). A statistical analysis of PBMCs HIV-1 

proviral and plasma RNA load of all 18 patients showed no correlation. Our system was 

able to quantify the HIV-1 proviral load per cellular genomes in retrospective samples. 

No correlation was found between HIV-1 proviral load and plasma RNA load. The proviral 

load evidenced a tendency to increase in some samples and may be used to monitoring 

STI studies. 


PP 4.18 

Rosuvastatin administration for protease inhibitor-related hyperlipidemia, with a 

predominant hypercholesterolemic component 

Leonardo Calza, Roberto Manfredi 


Introduction 

Lipid-lowering therapy is recommended to HIV-infected patients (p) when protease 

inhibitor (PI)-associated hyperlipidemia (often represented by a mixed form of 

hypercholesterolemia-hypertriglyceridemia), is severe or persists for a long time despite 

diet-physical exercise, but the choice of hypolipidemic drugs is often problematic due to 

pharmacological interactions, increased toxicity, and lack of comparative randomized 

trials. 


The aim of our prospective, open-label pilot study was to assess the efficacy and safety 

of the novel, potent statin rosuvastatin for the management of HIV-infected p receiving a 

PI-based anti-HIV therapy. Selection criteria included p with hypercholesterolemia 

persisting for six months or more. P were treated with rosuvastatin (10 mg/day) for 24 

weeks, when an interim analysis was performed. 

Results 

Until now, 25 p were enrolled and followed-up. At the end of the 24-week preliminary 

observation period, the median reduction of cholesterol-triglyceride levels versus median 

baseline values was 22.1% (range 14.2-32.1%) and 26.9.1% (range 17.8-37.1%), 

respectively (p

PP 4.19 

Much More Sure than 2 Years Ago: The CD4-Stabilizing Effect of 5 mg Prednisolone 

Daily in HIV-Patients without HAART 

Ulmer, Albrecht; Mueller, Markus; Frietsch, Bernhard 

HIV-practice 

Schwabstr. 26 - D-70197 Stuttgart Germany 

Objective 

The Isheid-conference in Toulon 2004 was the first international HIV-conference with an 

oral presentation about the low-dose-Prednisolone (pred)-data for HIV-patients. 

Meanwhile we have learned a lot, and it's necessary and thrilling to present the newest 

knowledge and developments. 

Methods 

We treated 81 therapy naïve patients with CD4 =300/µl (mean 576) for 0.5-13.5 years and 

168 pretreated patients for 0.5-5.9 years during therapy interruptions (STI) with 5 mg pred 

daily. CD4 profiles (absolute, % and ratio) viral load and clinical events were compared 

with those of all untreated control patients (therapy naïve n = 165, mean CD4 613/µl, 

pretreated n = 57). 

Results 

All evaluations show a CD4-advantage for the pred-treated patients, significantly in the 

therapy naïve patients, nearly significant in the pretreated patients. In therapy naïve 

patients, we observed no disadvantage. A few patients showed a development 

establishing hope that they'll never need any antiretrovirals, others years later. The risk of 

immundeficiency-related, mostly mild diseases is generally increased during STIs. With 

pred, we observed more OHL and oral candidiasis. Counting all events, we didn't find a 

difference between patients with and without pred, but the better CD4-profile with pred 

enabled us to conduct many STIs for years, saving antiretrovirals of more than 12 Mio 

Euro, only in our center. 

Conclusions 

The data is still monocentric, not randomized and not the result of an official study, but it 

is much more confirmed than 2 years ago: With pred, we observed better CD4-profiles 

and a notable prolongation of time without HAART. Two official studies have been 

arranged in Germany and Africa, meanwhile. 5 mg pred daily have nearly no long term 

side effects, are extremely inexpensive (3 Euro a year in developing countries) and 

easily available world-wide. 


PP 4.20 

Arising questions on a cost-effectiveness and pharmacoeconomic investigation 

focused on diagnosis, management and prevention of osteopenia and 

osteoporosis in the setting of HIV disease treated with HAART 



Introduction 

Osteopenia and/or osteoporosis are emerging untoward effects of HIV infection, 

especially when treated with HAART. The pathogenesis is multifactorial, involving all 

classes of anti-HIV drugs, although protease inhibitor use, overall HAART duration, and 

the male sex, seem related to a greater risk. 

Epidemiological and clinical data 

In an ongoing study at our Centre where over 1,000 HIV-infected patients (p) are followed, 

bone mineral density was assessed in lumbar spine and femural head, by a dual energy 

X-ray absorptiometry (DEXA) exam, in order to estimate the prevalence of osteopenia 

and/or osteoporosis. In a preliminary screening of around 100 p, the frequency of 

osteopenia and osteoporosis (based on lumbar T-score) was around 38% and around 

10%, respectively. An increased risk was found in p treated with protease inhibitors 

versus those receiving non-nucleoside reverse transcriptase inhibitors or triple 

nucleoside/nucleotide analogue combinations. 

Discussion and Future Insights 

Prospective studies of extensive p samples are needed, to elucidate the epidemiology, 

pathogenesis,clinical issues, and evolution of HIV-associated bone metabolism 

abnormalities. When planning strategies for their early diagnosis, prevention, and 

management, also cost-effectiveness issues should be taken into careful consideration, 

since no pharmacoeconomic data still exist in this setting. Although severe consequences 

(e.g. pathological fractures, prosthetic implants), are expected to be infrequent, their 

consequences in terms of length and intensity of hospitalization,related costs, and 

especially severe consequences on the patient's quality of life, play a notable role. 

Anyway,the most reliable diagnostic procedure (DEXA) has affordable costs (around Euro 

43.40 for a total-body scan which also offers a body composition assessment), as well as 

the first-line drugs for osteopenia, e.g. supplementation with calcium (Euro 5-6.5/month), 

and vitamin D (Euro 7/month). These costs cannot be compared with the costs of a 

standard care of an asymptomatic HAART-treated p (Euro 471 to Euro 774/month), and 

the immunological, virological, laboratory, and clinical controls made at least quarterly in 

these patients. Like postmenopausal osteopenia and osteoporosis (burdened by a 

greater risk of bone mass anomalies), also HIV disease should be investigated from 

multiple cost-effectiveness points of view, to establish which p are the preferred 

candidates for a DEXA screening, when this examination is more useful during HIV 

disease course and therapy, when the exam should be repeated, and when and how to 

intervene pharmacologically, to prevent serious and potentially invalidating complications. 

POSTERS 


PP 4.21 

No evidence of reduced viro-immunological response in HIV+ patients previously 

naïve to antiretroviral treatment carrying non B or B HIV-1 subtypes 

Maria Cristina Uccelli 1 , Franco Gargiulo 2 , Carlo Torti 1 , Giuseppe Lapadula 1 , Silvia 

Costarelli 1 , Giuliana Cologni 1 , Filippo Castelnuovo 3 , Giuseppe Paraninfo 3 , Nino Manca 2 , 

Giampiero Carosi 1 

1 

Institute for Infectious and Tropical Diseases, University of Brescia, Brescia, Italy; 

2 

Institute for Microbiology, University of Brescia, Brescia, Italy; 

3 

Spedali Civili di Brescia, Brescia, Italy 

Objectives 

To assess viro-immunological response after first line HAART in patients harbouring 

subtype B (HIV-B) or different from B (HIV-nB) HIV-1 isolates. 

Methods 

All consecutive patients naïve to antiretroviral drugs who started a protease inibitor (PI) or 

non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART were selected, 

provided that a genotypic resistance testing was performed before commencement of 

therapy. Subtypes non-B were identified using www.hiv.lanl.gov/content/hivb/basic_blast/basic_blast.htm. 

Univariate and multivariate logistic regression analyses 

were performed with an as-treated approach using the following outcomes: HIV-RNA 

PP 4.22 

The incidence and reasons of the premature giving up of abacavir in HIV patients 

within 2 months following the treatment setting-up 

FOUCHER N.,AZARD J.,PERTUSA MC.,BERNARD N.,LACOSTE D.,MORLAT P., 

POMETAN JP. 

Service pharmacie et Service de Médecine interne et maladies infectieuses, hôpital Saint 

André, Bordeaux, France 

Background 

Abacavir is a nucleoside reverse-transcriptase inhibitor (NRTI) whose most characteristic 

adverse effect is an hypersensibility reaction (HSR) which usually occurs in the first 6 

weeks of treatment. This adverse effect causes the final adoption of the treatment with 

formal prohibition of a new prescription of this molecule. 

Objectives 

Determine the incidence of abacavir giving up within 2 months following its setting-up and 

analyse their reasons. Identify the number of abacavir giving up due to true HSR 

according to its definition criteria. 

Methods 

This retrospective study concerns 628 patients who had begun a treatment by abacavir 

between January 1998 and January 2006. This cohort is extracted from the Pharmatip 

software, used in the pharmacy of the Saint Andre hospital (CHU Bordeaux), which allows 

a monthly delivery of the ARV drugs. We selected the patients who gave up abacavir and 

who received a substitute treatment delivered by the pharmacy during at least one year. 

Thus, the files of 32 patients were studied to evaluate the causes of abacavir giving up. 

We retained the usual criteria of HSR's definition: presence of at least 2 signs among 

fever, cutaneous eruption, gastrointestinal symptoms, lethargy, malaise and respiratory 

symptoms, in coherence with the time of appearance of the symptoms, their aggravation 

during the treatment and their fast resolution at abacavir giving up. 

Results 

Of the 628 patients exposed to abacavir, 32 patients (5,1%) gave up abacavir in the first 

2 months and their substitute treatment could be followed by the pharmacy. Among these 

32 patients, 10 patients presented a true HSR, 15 did not develop HSR and 7 cases were 

doubtful due to the lack of precision in the file. We obtained an incidence of 5,1% for 

abacavir giving up due to the appearance of adverse effects but the incidence of the true 

HSR was only 1,6%. The signs observed in the cases of undeniable HSR confirm the 

definition of an abacavir HSR: 80% presented fever, 60% lethargy or feeling of faintness, 

60% gastrointestinal symptoms and 50% a cutaneous eruption. Among the 10 true HSR, 

3 patients had a treatment by INNTI associated, 2 patients among the 15 non HSR cases 

and 2 among the doubtful cases. 

POSTERS 

Conclusion 

This work made it possible to identify the patients having develop an abacavir HSR and 

to announce them to whole the medical community of Bordeaux. This study, in clinical 

practice, shows that true HSR is not the majority cause of abacavir treatment giving up. 

Very often, the least suspicion of a HSR leads to the treatment giving up. These 

excessive abacavir giving up do not allow certain patients to profit from this molecule for 

the rest of their life. 


PP 4.23 

The increased liver toxicity of nevirapine over efavirenz does not depend on the 

female gender, and an initially elevated CD4+ lymphocyte count, in a single-centre 

comparative study with efavirenz conducted on 720 overall patients 



Introduction. Some observations prompted to our attention a potentially increased 

hepatotoxicy of nevirapine, with significant rise among women with a baseline CD4+ 

lymphocyte count >250 cells/µL. Aim of our study is to conduct an analysis from our 

database of patients treated prospectically with either nevirapine or efavirenz, to better 

define this claimed association. Patients and Methods. Among over 1,000 patients treated 

with HAART for >12 months, the hepatotoxicity pattern of both NNRTI was assessed 

according to three different backgrounds: antiretroviral-naïve patients starting a 

NNRTI-based regimen; a large spectrum of patients experienced with two to ten 

therapeutic lines (while remaining NNRTI-naïve); and finally subjects who added for the 

first time a NNRTI only on late rescue therapies containing four drugs or more (and always 

including protease inhibitors). Results. Three hundred and 34 patients treated with 

nevirapine were compared with 386 individuals taking efavirenz in our survey, by a 12-30 

months multivariate analysis of liver enzyme abnormalities, together with a varied 

spectrum of epidemiological, clinical, and laboratory parameters. Instead of normal 

laboratory levels, we referred to the values found at treatment start. The two study groups 

were comparable as to epidemiological-clinical features and HIV virology, while a lower 

CD4+ count was found in subjects starting efavirenz (p

PP 4.24 

Early aplasia resulting from interaction between antiretroviral therapy and 

vinblastine in a patient with HIV-associated Hodgkin's disease 

1 

A. Makinson, 2 N. Martelli, 2 H. Peyrière, 1 Ch Turriere, 1 J Reynes 

1 

Infectious Diseases Department, Gui de Chauliac Hospital, University Hospital of 

Montpellier 2 Medical Pharmacology Department, Lapeyronie Hospital, University Hospital 

of Montpellier, France. 

Background 

Pharmacokinetic interactions between anti-neoplastic drugs and highly active 

antiretroviral therapy (HAART), especially protease inhibitors, have been recently 

described. Data regarding drug to drug interactions and recommendations of dose 

modifications or drug monitoring are scarce. Methods: We report a case of early severe 

aplasia following anti-neoplastic drug administration with vinblastine for a HIV-associated 

Hodgkin lymphoma in a patient treated by boosted protease inhibitor based salvage 

HAART. Follow-up and management of this case are discussed. 

Results 

A 36-year-old HIV-infected man was treated with lamivudine, tenofovir, lopinavir-ritonavir 

and enfuvirtide, with a viral load and T CD4 lymphocyte count in January 2006 

respectively measured at 188 copies/ml and 164/mm 3 . Other daily treatments included 

clindamycin (600mg), pyrimethamine (50mg) for secondary prevention of cerebral 

toxoplasmosis, monthly pentamidine aerosols for prevention of pneumocystosis and 

spironolactone (25mg), perindopril (2mg) for a HIV related cardiomyopathy. Stage IVB 

Hodgkin lymphoma was diagnosed in februrary 2006 and treated according to the ABVD 

protocol: vinblastine (6mg/m 2 ), doxorubicine (25mg/m 2 ), bleomycine (10mg/m 2 ), 

dacarbazine (375mg/m 2 ) and prednisolone (40mg/m 2 ). Severe febrile aplasia was 

diagnosed 6 days after administration with neutrophil nadir of 0/mm 3 . The following cure 

was realised with reduced doses of vinblastine (4mg/m2) and administration of 

dexrazoxane (500mg/m 2 ), but febrile aplasia also ensued with neutrophil nadir of 87/mm 3 . 

POSTERS 

Conclusion: In this case report, inhibition of cytochrome P4503A4 by ritonavir probably 

contributed to severe aplasia, as this isoenzyme is the major metabolic pathway of 

vinblastine. Inhibition of P-glycoprotein efflux pump by ritonavir may represent an 

additional mechanism. Patients with HAART receiving anticancer drugs should be 

closely monitored and dosage reductions should be considered, especially if treated with 

boosted protease inhibitors and vinblastine. However, recommendations regarding 

dosage modifications or drug monitoring are lacking and pharmacological studies should 

be performed 


PP 4.25 

Rapid Oral Desensitization to Abacavir in Case of Probable Hypersensitivity 

Ulmer, Albrecht; Mueller, Markus; Frietsch, Bernhard 

HIV-practice - Schwabstr. 26 - D-70197 Stuttgart, Germany 

Objective 

Symptoms of Abacavir (ABC) hypersensitivity syndrom (HSS) are not always clear and 

sure. Initially in cases of doubt, later on, in probable cases, we tried to transfer a method 

of rapid oral desensitization to trimethoprim-sulfamethoxazole, as published in 1995, to 

ABC. The manufacturing company strictly recommends to discontinue taking ABC in such 

cases. But then a precious substance is lost forever. 

Methods 

Of 360 patients treated with ABC, 15 (4,4%, 9 men, 6 women) reported HSS-probable 

symptoms within the first 19 (mean 6,1) days: 10 x fever or feeling of having influenza, 

1 x myalgia and arthralgia, 7 x nausea, 3 x stomach ache, 3 x diarrhoea, 5 x exanthema 

(4x mild, 1 x fotodocumented) 4 x pharyngitis, 1 x trembling and 1 x dyspnoea. Mean CD4 

was 420.1 (20 - 1030)/µl. All patients had antiretroviral pretreatment, and 14 of them, 

parallel to the start with ABC, a prescription of 5 mg prednisolone daily. 

In 5 cases, ABC was stopped at once. In 10 patients, we performed a sequence of 

dilutions, beginning with 1 teaspoon of a solution of one tablet in 200ml water. The 

dosage was doubled every 12 hours if the symptoms remained gone. The original 

dosage was reached again within a few days, not later than after 1 week. Prednisolone 

dose was raised to 10mg daily in the first days. Patients were asked to come daily for 

checks. 

Results 

HSS-symptoms disappeared in 7 of the 10 patients within the first day and didn't reappear. 

In all of these 7 patients ABC was tolerated well afterwards and in 6 patients effective 

(continuous reduction of viral load (VL)

PP 4.26 

Cell-cycle independent antiretroviral therapy: combination of nevirapine, 

emtricitabine, and tenofovir 

Charles Davis, Anthony Amoroso, Bruce Gilliam, Derek Spencer, Becky Boyce, 

Shannon Berg, Joyelle Dominique, Sandy Zaremba, Robert Redfield 

Institute of Human Virology Baltimore, Maryland, USA 

Background 

Published data demonstrates differential anti-viral activity of specific reverse transcriptase 

(RT) inhibitors in resting and activated PBMCs, however, Abacavir, Tenofovir (TDF), 

Emtricitabine (FTC), and NNRTIs inhibit RT independent of cell cycle. We hypothesized a 

cell cycle independent RT based regimen would be potent and demonstrate durable viral 

suppression. 

Methods 

This is an open-labeled, 96 week clinical trial evaluating the efficacy of TDF 300 mg qd, 

FTC 200 mg qd, and Nevirapine (NVP) 200 mg b.i.d. Entry criteria included: >18 y.o. with 

established HIV; ARV-naive; CD4 count of 5,000 c/mL. 

Results 

Thirty (70% male, 97% African American) volunteers have enrolled to date. The mean 

HIV-1 RNA and CD4 count at baseline (BL) were 5.15 log10 (47% with viral loads 

> 100,000) and 149 cells/mL, respectively. The mean decline in RNA at Week 2 was 2.09 

log10. Week 24 analysis (ITT and OT) showed 73% and 96% < 400 c/mL, and 70% and 

91% < 50 c/mL. The mean increase in CD4 count from BL was 109 cells/mL (OT). Twenty 

two subjects have completed 48 weeks: 16/22 (73%) and 16/16 (100%) had HIV-1 RNA 

< 400 c/mL and 15/22 (68%) and 15/16 (94%) < 50 c/mL, ITT and OT, respectively; the 

mean increase in CD4 cell count was 186 cells/mL. A transient self-limited mild rash not 

requiring therapy interruption occurred in 4 subjects. Two volunteers developed grade 

4 LFT elevation and 1 volunteer developed grade 4 neutropenia: all resolved with 

discontinuation of the ARVs. 

POSTERS 

Conclusion 

The combination of TDF, FTC, and NVP appears very potent, safe, and well tolerated, 

even at high viral loads. This study provides evidence-based data to support the use of 

TDF, FTC and NVP in patients with CD4 cell counts < 250, including in resource-limited 

settings, and warrants further evaluation. 


PP 5.1 

Rational design of HCV antigens to contend with diversity and optimize T cell 

reactivity 

Yusim K. 1 , Fischer W. 1 , Perkins S. 1 , Frahm N. 2 , Brander C. 2 , Bhattacharya T. 1 , Theiler J. 1 , 

Allen T. 2 , Lauer G. 2 , Kuiken C. 1 , Korber B. 1 

1 

T-Division, Los Alamos Natl. Laboratory, Los Alamos, 

2 

AIDS Research Center, Harvard Medical School, Boston, United States 

Objectives 

Designing an effective vaccine for HIV and HCV is a many-faceted challenge. Potent 

vaccines are needed, with optimized vectors, immunization protocols, and adjuvants. 

Given enormous sequence diversity of these two viruses, vaccine optimization strategies 

will not suffice without the parallel development of strategies that stimulate protection 

against the diverse spectrum of circulating viruses. For a CTL based vaccine it means that 

cross-recognition between vaccine strains and circulating strains should be maximized. 

Prototype natural sequences are being considered for both viruses, but diversity 

coverage could be significantly improved using optimized synthetic sequences. 

Methods 

Since CTL epitopes are usually 9 amino acid long fragments, a computational 

optimization method maximizing the population coverage of 9-mers was developed. 

Polyvalent vaccine antigens containing sets of "mosaic" proteins assembled from 

9-mer fragments of natural sequences are designed in such a way that for each 

overlapping 9-mer the frequency of each variant appearing in the input sequence set is 

evaluated. Importantly, high-frequency overlapping 9-mers are often not compatible, so 

the relative benefit of each amino acid variant is assessed in combination with other 

nearby variants. The most beneficial variants are assembled in a mosaic protein in the 

order they appear in the natural sequences. Every single 9 amino acid long sequence 

fragment in these mosaic proteins exists in a natural sequence, and so mosaic proteins 

resemble natural proteins. The method could be used for any pathogen and so far has 

been applied to HIV and HCV. 

Results 

High coverage of circulating proteins is feasible with a small number of mosaic proteins. 

For example, in an alignment of 165 sequences representing genotype 1 variation in 

NS3-NS5 HCV protein region, 87% of potential epitopes (9-mers) are matched perfectly 

within a set of four mosaic proteins, and 98% have at least an 8/9 aa match. In contrast, 

with a single genotype 1 natural strain, only up to 65% of potential epitopes could be 

matched perfectly and only up to 80% could have 8/9 aa match. 

Conclusion 

HCV genotype 1 mosaic protein sets provide diversity coverage comparable to hundreds 

of separate peptides. By weaving together fragments of proteins derived from natural 

sequences, this coverage is achieved with a small number of proteins, tractable the 

design of antigens for T cell responses screening and for vaccine design. A vaccine 

stimulating polyclonal responses to multiple epitope variants may be beneficial as it could 

enable responses to a broader range of circulating variants and it could also prime the 

immune system against common escape mutants. 


PP 5.2 

Detection of HIV/HCV Co-infection Markers in Blood and Saliva 

Alexey I. Mazus, Alexander Y. Olshanskiy, Irina A. Simonova, Alexander A. Goliusov, 

Yuri Martinov 

Moscow Centre for HIV/AIDS Prevention and Treatment, 5-15 8th Sokolinoy Gory Str., 

Moscow 105275, Russia; Moscow State University of Medicine and Dentistry, 20/1 

Delegatskaya Str., 103473, Moscow, Russia 

We investigated matched plasma and saliva samples from 34 HIV-infected individuals. 22 

of these patients were co-infected with HCV. 13 patients were on HAART. 

We detected 1) the viral load (RNA HIV-1, RNA HCV) by PCR; 2) HIV-1,2 antibodies by 

ELISA and Western blot; 3) antibodies to core, NS3, NS4, NS5 antigens HCV by ELISA. 

We found correlation between HIV viral load in plasma and saliva. 18% of plasma samples 

showed the viral load < 400 copies/ml, while for the remaining 82 % (28 patients) it 

ranged from 526 to 215000 copies/ml. The HIV viral load was < 400 copies/ml in 13 

saliva samples (42%), and ranged from 403 to 263,000 copies/ml in the other 18 samples 

(58%). 

The correlation coefficient shows direct correlation between HIV viral load in blood and 

saliva (r = +0.3925±0.14 t=2.78. p

PP 5.3 

Immune restoration levels under highly active antiretroviral regimen, in patients 

co-infected with HIV and HCV 

Roberto Manfredi 


Introduction 

A recent metanalysis conducted by M. F. Miller [CID 2005;41:713] claimed a significantly 

reduced immune recovery in HCV-HIV patients (p) undergoing HAART, as measured by a 

simple mean absolute CD4+ lymphocyte difference. 

Methods and Results 

On our opinion, he study design, data analysis, statistics, and main clinical inferences are 

seriously influenced by multiple drawbacks. Of the only eight trials extracted from a 

database of 152 (5.3%), only 5 are prospective in structure, and p enrollment covered a 

very long 1992-2002 period, with only four of eight studies limited to naïve p. The 

statististical assessments appear forced to obtain greater p samples, but failed to report 

the cumulative mean CD4+ levels±SD or ±SE of the two p groups of 3,317 and 1,579 p 

respectively, while a broad dissertation exists about the mean 30 CD4+ cell decrease (with 

more detail, from 151.6 vs 113.8 cells/µL), without considering that these figures cannot 

prescind from (ungiven) baseline CD4+ lymphocyte counts. The sample size strongly 

influences statistical comparisons, and even minimal differences may be magnified, by 

artificially increasing study samples. When making the exercise to double the p samples 

of the Miller study, we obtain a significant p=.048 difference, still when the absolute 

difference between groups is 2.6 CD4+ cells/µL. Technically, the absolute CD4+ cell count 

(regardless of total lymphocyes, cell subset percentages, and so on), is influenced by 

multiple variables: circannual-circadian courses, gender, ethnicity, transitory viralinflammatory 

processes, HCV genotype, and assay limitations, which make a 5% 

difference absolutely negligible. Multiple adjunctive variables should be added when 

HIV-HCV-co-infected p undergoing HAART are assessed, so that a mean difference of 

around 30 absolute CD4+ cells/µL is only academically (but not clinically) relevant. Finally, 

a difference limited to around 30 (C.I.23.5-43.4) CD4+ cells/µL, cannot play whatsoever 

role on hard end-points of HAART treatment. 

Conclusions 

Relevant questions should be addressed by "prospective cohort studies…that account 

for…degree of liver disease,duration of HIV-HCV infection,baseline HIV load, and different 

treatment regimens", as recognized by Miller itself. However, we cannot absolutely agree 

with the conclusive Authors' statements: "This meta-analysis shows that p with HIV-HCV 

coinfection do…have less immune reconstitution, as determined by CD4+ cell count after 

48 weeks of HAART, than…p with HCV infection alone". Moreover,we believe that the 

Authors failed to add significantly to the knowledge of the multifactorial HIV-HCV-HAART 

interferences. Indeed, this study overestimates a minor laboratory figure, enforced by a 

misleading and a forced use of statistical assessments. 


PP 5.4 

The Impact of Hepatitis on Health-related Quality of Life and Medical Expenditures 

in the United States 

Sullivan, PW Ghushchyan, V 

University of Colorado School of Pharmacy Pharmaceutical Outcomes Research Program 

Denver, Colorado, USA 

Objective 

Acute and chronic liver disease caused by viral hepatitis results in significant morbidity 

and mortality in the United States. The purpose of the current study was to examine the 

impact of hepatitis on health-related quality of life (HRQL), comorbidity and medical 

expenditures in the United States. 

Research Design and Methods 

We used a nationally representative survey of the United States population with detailed 

information on medical conditions, HRQL, utilization of health care resources and medical 

expenditures. Data from 2000-2002 containing 64,261 individuals were used. The current 

study examined the following outcomes for individuals with hepatitis compared to those 

without: 1) SF-12 physical function scores (PCS-12), 2) SF-12 mental function scores 

(MCS-12), 3) the medical cost associated with viral hepatitis for each individual, 4) the 

national cost in the US, and 5) the cost for all major payers. 

Results 

Individuals with hepatitis had significantly lower mean PCS-12 (40 vs. 49) and MCS-12 

(45 vs. 51) scores; higher median annual medical expenditures per individual ($4224 vs. 

$597); higher median annual prescription drug expenditures ($822 vs. $41); and a 

greater number of reported chronic conditions (4.8 vs. 1.5). Results are also provided by 

payer type (Medicare, Medicaid, Private insurance and Self). 

Conclusions 

The current study provides evidence of the significant negative impact of hepatitis on 

HRQL and medical expenditures in the United States. 

POSTERS 


PP 5.5 

Fulminant Candida albicans peritonitis and ascites in a HIV-HCV co-infected patient, 

possibly prompted by a prolonged self-administration of nimesulide 



Introduction 

The mortality rate of HIV-infected patients (p) with concurrent liver disease is steadily 

increasing. 

Case Report 

An exceedingly rare case of Candida albicans fulminant peritonitis and ascites in a p with 

HIV-HCV-coinfection, but no prior history of liver cirrhosis, which was possibly related to 

exaggerated self-administered nimesulide,is reported. A 46-year-old p with HIV infection 

recognized since 14 years received isolated lamivudine-stavudine therapy since six years 

with a favorable laboratory response, as expressed by a plasma viremia of 480 HIV-RNA 

copies/mL, and a CD4+ lymphocyte count of 428 cells/µL. Neither liver biopsy nor 

specific treatment were performed for a concurrent stable HCV infection. Two months 

before admission, our p suffered from a shoulder fracture, and uncontrolled nimesulide 

self-medication was performed during six consecutive weeks. A rapidly worsening ascites 

and oliguria led to hospital admission. Slightly increased serum ALT, amylase, and 

bilirubin were detected, but a rapidly increasing ascites and diffuse edema occurred, 

paracentesis, and diuretic-albumin administration failed to improve the clinical picture, and 

the worsening ascites and anuria evolved into hyperacute kidney failure. One day later our 

p deceased, and necropsy studies showed a diffuse polyvisceritis and hepatitis with 

abundant ascites, in absence of kidney and urinary tract abnormalities, and liver cirrhosis. 

After patient's death, multiple ascites cultures yielded isolated Candida albicans. 

Conclusions 

HIV-infected p have increased risks of liver toxicity. Non-steroideal anti-inflammatory 

drugs (NSAID) are implicated in severe, sometimes lethal hepatotoxicity. The exceedingly 

rapid-severe evolution towards a Candida-infected ascites associated with refractory 

anuria, in absence of decompensated cirrhosis, acute hepatotoxicity, and kidney 

involvement at autopsy, was never observed after NSAID/nimesulide use. Animal models 

showed a NSAID-induced increased enteric vascular permeability causing infectious 

peritonitis. In conclusion, clinicians who face p with chronic hepatitis but no 

decompensated cirrhosis, should remind that NSAID may act on liver-bowel function, and 

could prompt a liver-kidney damage, possibly complicated with infectious ascites. 


PP 5.6 

Extrahepatic manifestations of HCV; An experience from endemic country 

Alaa sabry, Mahmoud Elbaz, Mohemed Sobh. 

Mansoura urology and Nephrology Center, Egypt 

Background 

Hepatitis C virus (HCV) infection in Egypt has reached an epidemic proportion and is 

associated with many extra hepatic manifestations; Glomerulonephritis (GN) is one of the 

most consequences of HCV infection often resulting in end stage renal disease in some 

cases. Detection of viral genome or particles within the kidney biopsies from HCVinfected 

patients has proven to be difficult. Histological characterization of renal lesions 

still represents a major challenge. The aim of our work was to describe the histological 

pattern of HCV-associated nephropathy. 

Methods 

Fifty Patients out of 233 presented to Mansoura Urology and Nephrology clinic with 

manifestations of glomerular disease were screened for HCV antibodies by a 3 rd 

generation ELISA test. Those tested positive for HCV antibodies were confirmed by PCR 

for HCV-RNA and subjected to more detailed clinical, biochemical and histological study. 

Kidney biopsies and in appropriate cases liver biopsies were examined by LM and 

electron microscopy (EM). 

Results 

Histological study of renal biopsies revealed membranoproliferative (MPGN) type 1 to be 

the most common lesion encountered (54%), followed by focal segmental 

glomerulosclerosis (FSGS) (24%), mesangioproliferative GN (18%), membranous 

nephropathy (MN) (4%) in that order. EM examinations of renal biopsies were successful 

in identifying HCV like particles in frozen renal tissue. 

Conclusion 

HCV-associated glomerulopathy is a distinct category of glomerulonephritis. Results of LM 

showed some peculiar features. In addition, we were successful in location and detection 

of HCV particles in renal tissues by EM. 

POSTERS 


PP 5.7 

Chronic hepatitic C-prompted peglylated interferon (IFN) plus ribavirin therapy and 

re-activated, acute, serious lung tuberculosis 



Introduction 

Tuberculosis may be reactivated also after many years through a primary, silent, and 

unknown tubercular infection, when immunodeficiency (often jatrogenic in origin), or other 

risk factors (e.g. cancer, cachexia), become apparent. Post-primary tuberculosis episodes 

were described also decades after a primary Mycobacterium tuberculosis infection, in 

patients (p) who show apparently limited radiographic signs at chest radiographic and 

computerized tomography (TC) examination. Some grade of immunodeficiency may also 

depend on the administration of associated IFN-ribavirin for an underlying chronic HCV 

hepatitis, as expressed by the frequent emerging of leukopenia-neutropenia, and am 

altered cytokine network. 

Case report 

In a p aged over 50 years with negative medical history of tuberculosis, an occasional 

chest X-ray showed fibrous-calcified infiltrates at upper right lobe. After 11 years, due to a 

progressive chronic HCV hepatitis, pegylated IFN plus ribavirin were started with good 

tolerability for seven months, until a sudden occurrence of cough and hemopthisis 

associated with a pulmonary lesion highly suggestive of tuberculosis became apparent, in 

the same area where some reliquates of a primary tuberculosis were demonstrated 11 

years before. A high-resolution CT examination pointed out two different excavated 

infiltrates. Both direct microscropy and culture of sputum-BAL proved positive for M. 

tuberculosis (susceptible to all tested compounds), while a positive of Mantoux reaction 

also became evident.An absolute lymphopenia (nadir 966 cells/µL), prompted a T-cell 

subset study, which showed an imbalance of the CD4+/CD8+ lymphocyte ratio (30/45%), 

and an absolute CD4+ lymphocyte count of 290 cells/µL. Notwithstanding five 

consecutive weeks of isoniazide, ethambutol, rifampicin and pyrazinamide administration, 

sputum examination remained positive, thus confirming the role of immunodeficiency in 

prompting a difficult-to-treat tuberculosis. 

Discussion 

Waiting for human experimental data, two animal models demontrated that an increased 

release of immunosuppressive cytokines (IL-10, TGF-beta), may prompt a reactivation of 

tuberculosis, while a maintained T-cell competence enhances the latency of tuberculosis. 

From a clinical point of view, although a few cases of non-infectious lung involvement, 

interstitial pneumonia, and bronchiolitis obliterans were described during IFN therapy 

administered to transplant p, no episodes of reactivated tuberculosis were reported. 

Although our disease association seems unique, the expected increase of therapeutic use 

of IFN and potent agents for the management of chronic hepatitis or other diseases, might 

support the reactivation of latent tuberculosis. A careful medical history, Mantoux reaction, 

and a chest X-ray, are mandatory before starting IFN therapy. In fact,the jatrogenic 

immunosuppression related to IFN and ribavirin may go beyond the expected 

leukopenia-lymphopenia, and also act against the quantitative and functional role of CD4+ 

lymphocytes. This last circumstance may play a key role in the reactivation of 

tuberculosis, when a latency is present. 


PP 5.8 

Management of Chronic hepatitis C with Pegylated Interferon and Ribavirin in a 

Prison Setting 

Sergio Sabbatani, Ruggero Giuliani, Roberto Manfredi 


Introduction 

The elevated frequency of chronic HCV infection found among prison inmates, and the 

availability of improved pharmacological cure for this potentially life-threatening disorder, 

make the investigations conducted in this somewhat neglected area very promising, since 

only a few, open-label experiences are recorded until now. 

Patients, Methods, and Results 

In a serological survey conducted in the metropolitan prison of Bologna (Italy), HCV seroprevalence 

was recognised over 31% in the year 2003, so that a pilot feasibility study 

based on treatment with associated pegylated interferon plus ribavirin was initiated, after 

a careful counselling carried out by joined health care personnel of the correctional 

facility and Infectious Diseases consultants. Thirty-nine patients were enrolled, and 

despite expected drop-outs due to difficulty in maintaining the same counselling pressure 

during time, and the particularly unfavorable climatic conditions occurred in Summer 2003, 

a sustained virological response was obtained in 8 out of 21 patients who remained 

evaluable after the first three month of follow-up (38.1%), although we have to take into 

account that a relevant percentage of subjects (66.7%) were selected for therapy due to 

their favorable HCV genotypes (types 2 and 3). 

Conclusions 

Our preliminary experience shows that an intrinsecally complicated therapy such as the 

administation of pegylated interferon plus ribavirin, may be conducted with a 

proportionally elevated success rate also in a very unfavorable and unconfortable context, 

such as a prison, where only enforced counselling, active participation of internal health 

care operators, and patient's willingness maintaing an elevated level of co-operation and 

adherence, can overcome most of structural and relational difficulties typical of this 

difficult setting. 

POSTERS 


PP 5.9 

Chronic HBV infection associated with opisthorchiasis: efficacy of antiviral therapy 

Kulagina Olga, Kulagina Kristina 

Department of Infectious Diseases, Kemerovo State Medical Academy, Kemerovo, 

Russia. Student, Kemerovo State Medical Academy,Kemerovo, Russia. 

Background 

Chronic infection caused by Opisthorchis felineus (O.f.) is relatively common in Western 

Syberia (Russia). Moreover, 14% of the chronic HBV infections are associated with 

opisthorchiasis in this region. Opisthorchiasis might cause marked immunosuppression 

and lead to the antiviral treatment failure. In our study we assessed efficacy of 

antiretroviral therapy in patients with chronic HBV/O.f. co-infection. 

Methods 

In total 70 patients experiencing chronic HBV infection were involved into the study. Thirty 

five patients with chronic HBV/O.f. co-infection constituted the case group, while 35 

patients without opisthorchiasis served as a control. In both groups at baseline HBV 

infection had signs of replication stage and moderate activity. All patients were prescribed 

lamivudine, 100 mg orally daily for 48 weeks. Treatment outcomes were assessed by 

blood testing for HBV DNA at 6 and 12 months after 48 weeks of therapy. Outcome 

variables were measured by proportions and Pearson chi-square test was applied to 

assess their differences between groups. 

Results 

A sustained virologic response (HBV/DNA negative at 12 months after 48 weeks of 

therapy with lamivudine) was achieved in 35 (50%) patients. In the case group fewer 

patients had a sustained virologic response than those in the control group, however, 

these differences were not statistically significant (respectively 14 (40%) and 21 (60%), 

p=0.09). A transitory virologic response (HBV/DNA negative at 6 months, but HBV/DNA 

positive at 12 months after 48 weeks of therapy) was observed in 18 (25.7%) patients. A 

response rate of 20% was seen in patients from the case group and of 31.4% in patients 

served as a control (p=0.27). 

Conclusions 

We recorded a negative trend of antiviral treatment outcomes in patients with chronic 

HBV/O.f. co-infection. The problem needs to be studied more profoundly; absence of 

statistically significant differences between groups might be due to small number of our 

observations 


PP 6.1 

Air Evacuation of patients with High Infectious Disease under Biosafety 

Containment 

Marco Lastilla*, Roberto Biselli**, Ferdinando Arganese**, Manfredo Di Stefano**, Ottavio 

Sarlo** 

Medical Law Institute of Italian Air Force, Rome, Viale P. Gobetti 2, 00185 

** Logistic Command Medical Service of Italian Air Force, Rome, Viale P. Gobetti, 2A 

00185 

We know with increased global travel, military contingency operations in tropical 

environments and potential use of biological weapons by bioterrorist may place many 

people at risk for potentially lethal contagious disease.Diagnosis and treatment of such 

infections would be expedited by evacuating a limited number of patients to a facility with 

containment laboratories with Biosafety Level 4. To safely evacuate such patients by 

military aircraft and minimize the risk for transmission to air crews, caregivers, and 

civilians, the Medical Service Italian of Italian Air Force has istituited an aeromedical 

isolation unit in Pratica di Mare Airport close Rome. 

After special training, this rapid response team, which has long airlift capability designed 

to evacuate and manage patients under high-level containment, also offers a portable 

containment laboratory, limited environmental decontamination, and specialized 

consultative expertise. Our capability is of two Aircraft Transit isolators and two Stretcher 

transit isolators with a medical team included specialist in infectious disease. This 

presentation showes also examines technical aspects of the team's equipment, training, 

capabilities, and deployments. The design and construction of the isolators are similar to 

that of transparent flexible PVC isolators adapted both for in-patient and transport use. 

The HEPA filters are certified to remove 99.7% of all particles 0.3 [micro]m to 3 [micro]m 

in diameter. 

Isolators have been used to treat in-patients with suspected Ebola, Lassa, and Marburg 

hemorrhagic fevers, SARS and suspected biological casualties. The utility and safety of 

these isolators for inpatient care have been questioned, and their use in hospitals is not 

recommended. However, transport isolators, the only available technical means of 

reliably maintaining airborne isolation in a military transport aircraft, have been 

successfully used for the aeromedical evacuation of patients with suspected Ebola fever 

and suspected and proven Lassa fever. 

The air and stretcher isolators feature transparent PVC envelopes suspended from metal 

frames by detachable plastic rings. Both envelopes include gloved sleeves, transfer and 

docking ports for patient entry, and transfer and supply ports for introducing supplies. 

Electrical current is supplied by rechargeable batteries or the aircraft electrical system. 

Both isolators can be equipped with portable oxygen tanks, intravenous fluids and tubing, 

medication, and portable defibrillators. 

We describe our experience transporting a patient with lung tuberculosis MDR with some 

aspects of an operative mission of the Aeromedical isolation team of Italian Air Force 

made their first transport using isolator systems. 

The patient, sputum positive for BK under medical treatment, was transferred by aircraft 

C 130J from Alghero Airport, in Sardinia Island, to Linate Airport in Milan to be recovered 

in Sondalo Hospital specialising in tuberculosis. 

The flying time was of one hour against 20 hours estimated by ambulance car and boat. 

Tuberculosis multidrug resistant is an infectious disease transmitted by air way more 

severe for the high resistance at medical treatment. 

Under biosafety containment the patient with transmissible infectious disease can be 

transported without any risk to healthcare personnel. 

POSTERS 


PP 6.2 

Broadly protective immunity against influenza A using a synthetic vaccine 

D. E. Anderson 1 , A. Ogrel 2 , M. Ghorbani 2 , C. Soare 2 , K. Gee 2 , J. V. Torres 2 , 

F. Diaz-Mitoma 2 ; 

1 

Variation Biotechnologies, Inc., Gatineau, PQ, CANADA, 

2 

Children's Hospital of Eastern Ontario, Ottawa, ON, CANADA. 

Background 

While we currently possess efficacious vaccines against influenza, they must be 

reformulated each year due to antigenic variation in the surface proteins of the virus, a 

lengthy process that takes more than 6 months. We report a completely synthetic 

approach to the production of a universal influenza vaccine that can be accomplished in 

6 weeks. 

Objectives 

To design and synthesze a universal influenza vaccine candidate. 

Methods 

Using analysis of the crystal structure of influenza hemagglutinin (HA) protein, we have 

designed 4 linear peptide epitopes that mimic discontinuous epitopes on the HA protein 

surface. Using bioinformatics software that analyzes the antigenic variation of HA proteins 

from thousands of human influenza isolates, we have further designed degenerative 

peptide cocktails based on these epitopes, called Discosites, that represent the antigenic 

variation of HA within these epitopes. 

Results 

Using sera obtained from B6 mice immunized with these Discosites in the presence of 

Alum, we demonstrate that this candidate influenza vaccine elicits antibodies with 

hemagglutination inhibition (HI) titers (1:320) against divergent subtypes/strains of 

influenza including two H3N2 strains (A/HK/1/68 and A/Fugi/411/02) and an H1N1 strain 

(A/NC/20/1999). The titers elicited are greater than those induced with a currently 

licensed human influenza vaccine. Challenge studies using pathogenic H3N2 

(A/HK/1/68-MA20c) in B6 mice (n=8/group) demonstrate that the vaccine induced 

protection greater than that induced with adjuvant controls or a commercial vaccine. 

Conclusions 

Collectively, these data suggest a fundamentally new approach to influenza vaccine 

development that results in faster vaccine production and broader protection than current 

influenza vaccines. This approach may be of particular value to the development of a 

pandemic influenza vaccine. 


PP 6.3 

Imported Chikungunya related chronic poly-arthritis : 2 cases 

Rapp c, Ficko C, imbert P, Barruet R, Debord T 

department of infectious and tropical diseases Military Hospital Bégin, 

94163 Saint-Mandé, France 

Over the past year, the Comoros and the Reunion Island have been successively 

affected by a severe epidemic of Chikungunya virus infections. In addition to the rare 

severe neurological forms described in the Reunion Island, the possibility of chronic 

poly-arthritis deserves to be known in France. 

Case1: In May 2005, a 49 year old Comorian woman presented with an acute febrile 

poly-arthritis (hands, left hip and ankles), 7 days after her return from a month stay in 

Moroni. 

We observed a limitation of the left hip and an edema of the ankles and of the distal 

interphalangeal joints. The CRP was 16 mg/L (N < 1). The radiographs were normal. The 

Chikungunya serology (IgM) was positive. After an initial response to Non-Steroidal 

Anti-Inflammatory treatment, the evolution was marked with chronic pain and morning 

stiffness.The search for inflammatory poly-arthritis was negative (ANA, anti-dsDNA, 

rheumatoid factors). The disabling symptomatology improved in the seventh month after 

many NSAI treatments. 

Case 2: In December 2005, a 69 year old woman presented with a congestive chronic 

poly-arthritis (wrists, ankles, shoulders and hips) evolving for more than 2 months after a 

Chikungunya infection contracted in the Reunion Island and serologically confirmed. The 

diagnosis of chronic inflammatory rheumatism was ruled out, the outcome was slowly 

favourable. 

The scale of the current epidemic is the opportunity to remind that the articular tropism of 

the Chikungunya virus can mimic inflammatory rheumatism in its initial stage, particularly 

in women over 40 years old. Spared hips in the rare retrospective series can also be 

affected.This viral poly-arthritis, described initially in Africa and easily diagnosed in an 

epidemic stage should henceforth be considered in front of a sporadic case of 

poly-arthritis in travellers . 

POSTERS 


PP 6.4 

Chikungunya arthritis sequelae: Molecular homology between Lyme arthritis 

Borrelia Burgdorferi, LFA-1a and Chikungunya virus gp1 

Tran MKG 1*, Caprani A.* 

*Association "POSITIFS",Paris, 1 Université Paris V 

Introduction 

Chikungunya virus is an arthropod-borne spread by the mosquito Aedes Albopictus. 

Chikungunya virus infection in the French La Réunion island is an epidemics of 

catastrophic amplitude: About 160,000 patients were already infected, with 77 deaths 

(mostly among elderly patients, but also young infants). The disease can be transmitted 

from pregnant mother to infant. Invalidating after effects such as chronic painful 

arthralgias/arthritis (wrists, hands, ankles, knees) many months after are the main clinical 

feature, hence the Swahili name Chikungunya: "that which bends up". No specific 

anti-viral treatment is known, except those discovered in cell cultures (interferon-alpha, 

ribavirine, glycyrrhizine,…). A vaccine was started in the 1980s in U.S.A. but stopped. 

Objective 

No molecular biology research until now has been done on this virus, so we tried to 

discover why rheumatologic features were dominating the clinical picture of the chronic 

form in a subset of patients. 

Method 

We reasoned by analogy with a well known affection with arthritis after effects: Lyme 

disease, induced by a spirochete (Borrelia Burgdorferi) and with a known HLA-DR4 

rheumatologic susceptibility marker (the same as for rheumatoid arthritis); in this case, 

there exists a molecular mimicry between LFA-1 α and Borrelia Burgdorferii Outer 

surface protein (OspA). We decided to screen all the alphavirus inducing arthralgias/ 

arthritis with LFA-1. The amino acid sequences were aligned to find perfect matches 

(molecular mimicry or homologies). 

Results 

They were exactly as expected. Borrelia Burgdorferi OspA sequence SYVLEGT was 

identical to Chikungunya virus gp1 SY-LEGT excepted one gap. This nucleus alignment 

allows to align correctly all the arthritis-inducing arbovirus family (Chickungunya, Ross 

River, Sindbis, Barmah Forest, Mayaro, etc…) (McGill PE, 1995) with LFA-1 α : 

Borrelia Burgdorferii OspA 

Chikungunya virus gp1 

LFA-1 α human 

LFA-1 α mouse 

Ross River virus 

Sindbis virus 

Barmah Forest virus 

Mayaro virus 

SYVLEGT 

SY- LEGT- R 

KIYVIEGTSKQ 

R 

HSY -LEGT-R 

(Y,V)EGT-RD 

SY- LEGT-K 

SY- MEGT-K 


Conclusion 

By analogy with Lyme arthritis, Chikungunya virus arthritis sequellae occur by a 

mechanism of molecular mimicry between LFA-1 α and a viral protein, here Chikungunya 

virus gp1, hence inducing a deleterious auto-immune immune response. In Lyme 

arthritis, such event occurs only in susceptible patients, those having the HLA-DR4 

rheumatologic marker. Thus, it could be interesting to search this marker in Chikungunya 

infected patients to predict if they will suffer in the future of arthralgia sequellae. 

The second lesson is to treat very precociously the patient (like in Lyme disease) with 

available drugs (pegylated interferon a, ribavirine excepted in pregnancy) before the 

irreversible phase II, when the arthralgia sequellae are definitively installed. This epitope 

can serve as a protective hapten in a therapeutic purpose. A vaccine developed for Lyme 

arthritis has been designed which mutated the auto-immune epitope while conserving the 

protective sequence (Willett T.A., 2004): This could be also a good model for designing a 

vaccine against Chikungunya arthritis. 

Discoveries in Chikungunya virus research represents also progress in treatment and 

management of other rheumatologic alphaviruses such as Ross River virus in Australia, 

etc... 

POSTERS 


PP 6.5 

Experimental determination of the infectivity of avian influenza virus aerosols 

A.S. Safatov, A.N. Sergeev, S.A. Kiselev, E.A. Stavskij, L.N. Shishkina, E.I. Ryabchikova, 

M.O. Skarnovich, A.A. Sergeev, M.A. Smetannikova, A.P. Agafonov, V.A. Petrishchenko, 

V.M Generalov, G.A. Buryak, I.G. Drozdov 

Federal State Research Institution State Research Center of Virology and Biotechnology 

"Vector", Koltsovo, Novosibirsk region, Russia. 

According to the WHO data, 212 human cases of H5N1 avian influenza (including 116 

lethal ones) have been reported since 1997 in different countries by the beginning of April 

2006. Human diseases occur through the contact with infected birds while 

human-to-human transmission of the virus has not been recorded. As the aerosol way of 

human-to-human transmission of influenza is the main one, we investigated aerosol 

characteristics of avian influenza virus ?/Chicken/Suzdalka/Nov-11/2005 (?5N1) isolated 

in Novosibirsk region and its infectivity for chickens. 

At the first stage, the comparison of survival rates of avian influenza virus and human 

influenza virus (A/Aichi/2/68 strain ?3N2 subtype) was performed via aerosolizing an 

aqueous-glycerol solution of virus-containing suspensions using a Collison nebulizer. 

It was found out that 3.6 ± 1.8% of virions preserved their infectivity in the dispersion of 

human influenza virus at the temperature of 21÷23?? and the relative humidity of 

approximately 30%. For avian influenza virus, this quantity makes up only 1.0 ± 0.9% 

under the same conditions. Electron microscopic analysis of the virions morphology 

performed with the negative contrasting method revealed the "staining" of the core of 

avian influenza virion as compared with human influenza virions, which is indicative of the 

destruction of membranes. Peplomers, usually existing on the surface of human 

influenza virions, were not found either. 

To determine the chickens' sensitivity to the studied strain of avian influenza virus, the 

birds were challenged intravenously or intranasally. Intranasal infection is equivalent to 

that with a coarsely dispersed aerosol, but allows the infecting dose to be controlled more 

precisely. It was found out that, on average, the dose of 1 EID50 caused 50% death rate 

at intravenous infection of birds. This indicates that LD50 values coincide both for an ECE 

and an adult bird. At intranasal infection of chickens, LD50 value is estimated at 500 - 

1000 EID50. Thus, infection of birds with a coarsely dispersed aerosol of avian influenza 

virus is not the most efficient way of the infection transmission as it happens in the 

process of human-to-human transmission of human influenza virus. 

The carried out experiments showed that, obviously, the aerosol way of the infection 

transmission is not the main one at bird-to-bird and bird-to-human transmission of avian 

influenza. The analysis of literature sources show that for birds the main way of the virus 

transmission is fecal-oral, and for man it is, probably, an analogue of the former as a result 

of nonobservance of the personal hygiene rules. 


PP 6.6 

Tick-borne-lymphadenopathy (TIBOLA) : an emerging infectious disease in France 

Rapp C, Ficko C,Imbert P,Barruet R, Debord T 

Department of infectious and tropical diseases Military Hospital Bégin, 94163 Saint- 

Mandé, France 

Rickettsia slovaca is an emerging rickettsiosis described for the first time in France in 

1997. Its underrated clinical presentation must be distinguished from Lyme Borreliosis. 

A 73 year old woman, without past record, presented in June 2005 with a scalp lesion 

associated with cervical lymph nodes. Fifteen days previously, she had a tick bite while 

she was in the Nîmes region. Lyme disease diagnosis was suspected in the presence of 

a scalp erythema halo, headaches and arthralgias. A treatment by amoxicilline had been 

initiated. The examination showed a scalp eschar, a localized alopecia and tender 

occipital adenopathies. The blood count was normal and the ALAT were twice the normal 

level. A 200 mg/day doxycycline cure was administered during 5 days. The R. slovaca 

serology was not contributory but the Western Blot (serum) showed R. slovaca specific 

antibodies. The dead tick PCR analysis confirmed the presence of R. slovaca, the cell 

culture was negative. The outcome was marked by a residual alopecia at the bite site. 

This new TIBOLA case report due to R. slovaca confirms the emergence of this infection 

which is transmitted to man by the Dermacentor genus ticks. The inoculation eschar which 

is sometimes associated with an erythema halo must not be confused with the Lyme 

disease's erythema chronicum migrans better known by practitioners. As it is suggested 

in our case, the scalp localization and lymphadenopathy are suggestive signs. Diagnosis 

confirmation relies on techniques carried out on skin biopsies from the inoculation eschar 

particularly and also on the serum or the conserved tick. These techniques are only 

available in the Marseille Rickettsial diseases National Research Center. 

POSTERS 


PP 6.7 

Emerging Arboviruses in Turin Province 

Agostino Pugliese and Tiziana Beltramo 

Dep. of Medical and Surgical Sciences, Section of Clinical Microbiology, University of 

Turin, Italy 

Emergence and re-emergence of Arboviruses is a raising problem in different areas of the 

world, and also in Europe. For example Dengue virus has been described in some 

Mediterranean regions, West Nile (WNV) in East Europe, in France, Spain and Portugal, 

Toscana virus (TOSV) in Mediterranean basin and Tick borne encephalitis (TBE) in 

Central and North-Eastern Europe. Our study group firstly investigated arbovirosis s 

eroprevalence in Turin Province in at high risk population for arthropod's bite, like as 

hunters and breeders, and in low risk persons. A total of 400 subjects were evaluated with 

specific ELISA tests. TBE virus showed a seroprevalence of 5.7% in at risk population, 

and 1.7 % in low risk one, TOSV ranging from 2-3.7% in all cases, Dengue not more than 

2% and WNW always showed negative results. In particular it is interesting to notice that 

high risk tick's bite population presented 62.5±32.8 of anti-TBE IgG mean titres vs 23±10.3 

of low risk subjects ( p = 0.001). In conclusion our study suggests that only TBE virus 

seems to be significantly present in Turin Province. Instead Dengue is presumably exotic 

agent, TOSV is almost absent and WNV is quite absent. 


PP 6.8 

Re-Emerging Tuberculosis. Are There Significant Correlations with HIV Infection 

and Other Risk Factors, between residents and immigrants? 



Introduction 

Tuberculosis (T) is borne by increasing morbidity-mortality rates, due to changes of the 

epidemiologic scenario, and diffusion of resistant strains. The recent, profound 

modifications occurred among predisposing factors (increase mean patient [p] age, 

concurrent diseases, iatrogenic immunosuppression, alcoholism, drug use, migration, and 

HIV pandemic), played a key role in this process. 

Methods 

Among the 128 consecutive p hospitalized due to T since 1996, we compared the 77 p 

from Italy with the 51 immigrants from extra-European countries, in relation of a number 

of variables and risk factors, including HIV serostatus. 

Results 

Compared with immigrants, Italian p had a higher frequency of HIV-AIDS (32.4%; p

PP 6.9 

Ocular LOA-LOA Infection in an Italian restricted Man 

Roberto Ranieri 1 , Lidia Gazzola 1 , Laura Paganardi 2 , Claudia Santambrogio 2 , 

Rosa Maria Anania 2 , Teresa Bini 1 , Antonella d'Arminio Monforte 1 , Rodolfo Casati 2 , 

Marco Bongiovanni 1 

1 

Clinic of Infectious Diseases, San Paolo Hospital, University of Milan; 

2 

Unit of Internal Medicine V, San Paolo Hospital 

Background 

The ocular localization of parasites of Loa-Loa species is an unusual finding in developed 

countries and, to date, only few cases have been reported in literature. 

Case report 

A thirty-six years old Caucasian Italian man who lived from 1992 to 1999 in a rural area of 

Angola, was admitted to our Clinic for abdominal discomfort. In Angola, he had several 

admissions in hospitals due to yellow fever and recurrent episodes of malaria. When the 

patient returned to Italy, he was restricted and he was still restricted when he firstly came 

to our observation. At hospital admission, routine blood examinations showed HCV-Ab 

positivity and elevated IgE levels (1303 UI/mL). Chest radiography, colonoscopy, 

ultrasound abdominal scan, stools examinations for bacteria, parasites and Mycobacteria 

were all negative; white blood cells were in the normal range as was the peripheral 

eosinophil count. The abdominal discomfort recovered in few days; the day when discharge 

was scheduled, the patient referred irritation and discomfort in his left eye and 

contemporarily he saw something wiggling in it. The ward clinicians saw a thin, undulating 

worm under the conjunctiva; however, the ophthalmologist failed to find anything but focal 

choroiditis signs in the patient's eye. These symptoms recovered after few hours, and later 

on the patient did not notice anything of abnormal. Though the patient did not report 

history of skin swellings or other compatible symptoms with a previous parasitic infection, 

the findings of choroiditis signs, the long period and the setting in a rural African country, 

led to a suspected diagnosis of worm infection by Loa Loa species. All the blood smears 

performed to search microfilaria, collected at adequate times, were negative; on the 

contrary, serum anti-filarial antibodies levels were 310 µg/mL. A treatment with 

prednisone and diethylcarbamazine was then scheduled; however, such treatment was 

started only 45 days after the diagnosis because of diethylcarbamazine was not available 

in Italy and was extremely difficult to find in other European Countries. The treatment was 

well tolerated and the patient did not refer anymore ocular symptoms in the next visits. 

Conclusions 

The diagnosis of tropical diseases is becoming quite frequent in developed countries due 

to travels and/or immigration. Clinicians should always be aware of these diseases when 

evaluating subjects who lived in developing countries for a long period. Therefore, any 

patient with unclassifiable eye affection should also be investigated for those rare 

pathogens. Once the diagnosis of microfilaria infection is made, it has to be stressed the 

problematic availability of the first choice's drug in the European scenario. 


PP 6.10 

Complicated Listeria monocytogenes central nervous system (CNS) infection in an 

otherwise healthy host. Favorable response to linezolid, notwithstanding early 

myelotoxicity 

Roberto Manfredi, Sergio Sabbatani, Ginevra Marinacci 

Infectious Diseases, University of Bologna, Bologna, Italy 

Introduction. CNS listeriosis outside of pregnancy,neonatal period, and immunodeficiency, 

is uncommon. Meningitis and especially CNS abscess lead to major diagnostic-therapeutic 

concerns. Anecdotal episodes of L.monocytogenes CNS infection were reported from 

immunocompetent patients, where diagnosis is hampered by a low clinical suspicion. 

Case report. A 50-year-old male with negligible history and no obvious L.monocytogenes 

exposure was hospitalized owing to worsening dizziness. A brain CT scan and EEG 

detected aspecific abnormalities. Shortly, hyperpyrexia, headache, and vomiting became 

evident, with temporal-spatial confusion and head stiffness, thus prompting a lumbar 

puncture. CSF studies showed elevated albumin (217 mg/dL), very low glucose levels (4 

mg/dL), and 256 leukocytes/µL (60% neutrophils), so that high-dose ceftriaxonechloramphenicol 

were started,with dexametazone-mannitole adjuvant therapy. At the 4 th 

day,altered mentation and a peripheral facial nerve palsy occurred,and L. monocytogenes 

was identified from the CSF, so that chemotherapy was changed towards high-dose (12 

g/day) ampicillin and 240 mg/day gentamicin, according to the in vitro susceptibility 

testing. Persistingly severe clinical-neurological conditions, and altered CSF assay, 

prompted a novel shift of antimicrobial therapy (to rifampicin-cotrimoxazole), 10 days after 

hospitalization. Eight days later, a spasmodic torticollis appeared, associated with an left 

dysmetria-hypostenia,anisochoria and nistagmus,and difficulty to swallow. A head-neck 

MRI showed small, hyperintense roundish focal lesions localized at the left posteriorlateral 

portion of the medulla oblongata (Figure 1). The hypointense internal signal, and 

the hyperintense peripheral ring of the multiple lesions involving the pons Varolii,the left 

cerebellar hemisphere and bulb, were interpreted as multiple bacterial abscesses. 

Another change of antimicrobials involved i.v. linezolid (1,200 mg/day), and meropenem 

(6 g/day). Although after 6 days of combined linezolid-meropenem treatment an evident 

anemia required a RBC transfusion,at the 14th day of therapy the CSF examination 

remarkably improved,while fever and other systemic signs-symptoms disappeared. 

A persisting anemia prompted another RBC transfusion,and made necessary the 

replacement of linezolid with i.v. cotrimoxazole after 21 days. Seven days later our patient 

was discharged with a completely normal CSF,and an almost complete recovery of 

neurological deficits. Within a 12-month follow-up,no further episodes of anemia occurred 

after linezolid suspension,and control MRIs performed confirmed the complete 

disappearance of Listeria abscesses. Discussion. Our report of a L. monocytogenes 

meningitis complicated by multiple subtentorial abscesses (including rare localizations at 

cerebellum,bulb,and pons Varolii), had an evolving and cumbersome clinical presentation 

and course. A Listeria cerebellar abscess, and multiple brain stem abscesses seem to 

have only one literature equivalent in an otherwise healthy patient, whose diagnosis was 

made by surgery [Addas BM, Saudi Med J 2002;23:226]. Despite the demonstrated in 

vitro activity of multiple agents,repeated chemotherapy changes became necessary, until 

the meropenem-linezolid combination, which was introduced at the appearance of the 

most severe neurological complications, and proved very effective,although affected by 

relapsing anemia probably attributable to linezolid,and requiring transfusions. 

A meningitis and/or multiple CNS L.monocytogenes localizations should be not 

overlooked in otherwise healthy individuals without any relevant exposure to this 

pathogen,due to the need of a prompt recognition and an effective treatment,to avoid a 

possible life-threatening course. Linezolid,thanks to its excellent pharmacokinetic 

properties,elevated CSF-brain penetration,and activity against a broad spectrum of CNS 

pathogens (including the intracellular L.monocytogenes),is expected to become a key 

antimicrobial compound,waiting for randomized controlled trials in this challenging setting. 

POSTERS 


PP 6.11 

Prevalence of Carriers of Methicillin Resistance St aphylococcusaureus (MRSA) in 

100 Staff of Shahid Beheshti Hospital of Kashan (Iran) 

Khorshidi, A . Shajari, Gh . Hosseini Nejad ,A 

Khorshidi, A . Shajari, Gh . Hosseini Nejad ,A 

Kashan University of Medical Sciences,Kashan(Iran) 

Background 

Staphylococcus aureus is recognized as one of the most important bacterial pathogens 

seriously contributing to the problem of hospital infections all over the world. The source 

of infection is nasal carrier hospital personnel. Determination of antibiotic resistance 

pattern of isolated strains is essential for treatment of carrier. 

Objective 

The aim of this study was access the incidence of methicillin resistant S.aureus (MRSA) 

carriage in the Shahid Beheshti University Hospital, Kashan (Iran). 


To find prevalence of MRSA carrier, A prospective survey was conducted over 100 

personnel in Shahid Beheshti Hospital of Kashan, from March 2001 to Sep 2002, total 

specimens were taken from the anterior nares of staff, were cultured on the selective 

media, isolates were identified based on coagulase and conventional biochemical 

reactions according in Standard Method. 

All staphylococcus isolates were screened for methicillin resistance by in oculation of 

Muller-Hinton agar supplemented with salt and oxacillin 6 µg/ml, according to National 

Committee for Clinical Laboratory Standards (NCCLS) guidelines, other tested antibiotics 

included amoxicillin (20 µg), ciprofloxacin (5 µg), penicillin (10 units), gentamycin (10 µg), 

rifampin (30 µg) vancomycin (30 µg), then the results were presented by descriptive 

analysis. 

Results 

The results showed (12%) of Staphylococcal isolates were coagulase positive, of the total 

Staphylococcus aureus, 7 (58.3%) were resistant to methicillin. 

Conclusion 

Resistance pattern of Staphylococcus aureus to various antibiotics, especially methicillin 

is towards increasing trend, it seems the prevalence of MRSA clonisation in the staff of 

University Hospitale of Kashan (Iran) is increasing. 

Keywords 

Antibiotics, Carriage, Nasal, Staphylococcus aureus, Methicillin - Resistant 

Staphylococcus aureus 


PP 6.12 

Severe, extensive, and difficult-to-eradicate Strongylodies stercoralis infection 

probably supported by an underlying Sjogren syndrome requiring long-term steroid 

treatment 



Introduction 

In the majority of otherwise healthy patients (p), strongyloidiasis (S) remains 

underestimated: only when some primary-secondary immunodeficiency occurs, S may 

involve multiple organs, outside the more obvious gut localization, towards disseminated 

and/or relapsing manifestations. 

Case report 

A female p who suffered from Sjogren syndrome treated since over 20 years with cyclic 

oral steroids, due to dyspeptic signs and symptoms underwent an endoscopy which 

detected a histopathology-confirmed gastroduodenal S. After a three-day albendazole a 

repeated endoscopy-histology showed a persisting S, so that a further albendazole cycle 

was administered, but two subsequent controls (performed four and ten months after), 

demonstrated the persistence of S. stercoralis infection. Upon Hospital admission (nine 

months later), our p suffered from weight loss and anemia. Stool, sputum, and urine 

search for S. sterocoralis tested negative, as well as HIV and HTLV-1 serology, and 

tumoral markers. A two-day ivermectine treatment at 12 g/day, preceded a three-day 

albendazole course performed the subsequent week, and a three-day mebendazole one 

week later. Repeated endoscopy was performed one and two months after discharge, 

confirming a sustained cure of S, associated with improved general conditions and a body 

weight regain. During the entire evaluation and treatment period, the concurrent steroid 

therapy (prednisone, at 25 mg/day), was deemed necessary for the concurrent Sjogren 

disease, and was therefore never interrupted. 

POSTERS 

Discussion 

S is endemic in tropical and subtropical regions, where severe associations were 

demonstrated in HTLV-1-infected p. In developed countries, p with a broad spectrum of 

underlying diseases, or receiving immunosuppressive drugs, may suffer from S 

refractory to first-line therapy, due the frequency of re-infestation. Although anecdotal 

reports regarded p with chronic disorders and collagen vascular disease, no p with 

Sjogren syndrome was reported to date. The described report is therefore an unique 

association of a difficult-to treat S occurring in a p with a steroid-controlled Sjogren 

syndrome. Since controlled trials and definite recommendations are lacking, either 

albendazole, thiabendazole, ivermectin, or mebendazole at different dosages and 

schedules were used, while the management of relapses lacks of evidence-based 

guidelines. Clinicians should also consider that S is expected to increase its frequency, 

based on environmental changes (increased temperatureand humidity), just in countries 

where an increasing number of p become at risk for opportunism in the meantime. 


PP 6.13 

Evaluation of the Prevalence of Urinary Tract Infection and Determination of 

Antibiotic Sensitivity and Resistance Pattern in the Hospitalized and Out patients 

referred to Shahid Beheshti Hospital of Kashan -Iran 

Khorshidi. A, Shajari. Gh, Saffari. M, Mossavi. Gh 

Kashan University of Medical Sciences, School of Medicine, Department of 

Microbiology , Kashan (Esfahan(Iran) 

Background & Objective 

Urinary tract infections are the most common infection that are reported on the basis of 

available statistics between 30-50 % of people and even until 80 % of women. UTI is the 

most major reason for weakens, mortality and morbidity in present medical world. 

Regarding to inaccessibility to accurate of prevalence of UTI and no information of the 

bacterial agents and antibiotics pattern of them in recent years in the University Hospital 

of Kashan , This study was performed in the hospitalized and outpatients that referred to 

Shahid Beheshti hospital of Kashan(Iran) in the first six months of 2005 

Materials and Methods: 

A descriptive study was performed over 4037 patients referred to Shahid Beheshti 

Hospital Laboratory in the first six months of 2005. 

Urine samples were cultured and identified according in Standard Method. Then 

susceptibelity test was performed by disc diffusion method (kirby-Bauer). The results and 

demographic characteristic were registered, and were presented by descriptive analysis. 

Results 

From 334 patients with positive urine culture, 220 (65.9%) were female and 114 were 

male. most of the urinary tract infections were in the age of 20-40 (46.1%). the most 

common pathogen were E coli (53.9%) and Klebsiella (24.9%). E. coli showed the most 

sensitivity to amikacin (89.3), ceftizoxim (76.1%). ceftriaxon (71.9%), ciprofloxacin 

(64.7%). The most sensitivity in Klebsiela to amikacin was (76.4), cefotaxim (75%), 

ciprofloxacin (71%). The most sensitivity in Eterococcuse to vancomycin was (84.6%), 

amikacin (66.7%) and the most antibiotic sensitivity in Coagulase Negative 

Staphilococcus to vancomycin was (92.8%), amikasin (63.7%). 

Conclusion 

Research showed that the most common pathogen of UTI was E choli with a high 

sensitivity to ciprofloxacin, ceftriaxon and amikacin. On the contrary a high resistance to 

ampicilin, amoxicilin and co-trimoxazole. Therefore it is recommended that before 

advising each kind of antibiotic, antibiogram test be performed and effective antibiotic be 

determined and then treatment procedure be done on the basis of results of antibiogram 

and clinical symptoms of patients. 


PP 6.14 

Primary Cytomegalovirus (CMV) Infection with Symptomatic Course in Otherwise 

Healthy Adults: Increased Incidence, or Improved Laboratory Facilities? 



Introduction 

The increased availability of serological and biomolecular assays for the diagnosis of 

acute CMV infection, allowed us to include these assays in the workup of fever of 

unknown origin (FUO) in immunocompetent adults. 

Patients and methods 

A retrospective study of patients (p) diagnosed with primary CMV infection during 

assessments for a FUO, was performed at our reference centre. 

Results 

One hundred and 11 p aged 13-42 years (44 males, and 67 females) were assessed for 

a FUO since the year 2001. The diagnostic workup also included CMV serology with 

IgG-IgM search, while pp65 antigenemia and CMV viremia were carried out in selected p. 

Of 111 p, 16 (14.4%) had a positive CMV IgM assay, confirmed in six p by biomolecular 

testing and antigen search. An altered leukocyte count and differential were always 

present, while T-lymphocyte subsets showed a transient reversal of CD4+/CD8+ ratio, 

with a reduced percentage and absolute number of CD4+ lymphocytes (250-580 cells/µL), 

and an expanded CD8+ phenotype. Concurrent signs-symptoms included fever in all p, 

associated with a mononucleosis-like syndrome in 13 cases. A moderate (2-4-fold) rise of 

serum transaminases was found in 12 episodes, in association with an ultrasonographyconfirmed 

hepatosplenomegaly In three p, the predominant signs-symptoms were fever, 

asthenia, fatigue, and anorexia. A normalization of liver enzymes and leukocyte 

differential preceded the disappearance of lymphadenopathy and hepatosplenomegaly, 

while positive IgM serology lasted until 36 mo in one p (mean time to disappearance: 

10-26 months). 

POSTERS 

Conclusions 

Primary Cytomegalovirosis is a self-limiting disorder, whose apparent increased 

frequency is probably attributable to a more easy access to specific and sensitive 

laboratory testing. Although a treatment is not indicated in otherwise healthy p, clinicians 

should maintain an elevated suspicion for a primary CMV disease when assessing p with 

FUO, since CMV may cause a prolonged febrile syndrome, and undiagnosed p are at risk 

to be exposed to further, second-level diagnostic workups, due to an apparently 

unexplained febrile disorders, accompanied by a varied clinical picture. 


PP 6.15 

Assessment of need of Patient Hospitalization at an Italian Infectious 

Disease Division 



Introduction 

Notwithstanding the change of HIV natural history, the hospitalization potential of 

Infectious Diseases (ID) wards remains largely inadequate, according to the modification 

of epidemiology and disease spectrum. 

Methods 

A surveillance study of patients (p) needing hospitalization at our ward and their outcome, 

was performed. 

Results 

From January 2000 to May 2002 our inpatient unit could rely on 16 beds only, while since 

June 2003 (after joining with the other ID unit of our 500,000-inhabitant metropolitan area), 

beds rose to 35. The ID Specialist must act as a consultant for every p with a suspected 

ID, to assess need of hospitalization and/or isolation, and eventually search an adequate 

place, should beds are not available at our ward. The rate of p admitted elsewhere 

dropped from 2000 (34.3%), to 2001 (26.9%), 2002 (12.9%), reaching a plateau in 

2003-2005 (12.3%; p

PP 6.16 

Isolation of Corynebacterium spp. organisms in different clinical settings of a large 

teaching Hospital. Focus on intensive care units 

Roberto Manfredi, Anna Nanetti, Samanta Morelli, Roberta Valentini, Leonardo Calza 

Department of Clinical and Experimental Medicine, Division of Infectious Diseases and 

Division of Microbiology, University of Bologna, Italy 

Introduction 

Corynebacterium spp. organisms are commonly isolated bacteria, but their pathogenic 

role is still poorly known. 

Methods 

A bacteriological and clinical survey was conducted on all inpatients of our teaching 

Hospital, in order to identify all Corynebacterium isolates, and to assess them according 

to involved species, clinical materials, and involved hospital settings, with special attention 

paid to intensive care units (ICU). 

Results 

Of 161 Corynebacterium spp. isolates, 17 C. glucuronolyticum strains came from semen 

assessed during FIVET screening procedures, and were not further evaluated. 

Corynebacterium spp. represented the most frequent isolate (78 episodes, with 4-11 

repeated isolations in two patients), followed by C. striatum (33 strains), C. jeikeium (15), 

C. urealyticum (6), C. propinquum (5), C. afermentans (3), C. macgihley, and 

Coryinebacterium group G-1 (two cases each). The most frequent clinical specimens were 

represented by blood cultures (41 cases ), blood/central vascular catheters (14), bronchial 

aspirates/bronchoalveolar lavage (25), ascites or pleural effusion (14), surgical wounds or 

ulcers (13), urine (12), and drainages (11). Interestingly, while all C. jeikeium and 

C. propinquum isolates came from blood and catheters, Corynebacterium spp. prevailed 

(representing over 80% of cases) in blood and lower respiratory tract cultures, and 

C. striatum predominated in wound infections, ulcers, and drainages (over 60%). When 

making a five-year survey of Corynebacterium strains isolated from all ICU since year 

2001, 33 disease episodes were confirmed in 25 patients (16 males and 9 females, aged 

27-90 years). Corynebacterium spp accounted of 15 isolates, followed by C. striatum (9), 

C. jeikeium (5), Corynebacterium group G-1 (3),and C. macginley (1),while among clinical 

specimens bronchial aspirate/BAL prevailed (16 cases),over blood (8), peritoneal 

fluid/abdominal drainage (6),and surgical wounds (3). 

POSTERS 

Conclusions 

Corynebacterium spp. are considered with increasing interest in the last years, but their 

clinical role remains unclear. Based on their unpredictable antimicrobial susceptibility 

profile, further epidemiological, clinical, and therapeutic analyses are therefore 

necessary. 


PP 6.17 

Community-acquired septicemic pneumonia caused by a multiresistant 

Staphylococcus aureus strain, resulting in multiple organ involvement exacerbated 

by extensive immune activation 



Introduction 

Antibiotic-resistant gram-positive cocci are of increasing concern, and immune activation 

promped by microbial products (bacterial superantigens) may play a major role in the 

pathogenesis of disseminated, life-threatening Staphylococcus aureus infection. 

Patient and Methods 

An exceptional case report of community-acquired, severe infection caused by a 

methicillin-resistant S. aureus strain,responsible for pneumonia, septic shock, and 

scattered septic embolism, and accompanied by diffuse polyvisceritis and thrombophlebitis 

as signs of an extensive immune system activation, was seen in a otherwise healthy 

40-year-old man. 

Results 

The striking features of S. aureus polyvisceral disease (pneumonia, septicemia, and 

pulmonary and hepato-splenic septic embolism), were associated with multiple 

immune-mediated focal manifestations (massive pleuric-pericardial effusion, mycocarditis, 

and multiple lower limb thrombophlebitis). In vitro resistance to all beta-lactams, 

fluoroquinolones, macrolides, and aminoglycosides, apparently did not justify the 

clinical-microbiological failure of a glycopeptide-based combination therapy. Only the 

administration of combined linezolid-rifampicin-tetracycline together with intensive care 

support, achieved a slowly progressive ameliorement, while the polyvisceritis (associated 

by an immune-activation syndrome documented by increased CD4+, CD34+, and CD4- 

CD8- T-lymphocyte subsets), caused dysreactive disease at multiple body sites, and 

required a prolonged high-dose steroid therapy. A complete clinical, laboratory, and 

instrumental recovery was reached only three months after admission. 

Conclusions 

This report raises multiple questions about the epidemiology, pathogenesis, clinical 

presentation and manifestations, and management of complicated S. aureus infection, 

with special focus on the immune system activation possibly triggered by microbial 

antigens, and the therapeutic role of steroids and novel antibiotics targeted against 

resistant gram-positive cocci. 


PP 6.18 

Severe, pulmonary atypical mycobacteriosis in a patient suffering from 

decompensated liver cirrhosis, but intolerant to multiple therapeutic attempts. 

Spontaneous resolution in absence of relapses after a three-year follow-up 



Introduction. On the ground of the broad spectrum of anathomic-functional abnormalities, 

dysfunction of enteric tract and portal system, eventual ascites formation, and the 

underlying immunodepression which includes leukopenia-neutropenia, altered cytokine 

network, humoral and osponizing alterations, a decompensated liver cirrhosis is a well 

known risk factors for the development of infectious complications, usually bacterial in 

origin and localized at the abdominal districts. Reliable animal models also demonstrated 

the existence of an increased susceptibility just to atypical mycobacteriosis, to attribute to 

functional macrophage deficits, prompted by an literleukin-12 dysregulation. 

Case report and Comment. An exceptional episodes of severe, extensive pulmonary 

mycobacteriosis due to Mycobacterium avium-complex repeatedly confirmed by culture 

examination, occurred in a patient with decompensated liver cirrhosis, but evolved 

towards sponaneous resolution in the term of around 18 months, despite the 

impossibility to administer an effective antimicrobial chemotherapy, caused by repeated 

patient's intolerance to the numerous attempts. Diagnostic imaging showed sparse, 

numerous micro- and macronodular lung infiltrates (0.2 to 8.0 mm in diameter) involving 

both lungs, while the repeated cultural isolation of M. avium-complex from bronchoalveolar 

lavage fluid allowed organism identificaton and in vitro susceptibility testing. From an 

extensive review of the available international literature, only due episodes compatible 

with a spontaneous resolution of a respiratory infection caused by Mycobacterium terrae 

were found, although an advanced hepatic diseases was absent in both cases, and a 

specific antimicrobial combination chemotherapy had been adminstered for non-negligible 

time periods (Peters EJ, Chest 1991;100:1449-50; Spence TH, South Med J 1996;89:414-6). 

Since liver cirrhosis is frequenty complicated by a bacterial peritoneal localization, but 

atypical mycobacteriosis remains a very infrequent occurrence, our case reports is the first 

described episodes of a serious pulmonary M. avium-complex localization in his context. 

Such an episodes is extraordinarily evolved into a slow, spontanous clearance, as 

documented by extremely reliable examinations, like repeated bronchoscopy with 

bronchoalveolar lavage (BAL), and subsequent microscopical and cultural assays, 

high-resolution computerized tomography (HRCT), and a scintigraphic scan performed 

with radio-marked leukocytes. 

Discussion. When multiple micro- and macronodular pulmonary infiltrates are of concern, 

an atypical mycobacteriosis should be excluded, notwithstanding that such an infection 

remains a rare occurrence in the immunocompetent host, and also during advanced liver 

disorders. The diagnostic tools and the subsequent monitoring are based on invasive 

examinations (bronchoscopy and BAL), high-resolution imaging (HRCT), and 

morpho-functional assays (scintigraphic scans). When considering the available 

therapeutic options, in vitro antimicrobial susceptibility testing have a frequent poor 

reproducibility index, so that the relatioship with the in vivo response to chemotherapy is 

sometimes unpredictable. When escluding extremely infrequent episodes (like that 

reported by us), a 3-4-drug combination therapy is generally recommended: 

clarythromycin or azithromycin, ethambutol, amikacin, rifabutine, fluoroquinolones and 

clofazimine are the most frequently used compounds in this setting. 

POSTERS 


PP 6.19 

Multiple sclerosis managed without immunosuppressive therapy. 

Detection of pulmonary zigomycosis as an indolent fungal complication 



Introduction 

Mucormycosis (M) is a infrequent filamentous fungal infection borne by a very elevated 

fatality rate despite prompt diagnosis and adequate therapy, especially in its frequent 

rhinocerebral presentation, and/or when decompensated diabetes mellitus, neutropenia, 

or immunosuppression are of concern. 

Case Report 

A 53-year-old female patient (p) with a multiple sclerosis previously treated with steroidsazathioprine 

(but controlled since three months without any treatment), was hospitalized 

owing to cough and hemophtoe, in absence of dyspnea, other respiratory symptoms, and 

fever. Laboratory testing did not disclose significant abnormalities (total leukocyte count 

and differential, ESR, and serum glucose were within noraml limits), and tumoral markers 

tested negative, but the detection of multiple lung infiltrates at chest X-ray and HRCT 

(predominant at right lobes, with an appreciable air bronchogram), prompted a 

bronchoscopy with biopsy and bronchoalveolar lavage involving the medial right lobar 

bronchus area. After an uncertain microscopy (with Aspergillus hyphae still suspected), 

and negative serum Aspergillus antigen search, cultures led to the isolation of Mucor spp., 

with tested in vitro susceptible to amphotericin B and posaconazole, while it was resistant 

to itraconazole and voriconazole. Liposomal amphotericin B (at 3 mg/Kg/day) was 

delivered for six weeks predominantly on Day-Hospital basis with favorable tolerability: no 

hematological, blood chemistry and urinalysis alterations occurred. One month later, our 

p completely recovered, and a repeated HRCT and bronchoscopy confirmed a complete 

clinical, radiological, and mycological cure. 

Discussion 

M is a rare occurrence, especially when neutropenia and ketoacidosis are absent. 

However, anecdotal reports occurred after trauma, and during COPD. Although the usual 

portal of entry of M is respiratory, however the rhinocerebral M remains the most frequent 

and life-threatening presentation. Clinicians should consider M even when obvious risk 

factors and an apparently slow progression are found. The diagnostic procedures includes 

microscopic differentiation from Aspergilli, although mixed infections are not so rare. In 

pulmonary forms, percutaneous biopsy becomes sometimes needed. Liposomal 

amphotericin B remains the treatment of choice, but surgery is sometimes necessary, in 

order to debride extensive necrotic areas due to angioinvasion; some doubt remains 

about the role of hperbaric O2 therapy. In our p, a slowly progressive pulmonary M was 

identified and cured in a reasonably short time, even in absence of underlying, active risk 

factors, and a rapidly overwhelming clinical progression. 


PP 6.20 

Severe mediastinal tuberculosis complicated by main bronchial and thoracic aortic 

compression and long-term esophageal fistulization, in a patient with negative 

history and pulmonary signs and symptoms of tuberculosis 



Introduction 

Tuberculosis is increasing significantly in its frequency, especially among immigrants, 

where non-pulmonary localization are of diagnostic-therapeutic concern. 

Case Report 

A 30-year-old male recently immigrated from Bangladesh, was hospitalized in an Internal 

Medicine Department with a mute tuberculosis history, due to a worsening dysphagia and 

severe weight loss: a malignancy was initially suspected. Laboratory testing showed an 

isolated ESR increase, in absence of positive tumoral markers. A routine chest X-ray 

proved normal, but an esophagoscopy showed an extrinsic visceral compression. Later, 

an ultrasonographic-endoscopic study and repeated thorax CTs disclosed a mediastinal 

mass with a colliquative centre of around three cm diameter which ulcerated the 

esophageal lumen, compressed the left bronchus, leaning on the thorax aortic tract. 

Multiple sparse lymphnodes undergoing colliquation completed the mediastinal 

involvement, while a contrast-enhanced esophagogram showed an extensive fistulization 

between the esophagus and the necrotic, colliquated mediastinal abscess. After negative 

sputum examinations, the culture diagnosis of tuberculosis was obtained by a 

transbronchial bronchoscopy, while the tuberculosis skin test (Mantoux) proved intensely 

positive. A well-tolerated foud-drug classical anti-tubercular therapy was performed for 

three months,followed by a three-drug combination still ongoing since three more months, 

together with proton pump inhibitors to contain dysphagia. At the last chest CT scan and 

esophagogram, the mediastinal lesion and the reactive lymph nodes were significantly 

reduced in size, calcific lesions substituted colliquative areas, while a narrow esophageal 

fistulization was still present. 

POSTERS 

Discussion 

Our rare case of tubercular mediastinal abscess with extensive esophageal fistulization, 

treated favourably with conservative medical therapy, reminds that tubercuosis may 

mimick multiple pathologic conditions, with diagnosis and treatment often reached 

despite the absence of both tuberculosis-compatible history and pulmonary lesions. 

The differential diagnosis of tubercular lesions involves a broad spectrum of diseases, and 

tuberculosis should be never neglected, even when an evident history and lung 

involvement are absent. The recent,explosive rise of tuberculosis among immigrants in 

Italy, is a serious epidemiologic and social health concern when summarized with the 

increased life expectancy and the greater risk of immunosuppressive conditions in the 

general population. A strict monitoring of tuberculosis is strongly needed, in order to plan 

adequate diagnostic-preventive measures, and to allocate the needed health care 

resources. 


PP 6.21 

A serious staphylococcal knee and soft tissue infection responsive to linezolid only, 

after failure of all other therapeutic attempts. Discrepancy between favorable in 

vitro bacteriological testing and a worsening clinical course 



Introduction 

To offer therapeutic alternatives for the emerging, multiresistant, serious gram-positive 

infections, novel molecules (quinupristin/dalfopristin, linezolid, daptomycin, tigecyclyne), 

have been recently introduced, and are made available when multiresistant gram-positive 

cocci are documented, like absence of susceptility to all available drugs, including 

glycopeptides. However, linezolid encompasses unique tissue penetration and diffusion 

features (regarding soft tissues, lungs, joints, and central nervous system), which make 

this last drug extremely promising in all circumstances where the penetration rate into 

infectious foci becomes critical. 

Clinical experience 

A very intriguing case report of a severe, staphylococcal knee arthtiris associated to an 

extensive local cellulitis/necrotizing fasciitis and hematogenous dissemination occurring 

after a surgical curettage, was characterized by a complete lack of response to a 

prolonged vancomycin/teicoplanin plus rifampicin therapy, based on the apparently 

favorable in vitro sensitivity assays of methicllin-resistant Staphylococci, but rapidly 

responded to i.v. (followed by oral) linezolid administration. The complete lack of clinical 

activity of a two-week glycopeptide-rifampicin administration cannot be explained by the 

in vitro measured MIC90 values of isolated pathogens,which showed complete sensitivity 

of Staphylococcus aureus against vancomycina/teicoplanin and rifampicin, and 

susceptibility of a concurrent hematogenous S. epidermidis strain to glycopeptidesrifampicin. 

Since an abscess formation and an underlying osteomyelitis were carefully 

excluded by adequate instrumental examinations, from a theoretical point of view the 

active glycopeptide-rifampicin molecules should have been provided appropriate cure.On 

the other hand, from a strictly clinical issue, only a two-week administration of i.v. 

linezolid followed by one more week of oral linezolid, allowed to obtain a complete 

clinical-bacteriological cure, and a complete function recovery, without any sequelae after 

a two-year follow-up. 

Conclusions 

When the management of severe, multiresistant gram-positive infections is of concern, the 

in vitro activity of single drugs and therapeutic classes should be carefully evaluated in 

relation with the expected penetration and diffusion rates of these drugs into the relevant 

organs and tissues involved by the ongoing infectious localizations. Otherwise, 

apparently unexplained failures may occur also when in vitro studies point out a 

complete activity of the tested compounds. 


PP 6.22 

Expression of fused B subunit of heat-labile enterotoxin and a linear epitope of 

colonization factor antigen I of Escherichia coli 

Nader Shahrokhi, Saeid Bouzari, Amir Dashti and Anis Jafari 

Molecular Biology Unit, Pasteur Institute of Iran, Tehran, Iran 

Enterotoxigenic Escherichia coli (ETEC) is one of the most common causes of acute 

diarrhea in children in developing countries and in travelers who visit ETEC-endemic 

areas. ETEC strains are identified by their ability to produce either heat-labile (LT) or 

heat-stable (ST) enterotoxin or both and surface adhesins known as colonization factors 

(CFs). Adherence of bacteria to the epithelial surface of the small intestine and delivery of 

toxin are the two most important events in ETEC pathogenesis. In several human settings, 

protective immunity has been associated with immune response to colonization factors 

and to the heat-labile toxin. Although there are many CFs, CFA/I is one of the most 

frequently found CF in epidemiological studies and the linear epitope at the N-terminal 

part of its structural subunit (B subunit) shares sequence similarity with the structural 

subunits of a number of other CFs. Furthermore, the B subunit of LT which hinds to GM1 

ganglioside is a strong immunogen and induces both systemic and mucosal responses 

following administration and also has strong adjuvant activity as a carrier protein for 

co-administered unrelated antigens. Therefore, in the present study the coding region of 

LTB and the N-terminal linear epitope of CFA/I B subunit were amplified with an 

overlapping polyglycine tag at 3' and 5'-end of each fragment respectively to function as 

a short linker between LTB and the linear epitope in the expressed recombinant hybrid 

protein. The two fragments were assembled by a further PCR and the assembled 

chimeric gene was sequenced for confirmation of accuracy. The assembled gene was 

cloned and expressed in E. coli using pBAD/gIII A expression system. The expressed 

recombinant fused protein carried C-terminal myc epitope facilitating detection of the 

expressed protein by Western Blot analysis using anti-myc. Antigenicity of the 

recombinant protein was assessed using anti-CTB antibody. Furthermore, 

receptor-binding ability of the recombinant fused protein was ascertained in GM1-ELISA 

using both anti-myc and anti-CTB antibodies. We are currently evaluating 

immunogenicity of the expressed protein. 

POSTERS 


PP 6.23 

Comparison between Secretory Leukocytic Protease Inhibitor and Reactive 

Nitrogen Intermediates Levels in Cervicovaginal Secretions from symptomatic and 

Asymptomatic Trichomoniasis Egyptian Patients 

Hamdan I. Al-Mohammed and Eman M. Hussein 

Departments of Parasitology and Microbiology, Faculties of Medicine, King Faisal 

University, P O Box 550017, Al-Ahsa, 31982, Saudi Arabia¹ and Suez Canal University, 

Ismailia, Egypt. 

Objectives 

Although trichomoniasis is one of the most widespread sexually transmitted diseases, 

limited information was known about the host and parasite factors which causing 

symptomatic versus asymptomatic infections. Both of Secretory leukocytic protease 

inhibitor (SLPI) and Reactive Nitrogen Intermediates (RNI) are major effectors in the 

innate immune response against infection. SLPI is a potent inhibitor of human leukocyte 

elastase and is important in preventing HIV infection. RNI is free radicals generated during 

inflammatory process. So, this study aimed to compare the level of SLPI and RNI in 

relation to the vaginal complains among trichomoniasis Egyptian patients. 

Methods 

Two groups of patients included in this study; group I included 30 symptomatic patients 

distributed in three equal subgroups mild, moderate and severe according to degree of 

symptoms (10 patients in each) and group II included 10 asymptomatic. Beside, control 

group III included 10 healthy females. Level of both SLPI and RNI were assed by ELISA. 

Values were represented means ± S.E.M. ANOVA and Mann-Whitney U-test were applied 

in statistical analysis. 

Results 

Levels of SLPI were lower in symptomatic patients in compared to asymptomatic and this 

difference was statistically significant. In addition, levels of SLPI were significantly lower 

in severe symptomatic patients in compared to mild and moderate subgroups 

respectively. This difference was statistically significant. In controversy, mean 

concentration levels of RNI in symptomatic patients were significantly higher than 

asymptomatic group. Also, mean levels of RNI were significantly higher in severe 

symptomatic patients in compared to mild and moderate subgroups respectively. 

This difference was statistically significant. Both of SLPI and RNI levels were returned to 

the normal levels in 93.4% and 80% of symptomatic patients respectively after one week 

from beginning of the course of treatment. 

Conclusions 

SLPI and RNI had an inverse relationship in symptomatic patients. In addition, innate 

immune response of trichomoniasis patients was different in relation to the severity of 

symptoms. It may be due to different macrophages populations and its function 

capabilities or to difference in T. vaginalis isolates which induce different clinical degree of 

symptoms with variability of the innate immunity response. 


PP 6.24 

Controversies in the antimycotic management of Candida albicans 

panophthalmitis: an exemplary case report and discussion of guidelines of 

antifungal chemotherapy 



Introduction 

Candida endophthalmitis is a severe function-threatening infection, more frequent in 

immunocompromised p, or among p with selected supporting conditions. 

Case report 

A 55-year-old man with an insulin-dependent diabetes was hospitalized due to a sudden 

vision loss at right. After a diagnosis of C. albicans panuveitis, a treatment with i.v. 

fluconazole (400 mg/day) was started. Since a worsening of ophthalmologicfluorangiographic 

picture paralleled the appearance of amblyopia, 10 days later liposomal 

amphotericin B (lAB) (at 3 mg/Kg/day) replaced fluconazole, and after 14 days a 

remarkable reduction of exudates was achieved. After 17 days lAB was stopped due to 

am overwhelming kidney function deterioration (serum creatinine 2.11 mg/dL, and 

azotemia 1.32 g/dL, versus normal values upon admission), and i.v. caspofungin was 

administered at standard dosage. After 48 days of caspofungin therapy (at 50 mg/day) 

delivered on Day-Hospital basis, active foci were still present at fluorangiography, and 

visual acuity recovered up to 2/10, while renal impairment spontaneously disappeared. 

Finally, i.v. voriconazole (at 400 mg/day) was started and continued for 23 days. After this 

last course, our p obtained a complete resolution of exudates at ophthalmoscopic-fluorangiographic 

study, and visual acuity rose to 6/10. Oral voriconazole (400 mg/day) was 

recommended upon discharge. 

Discussion 

The rationale of antifungal therapy of Candida endophthalmitis is limited by the 

unfavorable kinetics of several compounds, and the absence of randomized controlled 

trials in this setting, so that most informations come from small series and anecdotal 

reports. While fluconazole may be limited by its reduced activity on some non-albicans 

Candida, lAB is the standard of care (administered by intraocular and/or systemic route), 

but isolated failures were reported. The endovitreal penetration of caspofungin is 

discussed (although favorably treated p are described), while voriconazole (either as 

systemic or local injection agent) led to preliminary, satisfactory results. Our p with a 

severe Candida endophthalmitis received all the four available antimycotic agents 

effective against C. albicans (i.e. fluconazole, liposomal amphotericin B, caspofungin, and 

voriconazole), but experienced disease progression during fluconazole and probably 

long-term caspofungin administration, while the initially favorable lAB response was 

hampered by reversible kidney function anomalies, and voriconazole proved safe and 

effective in leading to a complete cure and a favorable recovery of visual acuity. 

Prospective, controlled studies are strongly needed, to trace some therapeutic guidelines 

of Candida panophthalmitis. 

POSTERS 


PP 6.25 

Real- Time PCR and Flow Cytometry for Detection of Cyclospora Oocysts from 

Fecal Samples of Gastrointestinal Symptomatic and Asymptomatic Patients 

Eman M. Hussein¹, Amal A. El-Moamly¹, Hamdy A. Dawoud¹ and Hanaa Fahmy ² 

Departments of Parasitology1 and Clinical Pathology², Faculty of Medicine, Suez Canal 

University, smailia, Egypt. 

Objectives 

Cyclospora cayetanensis has emerged as an important human pathogen that causes 

enteric disease in both immunocompromized and immunocompotent hosts. Also, 

asymptomatic patients excrete oocysts in their stool were identified. Until Now, the 

difference in parasitic load among cyclosporaisis patients was not detected. In this study, 

the magnitude of oocysts excretion in relation to the pathological severity was assessed 

among cyclosporiasis patients with using Flow Cytometry and quantitative Real- time 

PCR. 

Methods 

Oocysts from stool samples of 25 symptomatic and 10 asymptomatic gastrointestinal 

cyclosporiasis patients were identified by both modified Acid Fast Trichrome and modified 

Ziehl-Neelsen staining methods and were confirmed by its auto-fluorescent 

characterizations. In addition, 10 persons with negative stool samples were selected as 

control group. The intensity of infection was calculated by number of oocysts/200 

microscopic filed with immersion 400. Flow cytometry and quantitative Real- time PCR 

were used to assess the relation between the degree of infection and magnitude of 

oocysts excretions. Statistical analysis was applied using X2. 

Results 

The degrees of infection among symptomatic patients were identified by staining methods 

as mild in 16%, moderate in 24% and severe in 60%. All of asymptomatic patients were 

in mild infection degree. Flow cytometry was conducted to all samples and Cyclospora 

oocysts were identified in 100% and 80% of symptomatic and asymptomatic patients 

respectively. This difference were statistically significant (P

FP 0.1 

Thiovir exhibits broad-spectrum antiviral activity against human and avian 

influenza viruses, human immunodeficiency viruses, and herpes simplex viruses 

Shani Waninger, Silvestre Ramos and Joan Robbins 

Adventrx Pharmaceuticals, San Diego, CA 92121, USA 

Objective 

Thiovir (thiophosphonoformic acid) is a prodrug of the broad-spectrum antiviral-drug 

foscarnet (phosphonoformic acid). Foscarnet currently has limited therapeutic usage, in 

part because of its intravenous route of delivery. In contrast, Thiovir has increased 

bioavailability that enables oral delivery. Based on the broad-spectrum activity of 

oscarnet, we examined the antiviral activity of Thiovir against multiple virus types, 

including human and avian influenza, human immunodeficiency virus (HIV) and herpes 

simplex viruses (HSV). 

Methods 

Antiviral activity of Thiovir and foscarnet was tested using in vitro viral infection assays. 

Activity against influenza virus infection of MDCK cells was determined by either a plaque 

assay or ELISA. Anti-HIV activity was determined by the PhenoSense assay. Activity 

against HSV infection of Vero cells was determined by a plaque assay. In all assays, cells 

were pre-incubated with drugs for approximately 30 minutes before virus addition. 

Results: We observed dose-dependent antiviral activity of Thiovir against multiple 

subtypes of human and avian influenza A and human influenza B virus. Similarly, Thiovir 

inhibited two types of herpes simplex virus, HSV-1 and HSV-2. Thiovir was also active 

against multiple HIV-1 clades, HIV-2, and HIV strains resistant to current antiretroviral 

therapies. For all virus types, the level (IC50) of antiviral activity for Thiovir was similar to 

foscarnet. 

Conclusions 

Thiovir demonstrated effective and broad-spectrum antiviral activity against HIV, HSV, and 

human and avian influenza viruses in vitro. The broad activity, combined with the 

increased oral bioavailability, suggests Thiovir may have an increased therapeutic 

advantage compared to foscarnet. Furthermore, the antiviral activity of Thiovir against 

human and avian influenza suggests Thiovir may have applications in the event of global 

bird flu pandemic. 

POSTERS 


FP 0.2 

Preclinical Development of a Novel Long-acting HIV-1 Fusion Inhibitor 

He Jiang 1,3 , Li Wang 2 , Min Zhang 2 , Cheng Yao 1 ,Wenjie Min 1 , Mingxian Huang 1 , 

Tianxi Shan 1 , and Dong Xie 1 

1 

Frontier Biotechnologies Co., 3 rd Floor, Building I, 70 Keyuan 4 th Street, Bio-Garden, High- 

Tech Zone, Chongqing, China 400041 

2 

Chengdu GLP Center, 20 Gao Peng Blvd., High-Tech Zone, Chengdu, China 

3 

Dept. of Pharmaceutical Engineering, Chongqing Institute of Technologies, 4 Xingsheng 

Rd, Yang Jiaping District, Chongqing, China 400050 

Objectives 

Utilize albumin-conjugation technology to design and develop potent and long-acting, 

peptide-based HIV-1 fusion inhibitors; determine preclinical efficacy, pharmacokinetic, and 

safety profiles for the lead compound, albuvirtide. 

Methods 

Peptide sequences from the C-heptad repeat of HIV-1 gp41 was modified such that they 

exhibited increased solubility and anti-HIV activity, and were able to rapidly form covalent 

conjugate with albumin. Albumin binding was characterized in PBS buffer and in plasma 

using liquid chromatography-mass spectrometry; anti-HIV activity was evaluated in vitro 

against laboratory and clinical isolates of HIV-1 in a variety of assay systems (PBMCs, 

MDM, MAGI, CEM-SS, etc.); in vivo efficacy was assessed in a SCID/hu Thy/Liv mice 

model; pharmacokinetic, immunogenicity, acute- and chronic-toxicology studies were 

performed in rat and monkey. 

Results 

Binding study showed that albuvirtide rapidly and irreversibly formed 1:1 (molar ratio) 

conjugate with serum albumin in blood. Albuvirtide-albumin conjugate exhibited potent 

and broad-spectrum anti-HIV activity independent of viral tropism, with IC 50 values ranging 

from 0.5 to 4.8 nM. It also strongly inhibited infections by 7 enfuvirtide-resistant HIV-1 

mutants. Toxicology studies of albuvirtide demonstrated excellent safety profiles. Neither 

immunotoxicity nor antibody was observed after repeated dosing in 3 months. 

Pharmacokinetic studies exhibited a remarkably extended half-life in vivo. In rhesus 

monkey, the terminal half-life and AUC 0-360hr of albuvirtide was 40- and 17.6-fold higher 

than that of the unmodified peptide, respectively. 

Conclusions 

Conjugation with albumin did not compromise the antiviral activity of albuvirtide, while 

ubstantially extended its half-life in vivo. On the basis of the broad and potent antiviral 

activity, favorable safety, and advantageous pharmacokinetic profiles, albuvirtide is a 

promising new drug candidate for treating HIV/AIDS. 


FP 0.3 

Viral shedding of avian influenza virus in recovered patients from Thailand. 

Sontana Siritantikorn, Wannee Kantakamalakul, Kulkanya Chokpaibulkit, Suksan 

Assanasen, Nawin Horthongkham, Duangnapha Arwon, Kawinyanee Loengaram, 

Ruengpung Sutthent 

Department of Microbiology, Pediatric, Medicine, Faculty of Medicine Siriraj Hospital, 

Mahidol University, Thailand. 

Background 

In 2005, there were 5 human infected cases of avian influenza (H5N1) reported from 

Thailand, 3 cases were admitted at Siriraj Hospital and alive. In order to improve 

diagnostic and infection control of avian influenza virus in human, the virus from 

nasopharyngeal secretion and feces of these survivals were studied. 

Methods 

The nasopharyngeal wash (NPW) and feces were collected alternative day. Avian 

influenza virus was detected by reverse transcriptase PCR (RT-PCR) and culture in 

MDCK cell line. 

Results 

The duration of virus excretion in NPW and stool detected by RT-PCR was 17.3 (16-19) 

and 8 (7-9) days after the day of onset, respectively. The phylogenetic analysis of 

hemagglutinin gene from these isolates were clustered with the first avian influenza virus 

human isolate from Thailand (A/Thailand/1(KAN-1/04HA). There was no genetic 

compartmentalization of avian influenza virus in both clinical samples. 

Conclusions 

The presence of avian influenza virus in human feces will have effect on infection control. 

FREE ORAL PRESENTATIONS 


FP 0.4 

Primary Resistance of a Novel Hepatitis B Virus Variant to Adefovir 

Oliver Schildgen PhD 1* , Hueseyin Sirma MD 5* , Anneke Funk PhD 5 , Cynthia Olotu 5 , Ulrike 

C. Wend 2 , Heinz Hartmann MD 3 , Martin Helm 4 , Jürgen K. Rockstroh MD 1 , Wulf R. 

Willems MD 2 , Hans Will PhD 5§ , Wolfram H. Gerlich PhD 2§ 

1. Institute of Medical Microbiology and Immunology and Department of Medicine I 

University of Bonn, Germany 

2. Institute of Medical Virology, University of Giessen, Germany 

3. Practice for Gastroenterology and Hepatology, Herne, Germany 

4. Practice Abelein/Helm, Nuremberg, Germany 

5. Heinrich-Pette-Institut, Hamburg, Germany 

* The first two authors contributed equally to this work. 

§ The last two authors contributed equally to this work. 

Introduction 

We observed three HBV-infected patients that displayed no decrease of the viral load 

under therapy with adefovir; a therapy switch to tenofovir resulted in a significant drop of 

the viral load. 

Methods 

HBV DNA was isolated and the DNA polymerase gene was amplified by PCR for 

sequencing. Sequencing was carried out using the BigDye terminator reaction. 

Genotyping and identification of mutations were performed with the INNO-LiPA assay and 

by sequencing of PCR products. The relevance of the mutation rtI233V for Adefovir 

resistance was tested by site-directed mutagenesis of standard HBV genotype D wt and 

transfection of a hepatoma cell line. 

Results 

Adefovir was ineffective in all three patients. Sequencing analysis of all HBV strains 

analysed from the patients revealed no amino acid exchange at the Adefovir-resistance 

positions rt236 or rt181. All patients were infected with HBV genotype D, accompanied 

HBsAg subtype ayw4, and displayed a unique mutation rtI233V. The resistance to 

adefovir mediated by this mutation was confirmed by the in vitro resistance testing. 

Replication of the transfected variant was not inhibited by Adefovir. 

Conclusion 

Based on our present observations and our recent data (Schildgen et al.; AIDS 

18(17):2325-7) we conclude, that polymorphisms like rtI233V in the polymerase/reversetranscriptase 

domain aa 215 to aa 236 mediate adefovir resistance. In contrast to the 

known resistance mutations at rt181 or rt236, the variant rtI233V exists before therapy. 

Based on our in vivo observations, we strongly recommend to consider a therapy change 

to tenofovir whenever this variant is observed. 


FP 0.5 

The epidemic history of hepatitis C among drug users in Flanders, Belgium 

Matheï Catharina (1) Van Dooren Sonia (2) Lemey Philippe (2) Van Damme Pierre (3) 

Buntinx Frank (1) Vandamme Anne-Mieke (2) 

(1) ACHG, KUleuven, Leuven, Belgium (2) Klinische en evolutionaire virologie, KUleuven, 

Leuven, Belgium (3) Epidemiologie en Sociale Geneeskunde, UA, Antwerp, Belgium 

We employed recently developed molecular methods to explore the epidemic behaviour 

of hepatitis C subtype 1a and subtype 3a among injecting drug users in Flanders, 

Belgium, using new gene sequence data sampled among two geographic distinct 

populations of injecting drug users. First the extent of hepatitis C transmission across 

regions/countries was studied through calculation of association indices. It was shown that 

viral exchange has occurred between both populations in Flanders as well as across 

international borders. Furthermore evidence was found suggestive for subtypes 1a and 3a 

predominantly circulating in subpopulations of Flemish IDUs exhibiting different degrees 

of travelling/migration behaviour. Second, through coalescent based analysis the viral 

epidemic history of the hepatitis C subtype 1a and 3a epidemics was inferred. Evidence 

was found for different dynamic forces driving both epidemics. Also, the results suggested 

that the hepatitis C subtype 3a epidemic has reached a steady state, while the hepatitis C 

1a epidemic has not, which therefore might become the predominant subtype among 

injecting drug users. 



FP 1.1 

In Vivo Emergence of RANTES-Resistant Simian Immunodeficiency Virus in Pig- 

Tailed Macaques Coinfected with Human Herpesvirus 6A 

Angélique Biancotto 1 , Jean-Charles Grivel 1 , Andrea Lisco 1 , Christophe Vanpouille 1 , 

Phillip D. Markham 2 , Robert C. Gallo 3 , Leonid B. Margolis 1 and Paolo Lusso 4 

1 

Laboratory of Molecular and Cellular Biophysics, National Institute of Child Health and 

Human Development, Bethesda Maryland 20892 USA 2Advanced Bioscience 

Laboratories, Kensington, Maryland 20895 USA 3Institute of Human Virology University of 

Maryland Biotechnology Institute, Baltimore, MD 21202 USA 4Unit of Human Virology, 

DIBIT San Raffaele Scientific institute, Milano, Italy and Department of Medical Sciences, 

University of Cagliari Medical School, Cagliari, Italy 

Human immunodeficiency virus (HIV) disease is associated with de novo or reactivated 

infection by a variety of other microbes that may modulate the pace of disease 

progression. Human herpesvirus 6 (HHV-6) variant A, a CD4+ T-lymphotropic virus that 

has been suggested to accelerate the progression of HIV-1 infection toward AIDS, was 

shown in an ex vivo model to suppress CCR5-dependent HIV-1 through an enhanced 

secretion of the CC-chemokine RANTES, conferring a selective growth advantage to 

CXCR4-using HIV-1. Here, we studied the biological properties of SIV isolates obtained 

from pig-tailed macaques (M. nemestrina) coinfected in vivo with HHV-6A, which 

underwent an accelerated disease progression compared to singly SIV-infected 

macaques. Using both human and simian lymphoid tissues, we found that in vivo 

coinfection with HHV-6A induced SIV to become resistant to RANTES-mediated inhibition 

or even to grow more efficiently in the presence of RANTES, despite retaining a 

dependence on CCR5 as a coreceptor. Moreover, SIV isolates obtained from 

HHV-6A-coinfected animals showed a reduced replicative capacity in the absence of 

exogenous RANTES, as well as an altered cytokine-induction capacity. In agreement with 

our previous results, RANTES resistance/inducibility closely correlated with resistance to 

or inducibility by HHV-6A coinfection ex vivo. These results demonstrate that coinfection 

with an unrelated virus can affect the in vivo evolution of SIV providing a basis for 

understanding the accelerated SIV disease progression observed in HHV-6A-coinfected 

monkeys. The acquisition of RANTES resistance, which has also been documented in 

human subjects during the progression of HIV-1 disease, may represent a critical 

virulence factor that permits primate immunodeficiency viruses to thrive in a high-RANTES 

environment bypassing a major mechanism of in vivo virus control. 


FP 1.2 

Natural Suppressors, HIV-1 Viral Suppression in the Absence of Therapy 

Sajadi MM, Heredia A, Le N, Chan-Tack K, Constantine NT, DeVico A, Redfield R. 

Institute of Human VirologyUniversity of MarylandBaltimore, Maryland 

Objectives:HIV Natural Suppressors (NS) are individuals with HIV-1 that are able to 

completely suppress HIV viral replication in the absence of antiretroviral therapy. By 

contrast, Long-Term Nonprogressors (LTNP), represent individuals who are HIV-1 

infected but who maintain immunologic function over many years (no where in the de 

finition of LTNPs is viral load considered, and in most series the HIV-1 viral loads range 

from 102 to 104 copies/ml). We present here the largest and most detailed study of such 

patients that has been undertaken, characterizing the host and viral factors that make 

these patients unique. 

Methods:Inclusion/Exclusion Criteria:1) HIV-1 positive by Western Blot2) Viral loads 400, allowed per every 10 times viral load 

checked).3) No more than 2 weeks of ART use, unless during pregnancy 

Studies: included PCR for HLA Typing, PCR for the CCR5 delta-32 mutation, High Input 

PCR for Proviral DNA copy number, HIV-1 virus isolation, Neutralization antibody tests, 

chemokine activity, and replication kinetics (PBMCs infected with 3B and JRCSF strains 

at moi of .0001 and .001). 

Results:40 patients were identified as NS, and 22 have been enrolled. A prevalence rate 

of 1.5% NS in our clinic population was calculated. Demographics are shown in the table 

below. 

Age 51 (range 38-59) 

Sex Male-55% Female-45% 

Race 

African-American-100% 

Median years with HIV 8.5 (range .5-18) 

Median years viral suppression 5 (range .5-9) 

Median of latest CD4 count (cells/ul) 970 (range 523-1342) 

Average number of viral loads

Conclusion:Patients with HIV-1 infection who are able to naturally suppress HIV infection 

in tbe absence of therapy represent one particular extreme of HIV infected patients and 

are a distinct entity that may yield insight into the virus-host interaction and pathogenesis 

of HIV-1 infection. Although these patients share some features with LTNPs (HLAB57 

status, CCR5 heterozygosity), the striking finding in this study is the degree of resistance 

to HIV-infection of PBMCs. Further studies are ongoing to determine the exact mechanism 

of this resistance. 


FP 1.3 

An in vitro System for HIV-1 Selective Transmission using Human Genital 

Epithelial cells 

Z.W. Wu 1 , G.F. Fu 1 , Y.Y. Hou 1 , and Z.W. Chen 2 

1 

Center for Public Health Research, Nanjing University, Nanjing, China; 

2 

Aaron Diamond AIDS Research Center, New York, USA 

Objectives 

An in vitro culture system, using human genital epithelial cell lines, was established for 

investigating HIV-1 sexual transmission. The system was used to study the efficiency of 

CCR5 and CXCR4 virus transfer from the epithelial cells to CD4+ cells and the 

mechanisms of selective transmission during sexual transmission of HIV-1. 

Methods 

Ect1, End1 and VK2 are HPV E6/E7 gene-transformed human ectocervical, endocervical 

and vaginal epithelial cell lines, respectively. These cells formed monolayers in culture, 

with morphology similar to their corresponding tissues. The culture monolayers were 

pulsed with CCR5 or CXCR4 using HIV-1 and washed off unbound viruses. H9 cells or 

IL-2-stimulated human PBMCs were co-cultured with the monolayers for 18 hours, 

recovered and then re-cultured for a period of 6-9 days. Virus production was monitored 

sequentially and the relative transmission efficiency of CCR5 and CXCR4 viruses was 

investigated. 

Results 

All three epithelial cell lines were refractory to HIV-1 infection due to the lack of CD4 

expression. However, virus can efficiently adsorbed to the epithelial monolayers via heparin 

sulfate moiety of proteoglycans and remained infectious for up to 9 days in culture. The 

adsorption and releasing of CCR5 and CXCR4 viruses were not significantly different. 

Upon co-culture with IL2-stimulated human PBMCs, CCR5 virus was efficiently 

transmitted and replicated in the PBMCs. To the contrary, CXCR4 virus was poorly 

transmitted and replicated though evidence showed that the virus was not defective since 

it replicated well when a T cell line (H9) was used. Preliminary studies showed that the 

differential replication of CCR5 and CXCR4 viruses in PBMCs did not account for the 

differences of CCR5 and CXC4 viruses in co-cultured PBMCs, suggesting that CXCR4 

virus was blocked during the transfer from the epithelial cells to the PBMCs. 

Conclusions 

1. The human genital epithelial cell-based in vitro culture system is a suitable tool for 

investigating the mechanisms of HIV-1 sexual transmission; 

2. CCR5 and CXCR4 viruses were differentially transmitted from the epithelial cells to 

IL-2-stimulated human PBMCs with CXCR4 virus largely blocked during the co-culture; 

3. The epithelial-PBMCs interface may play important roles in selecting virus transmission 

and this co-culture system may serve to delineate the molecular mechanisms of viral 

sexual transmission. 



FP 1.4 

V1V2 loop length variation during HIV-1 infection 

Yi Liu 2 , Wenjie Deng 2 , Geoffrey Gottlieb 1,2, , Rafael Zioni 2 , Marcel E. Curlin 1 Tuofu Zhu 2,3, 

James I. Mullins 1,2,3 

University of washington Departments of Medicine 1 , Microbiology 2 and Laboratory 

Medicine 3 ; University of Washington School of Medicine, Seattle, Washington. 

Objective We sought to determine the relationship between envelope hypervariable region 

loop-length and disease progression and transmission to a new host during HIV infection. 

Methods Sequences were derived from published and unpublished envelope sub-regions 

from treatment-naive adult subjects harboring HIV-1 subtype B. We collected a total of 

4736 gene sequences from individual subregions, derived from 455 clinical samples 

(usually PBMC or plasma) from 144 subjects. Sequences were aligned using ClustalW, 

translated into amino acid sequences and manually edited to identify the V1V2, C2, V3, 

C3, V4, C4 and V5 regions. Subregion lengths were calculated, and potential N-linked 

glycosylation sites were counted using N-glycosite. Data were analyzed treating each 

sequence individually, and repeated as a weighted average of all sequences contributed 

by a given individual. In cross-sectional analyses, loop length variation was examined as 

a function of time since infection, CD4 count, viral load, and calendar year. In longitudinal 

analyses, loop lengths were examined as a function of time between sampling. We also 

examined loop-length variation during transmission to a new host. Results V1V2 displayed 

the most length variation of any region examined. In cross-sectional analyses, a 

significant positive correlation was observed between V1V2 length increase and time 

since infection (p < 0.05), and calendar year (p < 0.05). A weak inverse relationship was 

noted between V1V2 length and CD4 count. However, no relationship was seen with viral 

load, or whether sequences were obtained from plasma or PBMC. In longitudinal 

analyses, V1V2 loop length was generally seen to increase over time in subjects with 

chronic HIV infection (not AIDS). However, in subjects with advanced disease (CD4 count 

< 200), V1V2 loop length decreased over time. Transmission between hosts was usually 

but not always associated with an initial decline in V1V2 loop length. V5 was the next most 

variable region, but did not change in any consistent way in relationship to the parameters 

examined. Changes in the number of glycosylation sites generally paralleled length 

variation. Discussion Structural studies indicate that the V1V2 region shields V3 prior to 

CD4 binding, and is intimately involved in conformational changes allowing coreceptor 

binding site exposure, and coreceptor binding. Viruses lacking V1 and V2 replicate 

efficiently in vitro, but are highly sensitive to neutralizing antibodies. Therefore, the 

principal role of the V1V2 region may be to permit evasion from humoral immune 

responses in the host. Our observations are consistent with the hypothesis that HIV 

adapts to humoral selective pressure within the immunocompetent host by increasing the 

size of V1V2, either by lengthening of the V1V2 amino-acid chain, and/or by adding 

carbohydrate moieties at N-linked glycosylation sites. The significance of the apparent 

increase in V1V2 length by calendar year is unclear but may be related to sampling bias. 

HIV-1 V1V2 loop length may be an indirect clinical indicator of humoral immune 

competence. Vaccines eliciting humoral immunity to HIV may provide greater protection 

from donors with early infection and shorter V1V2 loop lengths than from donors with 

chronic disease and longer V1V2 length variants. 


FP 1.5 

Generic Screening test for infection 

PLANTIER JC, LEMEE V, NABIAS R, SIRE JM, SIMON F 

CHU charles Nicolle - ROUEN- FRANCE Institut Pasteur- DAKAR - SENEGAL 

Background 

With the larger access to therapy in developing world, cheap, reliable and easy to perform 

assays for HIV screening and follow up are badly needed. 

Objective 

to propose a test to detect the anti-HIV antibodies for the serological screening and 

confirmation of HIV infection, highly sensitive and specific, cheap and easy to produce, 

applicable in countries with limited resources. 

Methods 

we evaluated in field condition a home-made EIA test to screen anti- HIV antibodies. 

Three peptides representing the immunodominant gp 41 transmembrane regions of 

HIV-1 groups M and O and HIV-2 were synthesized (NéoMPS, Strasbourg, France). 

An equimolar mixture of these peptides to a final concentration of 1.9 µg/mL was used for 

microplates coating. EIA were performed as usual with three washing steps followed by 

anti-human IgG conjugate labeling. Field evaluation was performed on 1230 negative and 

223 positive African samples. Results were compared to those obtain in a highly 

sensitive and specific commercial assay (AXsym HIV1/2gO automat, Abbott, Chicago, Ill.). 

The negative panel corresponded to patients attending to the blood bank in Dakar, 

Senegal. The positive panel corresponded to samples previously confirmed HIV by 

Western blotting and sequenced: 201 HIV-1 group M samples (subtype B and non-B), 

5 group O, 15 HIV-2, and 2 HIV-1/HIV-2 dual-infection. 

Results 

three of the 1230 (0.2%) negative samples were found repeatedly above the cut-off and 

confirmed as false positive results. One positive sample (0.4%) was not detected by the 

test. This sample was collected during the "window period" during HIV-1 primary 

infection. The HIV variants, particularly the highly divergent group O samples and HIV-2 

were detected. 

Conclusion 

This generic test, easy to produce including in developing countries, shows high 

performances on this large panel, all variants being detected. This simple and cheap 

assay can be used for large-scale screening in limited resources countries. Furthermore, 

the WHO in its strategy for HIV diagnosis recommends the use of successive tests based 

on different format and antigens for HIV-infection confirmation. The good specificity of our 

EIA based on peptidic antigens can be useful in this strategy. 



FP 1.6 

Analysis of plasma cytokines in Immunological and virological discordant HIV-1 

infected patients by Microarray system: A pilot study. 

Naresh Sachdeva 1 , H S Yoon 1 , Kyoko Oshima 1 , Luis Cintron 2 , Domingo Garcia 2 , 

Karl Goodkin 1 and Deshratn Asthana 1 . 

1 

University of Miami and 2Borinquen Health care Center, Florida, USA. 

Background and Objectives 

There are some HIV infected patients in whom complete suppression of the viral load 

does not assure restoration of CD4+ T cell counts. Such discordant responses suggest 

that there are other factors in immune system that influence the restoration of CD4+ T cell 

numbers despite changes in the plasma HIV-1 levels. It is well established that the 

combined effect of multiple cytokines and chemokines in the immune response to 

disease or immune modulation by drugs is often more important than the function of 

specific cytokines. Therefore, the plasma cytokine milieu might be significant in influencing 

the immune response to HIV-1 during the course of infection. In this study we have used 

a commercially available biochip microarray system capable of measuring 12 cytokines 

(IL-2, IL-4, IL-6, IL-8, IL-10, IL-1α, IL-1ß, IFN-γ, TNF-α, MCP-1, VEGF, and EGF) in 

Immunological and virological discordant HIV-1 infected subjects to find out differences if 

any in their cytokine profiles compared to concordant HIV-1 infected individuals. 

Methods 

EDTA plasma samples were obtained from 25 discordant, 25 concordant HIV patients and 

12 normal healthy individuals. A sandwich chemiluminescent assay was performed with 

100 µl of plasma sample using reagents (including the calibrators and controls) and 

protocols supplied by the same manufacturer. Cytokine levels between study subjects 

were compared by paired samples t- tests using SPSS software (version 3.0). 

Results 

Overall there appeared to be a significant difference in the levels of TNF-α, MCP-1 and 

EGF between the patients versus the normal healthy controls (p

FP 1.7 

HIV-1 Subtype C Viruses Rapidly Develop K65R Resistance to Tenofovir 

in Cell Culture 

Mark A. Wainberg and Bluma G. Brenner 

Centre sur le SIDA de l'Université McGill, Hopital Juif de Montréal 

Background 

Genotypic diversity among HIV-1 subtypes and circulating recombinant forms (CRFs) may 

lead to distinct pathways to drug resistance. This study evaluated subtype-related differences 

in the development of resistance in culture to tenofovir (TDF). 

Methods 

Genotyping determined nucleotide diversity among subtypes. Representative subtype B, 

C, CRF01_AE, CRF02_AG, G, and HIV-2 isolates were selected for resistance to TDF, 

lamivudine (3TC) and didanosine (ddI) in cell culture. Phenotypic assays determined the 

effects of the K65R substitution in reverse transcriptase (RT) on drug susceptibility. 

Results 

Subtype C isolates show unique polymorphisms in RT codons 64 (AAG→AAA), 65 

(AAA→AAG), and 66 (AAA→AAG), absent in other subtypes. The K65R mutation 

(AAG→AGG) arose with TDF by week 12 in four subtype C selections. In contrast, no TDF 

resistance arose in four subtype B (>34-74 wks), one each of CRF2 and G (>30-33 wks), 

and three HIV-2 (>27-28 wks) selections. K65R appeared after 55 and 73 weeks in two 

CRF1 selections with TDF. In contrast, times to appearance of M184V with 3TC pressure 

(weeks 8-14) did not vary among subtypes. Selective ddI pressure resulted in the 

appearance of M184V and L74V after 38 weeks in 2 of 4 subtype C selections. The K65R 

transitions in subtype C and other subtypes (AGG and AGA) conferred similar 4-10 fold 

resistance to TDF and 5-40 fold cross-resistance to each of abacavir, 3TC, and ddI, while 

not affecting zidovudine susceptibility. 

Conclusions 

TDF-based regimens will need to be carefully monitored in subtype C infections for 

possible selection of K65R. 



FP 1.8 

Detection of low frequency HIV-1C drug resistant variants in treatment 

exposed patients 

Harriet Okatch, Vlad Novitsky, Awo Osafo-Addo,Max Essex 

Harvard Scool of Public Health651 Huntington av, Boston, MA, 02115 

The monitoring of development and transmission of drug resistant HIV-1 is of importance 

especially for optimization of treatment strategies. However, conventional methods for 

genotypic analyses only allows detection of viral strains if they exist at greater than 30 % 

of the viral population. However, low frequency variants may be predictors of failure of 

antiretroviral therapy and therefore, their prevalence should be determined in patients 

receiving treatment. The aim of this study is to detect low frequency viral variants in 

HIV-1C infected patients by single genome sequencing 1 . This study utilizes samples from 

a longitudinal study in which patients are followed every two months for a period of 

thirty-six months. At each visit, CD4 and plasma viral load is monitored. Bulk sequencing 

of plasma RNA is carried out when patients experience virological failure. The method 

employed, determines proviral load by real time PCR, after which, the sample is diluted to 

contain one DNA copy per 5 µl. Nested PCR's are carried out and 20 sequences 

generated per time points prior to time point when virological failure is observed.Drug 

resistant variants were successfully detected in proviral DNA four months earlier than 

virological failure is observed. The method employed also detected viral mutants that had 

been missed by the conventional bulk sequencing and detected viral variants that were 

present at as low as 5%. Although the full clinical significance is undetermined, the ability 

to detect drug resistant mutations at earlier time points than conventional bulk sequencing 

can lead to intervention of treatment and allow for optimization of treatment strategies. 

The presence of low frequency viral variants can be used as predictors of virological 

failure. 

1.S. Palmer et al. Multiple, Linked Human Immunodeficiency Virus Type ! Drug Resistance 

Mutations in Treatment-Experienced Patients Are Missed by Standard Genotype Analysis. 

J. Clin. Microbiol., 2005; 43(1) 406-413. 


FP 1.9 

HCV-Associated B cell Clonalities in the Liver do not carry the t(14;18) 

Chromosomal Translocation 

Domenico Sansonno, Felicia Anna Tucci, 1 Valli De Re,Gianfranco Lauletta, Michele 

Montrone,1Massimo Libra,Sansonno Loredana, Franco Dammacco 

DEPARTMENT OF INTERNAL MEDICINE AND CLINICAL ONCOLOGY, UNIVERSITY 

OF BARI MEDICAL SCHOOL, POLICLINICO, PIAZZA GIULIO CESARE 11 70124 BARI, 

ITALY.1Division of Experimental Oncology I, Centro di Riferimento Oncologico, Aviano 

(PN), Italy 

Hepatitis C virus (HCV), a positive-strand enveloped RNA virus belonging to the 

Flaviviridae family, genus Hepacivirus, causes acute and chronic liver damage. The 

mechanisms responsible for the tissue injury are poorly understood. HCV often leads to 

hepatocellular carcinoma (HCC) and, less frequently, to B-cell non-Hodgkin's lymphoma 

(B-NHL. HCV is mainly characterized by the failure to generate an effective immune 

response. Derangement of the B cell immune response has recently been explored by 

analyses of the size and sequence of complementarity determining region-3 (CDR-3) in 

the variable diversity joining (VDJ) segment of immunoglobulin heavy chain (IgH), which 

provide a molecular footprint of the overall B cell receptor (BCR) repertoire. Chromosomal 

translocation t(14;18) involving Bcl-2 oncogene has been reported in circulating B 

lymphocytes of HCV-infected patients, suggesting that HCV may cause chromosomal 

instability. In t(14; 18) translocation, Bcl-2 gene (chr 18) comes to lie 5' to the IgH (chr 14) 

J region (Bcl-2/JH), resulting in overexpression of Bcl-2 protein. This translocation has 

frequently been reported in peripheral blood mononuclear cells (PBMCs) in HCV-related 

mixed cryoglobulinemia (MC), a chronic, indolent lymphoproliferative disorder with 

potential progression towards B-cell NHL. PCR amplification assays for Bcl-2/IgH 

rearrangement were performed on nucleic acids extracted from portal tract inflammatory 

infiltrates, isolated with laser capture microdissection (LCM) from liver biopsy sections of 

16 HCV-infected patients with and without extrahepatic B cell-related disorders. 

Results were compared with total DNA extracted from core liver biopsy specimens and 

from peripheral blood mononuclear cells (PBMCs). We failed to demonstrate specific 

Bcl-2/IgH amplicons either in liver tissue or in PBMCs in all patients of the present series. 

Multiplex PCR assays for variable diversity joining (VDJ) IgH gene rearrangements were 

also carried out in the liver compartment. Selective amplification compatible with mono or 

oligoclonal B cell clonotypes was demonstrated in 80% (6/8) and 25% (2/8) of patients 

with and without clinical evidence of B-cell disorders. V H 1 and V H 3 were the most 

represented V H families. In situ expression of Bcl-2 protein was carried out by 

immunohistochemistry on liver biopsy sections. Bcl-2 protein was detected in 2 (12.5%) 

patients who did not associate extrahepatic disorders. In conclusion, present data support 

the concept that production of IgH gene rearrangements is not associated with Bcl-2/IgH 

chromosomal translocation in hepatic compartment and that liver overexpression of Bcl-2 

protein may occur in at least a minor proportion of HCV-infected patients. 



FP 1.10 

Replication-Competent Platforms for Lassa Fever Vaccine Design 

Lukashevich IS 1 , Moshkoff D 1 , Patterson J 2 , Carrion R 2 , Bredenbeek P 3 , Spaan WJM 3 , 

Salvato MS 1 

1 

Institute of Human Virology, University of Maryland, Baltimore, MD, USA; 

2 

Southwest Foundation for Biomedical Research, San Antonio, TX, USA; 

3 

Leiden University Medical Center, Leiden, The Netherlands 

Objectives 

Lassa (LAS) fever is a serious medical problem in West Africa. The sizeable disease 

burden and the possibility that LAS virus can be used as an agent of biological warfare 

make a strong case for vaccine development. Replication-competent vaccines elicit strong 

cellular immune responses, confer long-term protection after a single injection, and have 

low manufacturing costs. These features make live vaccines are very attractive 

alternatives for African countries. 

Methods 

1. Reassortant technology was used to make reassortants between LAS and Mopeia 

(MOP) virus, a non-pathogenic close relative of LAS. Clone ML29, selected from a library 

of MOP/LAS reassortants, encodes the major antigens (NP and GPC) of LAS and the 

replication machinery of MOP. 2. The full-length infectious cDNA clone of the vaccine 

strain of Yellow Fever (17D) has been used to design the second vaccine candidate, 

recombinant YF17D/LAS-GPC. LAS GPC gene was cloned and expressed in frame 

between E and NS1 genes of YF17D. 

Results 

1. Replication of ML29 was attenuated in guinea pigs and nonhuman primates. The ML29- 

vaccinated animals were fully protected not only against challenge with homologous virus, 

LAS-JOS, but also against distantly-related LAS-NIG isolate. Simultaneous replication of 

ML29 and LAS in vaccinated/challenged animals attenuated wild-type LAS infection. 

2. The recombinant YF17D/LAS-GPC replicated poorly in guinea pigs but still elicited 

specific antibodies against LAS and YF17D antigens. A single vaccination with the 

recombinant virus protected 80% guinea pigs against heterologous challenge. 

Conclusion 

Both viruses, clone ML29 and recombinant YF17D/LAS-GPC, are promising vaccine 

candidates for LAS fever. 


FP 1.11 

Bats as potential reservoirs for Ebola virus 

Pourrut Xavier, Leroy Eric 

IRD(UR178)/CIRMF Franceville, GABON 

Ebola virus (EBOV), together with Marburg virus, belongs to the Filoviridae family, a group 

of enveloped, non-segmented, negative-strand RNA viruses. EBOV includes three 

subtypes in Africa (Sudan ebolavirus, Zaïre ebolavirus, Ivory Coast ebolavirus) and one in 

Asia (Reston ebolavirus). Ebola causes severe hemorrhagic fever in humans and great 

apes. The human case-fatality rate is about 80% for the Ebola Zaire subtype (EBOV-Z), 

which is the most pathogenic one. Accidental transmission of the disease to humans 

occurs by direct contact with infected dead animals, mainly chimpanzees and gorillas. 

Great apes are very vulnerable to infection by EBOV-Z. It has been estimated that 50 to 

80 % of chimpanzee and gorilla populations disappeared during previous outbreaks in 

affected regions of Republic of Congo (RC) and Gabon. The lack of identity in the 

glycoprotein (GP) sequences detected from different animal carcasses suggests that 

infection of great apes resulted from simultaneous but independent transmission events 

from the reservoir species. Over the past 30 years, the natural reservoir for Ebola 

remained a mystery, despite intensive efforts to identify it. Recently however, we showed 

for the first time that some fruit bat specimens were asymptomatically infected with 

EBOV-Z. During the outbreaks in Gabon in 2001 and RC in 2003, 1030 animals were 

captured and tested for the virus, including 679 bats, 222 birds and 129 small terrestrial 

vertebrates. Evidence for EBOV was found only in bats. Specific antibodies (IgG) for 

Ebola virus were detected in serum from three different frugivorous bat species, 

Hypsignathus monstrosus (4/17), Epomops franqueti (8/117), Myonycteris torquata (4/58). 

Viral nucleotide sequences were detected by PCR in organs of the same species (4/21 in 

H.m., 5/117 in E.f., and 4/141 in M.t.). These results strongly suggested that these bat 

species are a natural EBOV reservoir, although other animal species may also be 

involved. The next step will be to understand how bats can transmit EBOV to great apes. 

EBOV outbreaks mainly occur during the end of the dry season, which is birthing season 

for bats. At this time of year, fruit is scarce in the forest and this may lead bats and gorillas 

to forage in the same trees for food. EBOV transmission to great apes may occur directly 

through infected fluids such as saliva, blood or foetal envelopes. In Asia, bats are the 

reservoir for two viruses, Nipah and Hendra, both of which belong to Paramyxoviridae, a 

virus family that shares strong genetic similarities with the Filoviridae. Viral transmission 

from bats to vulnerable species (pigs and horses) can occur either by saliva (Nipah) or by 

placenta (Hendra).A better understanding of viral transmission from bats may help to 

develop strategies to prevent Ebola outbreaks in great apes and humans. 



FP 2.1 

Long-term non-progression in HIV infection: Experience of the Australian cohort. 

Linda Gelgor, Tony Kelleher, John Kaldor*, National Centre in HIV Epidemiology and 

Clinical Research, University of New South Wales, Sydney, Australia. 

Background 

Before effective treatments became available for HIV infection, it was recognised that 

progression to AIDS was virtually inevitable, with a median time of 8-10 years. However, 

a small group of people seemed to be more resistant to progression, and became a focus 

of interest for investigation of viral and host factors. 

Methods 

A cohort was recruited mainly through primary health clinics in 1994-5, of people who had 

documented HIV infection of at least 8 years duration, and whose CD4 count remained 

repeatably above 500//µl. This cohort was followed clinically on an annual basis, with 

specimen storage and regular recording of CD4 counts, viral load, clinical disease and 

therapeutic intervention. A number of other specialised analyses were also undertaken, 

including T-cell receptor polymorphisms, HLA typing, and viral sequencing. A series of 

publication on the cohort over the past ten years demonstrated associations at baseline 

with heterozygosity for CCR5?32, and several HLA alleles that had been previously 

associated with slower progression. A small number of cohort member were also found to 

have nef deleted virus. We continued follow up of the cohort and analysed the most recent 

outcomes. 

Results 

A total of 110 people were recruited into the cohort as long-term non-progressors, of whom 

23 have been lost to follow up (no information within the past 3 years), 3 have been 

recorded has having died, 8 developed AIDS and 39 commenced antiretroviral treatment 

but were not recorded as having AIDS. Of the remaining cohort members, there were 28 

(25%) whose most recent CD4 count was above 500/ µl, and 21 (19%) whose most recent 

viral load was below 5000 copies/ µl. The median duration of follow up in this subgroup 

was 8 years from enrolment, giving a total median duration of known infection of 16 years. 

Comment 

This study demonstrates the existence of a phenomenon of HIV control that is sustained 

in a substantial proportion of the cohort. Initially recruited on the basis of immunological 

preservation, a fifth of the cohort has demonstrated ongoing viral control. This 

phenomenon is not explained in the cohort by known genetic polymorphisms or viral 

mutations. It is obvious yet no less true to note that there is much more that we can learn 

about long-term non-progression, and its implications for vaccines and therapy 


FP 2.2 

HIV-1 and HIV-2 DNA in the early phase of infection : in vitro quantification by real 

time PCR using a combined HIV-1+ HIV-2 plasmid 

Marie Gueudin, Jean-Christophe Plantier, Joséphine Braun, Florence Damond, and 

François Simon 

CHU Charles Nicolle - ROUEN CHU Bichat - PARIS 

Background-Objective 

HIV-2 plasma viral loads are significantly lower than those found in HIV-1 infection. Our 

objective was to study the in vitro replication of HIV-1 and HIV-2 during the early stage of 

infection. 

Methods 

To quantify HIV-1 and HIV-2 DNA production during the early phase of in vitro infection, 

we produced a plasmid integrating both HIV-1 and HIV-2 DNA. Two fragments of the LTR 

of HIV type 1 and type 2 were linked using overlapping common primers and integrated 

in a pCR 2.1-TOPO plasmid. TCID50 of HIV-1 NL4-3 and HIV-2 ROD supernatants used 

for inoculation were determined and cells were infected with 500 TCID50 of HIV-1 NL4-3 

or with 500 TCID50 of HIV-2 ROD. Cultures were performed onto PBMC from 3 different 

blood donors and onto MT4 -CXCR4 and Hela-P4-CCR5 cells lines. Post transcriptional 

viral production was inhibited by saquinavir and DNA production kinetics were assessed 

at 6, 12, 24 and 72 hours post infection. HIV-1 and HIV-2 DNA was quantified by real-time 

PCR using the HIV-1 and HIV-2 plasmid as a standard. Results were expressed in Log of 

HIV DNA copies/µg of total DNA extracted. 

Results 

Despite equivalent infectious doses, major differences in DNA production were recorded 

between the both HIV types. At 6H post infection, whatever the cells, the quantity of DNA 

obtained with HIV-2 ROD (2.0 log) was 2 Log lower than the quantity obtained with HIV-1 

NL4-3 (4.0 Log). This sharp difference has been observed throughout the kinetic study 

despite a weak HIV-2 DNA increase at 24 -72H. These results were independent from the 

PBMC donors. Results were strictly similar onto MT4-P which does not express the 

co-receptor CCR5 and on the cells line HeLa-P4-CCR5 which expressed both the CCR5 

and the CXCR4. 

Conclusions 

We observed in vitro major differences between HIV-1 and HIV-2 DNA production during 

the early stage of infection. Real time PCR quantification based on a single plasmid 

harbouring HIV-1 and HIV-2 sequences allows us a perfect comparison between the 2 HIV 

types, avoiding artificial differences in amplification. DNA synthesized depends of the HIV 

RNA availability in the cell and/or of the efficiency of the reverse transcription of this viral 

RNA. Our experiment does not allow us to determine if only one or the two stages are 

deficient for HIV-2 but it gives a serious track to explain most completely the 

physiopathology of the infection. 



FP 2.3 

HAART in Sub-Saharan countries. The panacea? 

Christian Viladent, Ann van Ackere 

HEC Lausanne, University of Lausanne 1015 Lausanne Switzerland 

Objective Highly active antiretroviral therapy (HAART) have been recently introduced in 

the sub-Saharan region, the aim of the present work is to assess the impact of HAART 

and other interventions on the HIV/AIDS epidemic thanks to a deterministic compartmental 

simulation model. Model description The model consists of four population groups, each 

group includes five age-classes • Two non-core groups of male and female individuals 

from the general population • One core group: the female sex workers • One bridge 

group: the mobile workers (either miners or truckers) Each group includes susceptible and 

infected individuals. Infected individuals are divided into four disease stages according to 

WHO classification. The HIV contamination between the various populations groups are 

represented by matrixes. The model exhibits a user-friendly control panel which allows 

easy parameter changes, therefore, a quick appreciation of their consequences on 

HIV/AIDS propagation and local socio-economic factors. The model is calibrated with data 

from Botswana. Various scenarios have been tested as shown in table 1 Scenarios # Type 

of intervention Base case New patients on HAART at the current implementation rate 

(approximately 15,000 new patients per year) 1 New patients on HAART at double 

implementation rate (30,000 new patients per year) 2 Increased condom usage from 30 

to 50% and from 20 to 40% usage for the two male age class 15-24 and 25-49, 

respectively 3 Increased condom usage from 30 to 70% and from 20 to 60% usage for the 

two male age class 15-24 and 25-49, respectively 4 Reduction of risky sexual behaviors 

(50 reduction of casual relationships for each age class for both male and female) 5 

Reduction of risky sexual behaviors (50% reduction of concurrent relationships in each 

age class for male and female), other conditions similar to the base case 6 Reduction of 

STDs (from 30 to 15%), other conditions similar to the base case 7 Reduction of STDs 

(from 30 to 15%) without HAART Table 1: Scenarios tested . Results We measured the 

efficiency of each scenario by comparing the cumulated number of deaths avoided from 

AIDS in 2010 thanks to the intervention versus the death from AIDS with no intervention. 

We found that the most efficient scenario consist in reducing the STDs (from 30% to 15%) 

in association with HAART therapy at the current implementation rate. The second most 

efficient scenario consists in doubling the HAART implementation rate. Although this 

scenario is efficient in term of lives saved, it also leads to an increase of the number of 

infected individuals compared to the base case. Conclusion The preliminary model 

outputs show that HAART alone, at the current implementation level, although showing 

some efficiency, cannot significantly impact the number of HIV/AIDS infected individuals 

in the long term. Among the five scenarios tested, the association of HAART with the cure 

of other sexually transmitted diseases (STDs) seems to be more promising and could 

potentially cut the number of infected individuals in Botswana by half, by 2010. 


FP 2.4 

Stigmatization and adherence to HAART among two cohorts of HIV positive patients 

in Bamako and Ouagadougou 

Ngamini Ngui A.(1), Zunzunegui M.V.(1,2),Boileau C.(1,2), Ag Aboubacrine S.(2), Niamba 

P.(2), Sylla M.(2), Rashed S. (1,2), Nguyen V.K.(2) 

(1) University of Montreal, Département de Médecine Sociale et préventive(2) Pro-ARV 

group 

Objectives 

The objective of the present study is to describe stigmatization among Persons living with 

the HIV (PlHIV) and to examine links between the adhesion to treatment of Antiretroviral 

Therapy (ART) among the PlHIV and the stigmatization. 

Methods 

649 patients receiving ART of which 322 in Bamako and 327 in Ouagadougou were 

interviewed on their behaviour in adhesion to treatments. Adhesion was measured with 

the number of tablets taken by the patient for the last seven days precedent the inquiry. 

To be considered a member, a patient must have set regularly and without any 

interruption, all the tablets prescribe by the doctor. An explanatory factorial analysis of a 

list of 13 items allowed building a scale of measure of the stigmatization regrouping 7 

items. The coefficient of reliability was estimated. Variable associated in the stigmatization 

were identified and a logistic regression was fitted to data to estimate the association 

between the stigmatization and the adherence to the treatment of ART. 

Results 

Altogether, 70 % of the patients are good adherent to ART (75 % in Bamako and 57.1 % 

in Ouagadougou, p < 0.01). Our study shows that with regard to those that are strongly 

stigmatized those that do not feel any feelings of stigmatization are more adherent (60.84 

% against 74.34 %, p < 0.05). The women, the young people, the persons discriminated 

on the material plan are more stigmatized than men, the older persons and the 

materially favoured persons. The association between the stigmatization and the 

adherence remains significant (OR=2.02 , 95 % IC=1.30-3.12) by controlling for the sex, 

the age, the schooling, the implication in the associations of persons living with the HIV, 

the self reported health and the quality of relations among the patient and his doctor. 

Conclusion 

stigmatization is more felt at the most vulnerable layers of population. Furthermore, 

stigmatization appears as a major obstacle to a good adherence to the treatments of ART 

among the PlHIV. It would be so important to fight it if one wants to succeed in the 

policies of fight against the HIV / AIDS. 



FP 2.5 

Morbidity and mortality by baseline CD4 cell count during the first months following 

HAART initiation in HIV-infected adults in Abidjan, Côte d'Ivoire 

Raoul Moh 1 , Christine Danel 1 , Albert Minga 1 , Amani Anzian 1 , Olivier Ba-Gomis2, 

Jonas Séri 3, Gustave Nzunetu 4 , Delphine Gabillard 5 , Souleymane Sorho 1 , 

Emmanuel Bissagnéné 4 , Roger Salamon 5 , Serge Eholié 4 , Xavier Anglaret 5 , 

and the Trivacan ANRS 1269 trial team 

1 

Programme PACCI, Abidjan, Côte d'Ivoire 

2 

Centre de Diagnostic et de recherches sur le SIDA (CIRBA), CHU de Treichville, Abidjan 

3 

Unité de soins Ambulatoires et de Conseils 

4Service des Maladies infectieuses et Tropicales, CHU de Treichville, Abidjan 5INSERM 

U.593 , Université Victor Segalen Bordeaux 2, Bordeaux, France 

Objectives: To estimate the incidence of severe morbidity and mortality by baseline CD 4 

cell count in sub-Saharan African HIV-infected adults during the first months following the 

initiation of highly active antiretroviral therapy (HAART). 

Methods: HAART-naïve HIV-infected adults were included in the pre-randomisation phase 

of a randomised controlled trial of structured treatment interruption (STI) in Abidjan. The 

main inclusion criterion was a CD 4 count at 150-350/mm 3 or a CD 4 percentage at 

12.5%- 20%. After inclusion, participants received a continuous HAART. Those patients 

with criteria for HAART success after at least 6 and at most 18 months of continuous 

HAART in the pre-randomised phase were randomised into the STI trial. We report here 

mortality and severe morbidity under continuous HAART during the pre-randomisation 

phase. Severe morbidity was defined as any WHO stage 3 or 4-defining morbidity. 

Results: From December 2002 to April 2004, 840 patients (76 % women, median age 34 

years, baseline CD4 < 200/mm 3 :29%, at 200-350/mm 3 :52% and > 350/mm 3 : 18%) started 

either ZDV-3TC-EFV (88%) or ZDV-3TC-IDV/r (12%). The median follow-up on 

continuous HAART is the pre-randomisation phase was 8.1 months (interquartile range 

[IQR] 7.1;13.4). 2% of patients were lost-to-follow-up. In patients with baseline 

CD4≥350/mm 3 , 200-350/mm 3 , and

Conclusion: In this cohort of West African adults who participated in the pre-randomisation 

phase of a STI trial and who thus started HAART at early stage of immunosuppression, 

the rate of severe morbidity during the first months following HAART initiation was higher 

than expected, including in patients with baseline CD4 > 350/mm 3 . We were not able to 

estimate which proportion of severe morbidity was associated with the immune 

reconstitution syndrome. The hypothesis that HAART should be started earlier in 

sub-Saharan Africa than in industrialized countries because of specific spectrum of early 

morbidity deserves further consideration. 



FP 2.6 

Tolerability of antiretroviral drugs used in post exposure prophylaxis after sexual 

assault in the Cape Metropole region 

P.Mugabo 

Department of Pharmacology, University of the Western Cape, Cape Town, South Africa. 

Objectives 

Zidovudine and lamivudine are used in post exposure prophylactic (PEP) treatment after 

rape. The major problems experienced in the management of HIV in rape survivors is the 

low rate of response to follow-up visits. The aim of this study was to determine the safety 

and tolerability of the antiretroviral drugs used in PEP and to find out whether the 

intolerability could explain the poor follow - up rate. 

Methods 

The study was designed as a retrospective and prospective survey involving female rape 

survivors randomly selected from the register of rape victims recorded in 2004 and 2005 

at Karl Bremer Hospital. 150 survivors were retrospectively surveyed and 100 survivors 

were prospectively followed up. Descriptive, quantitative statistical methods were used for 

assessment of the data. Informed written consent was obtained from each survivor 

involved in the study. 

Results 

The ages of the victims range between 1 and 60 years. Of the survivors interviewed, 77% 

had taken the medication as prescribed; of these 63% completed treatment and 37% did 

not. The reasons for not completing the course of medication included: too many tablets 

to take (2%), felt sick (2%), perceived medicines as toxic (5%), did not return to hospital 

for balance of medicine (25%), forgot medication at home while on a trip (2%) and side 

effects (64%).The main side effects experienced are nervousness and anxiety (33%), 

nausea (65%), vomiting (31%), fatigue (33.5%), bloating or gas in the stomach (53.7%), 

abdominal cramps (19%), loss of appetite (55%), depression (sadness) (26%), insomnia 

(24%), dizziness (19.3%), muscle aches and/or joint pain (15.3%), difficulty in 

remembering (11%), headache (12%), fever, chills and sweats (10.5%). 

Conclusion 

This study explains why rape victims did not attend follow up visits. Side effects are the 

major cause. More rape survivors should be involved in this study for more conclusive 

results. 

Acknowledgment: 

I wish to acknowledge the University of the Western Cape for financial support of the 

project. 


FP 2.7 

Hepatic steatosis in HIV and Hepatitis C virus coinfected patients receiving 

antiretroviral therapy 

MARTINEZ V. 1 , TA TDN.1, MOKHTARI Z. 1 , GUIGUET M. 2 , VALANTIN MA. 1 , 

CHARLOTTE F. 3 , BENHAMOU Y. 4 , CAUMES E. 1 , BRICAIRE F. 1 , KATLAMA C. 1 

1. 

Department of Infectious Diseases 

2. 

INSERM U7203. Anatomopathology4. HépatologyHôpital Pitié-Salpêtrière, 75013 Paris, 

France 

Background 

To evaluate prevalence, severity of hepatic steatosis and to assess risk factors influencing 

hepatic steatosis in HIV/HCV patients taking antiretroviral therapy (ART). 

Methods 

A retrospective study was conducted on HIV/HCV patients treated by ART, who underwent 

liver biopsies from january 1995 to june 2005. All patients were negative for HBV testing 

and never been treated for HCV. All liver biopsies were read by the same pathologist. 

Hepatic steatosis was graded according to the percentage of hepatocytes affected: 

0, none;1, steatosis involving 66%. Demographics and 

laboratory parameters were recorded at time of hepatic biopsy. 

Results 

127 HIV/HCV coinfected patients were included. Median age was 39 years (35-43), 82% 

were male, 89% were Caucasian, 78% had a past history of IV drug abuse.At the time of 

biopsy, HIV viral load was suppressed (45 years, genotype 3 

and abacavir use remained associated with decreased risk of hepatic steatosis. 

Conclusion 

Hepatic steatosis was present in 62% of HIV-HCV coinfected patients receiving ART. 

In multivariate analysis, independent determinants of hepatic steatosis were 

age>45 years, genotype 3 and abacavir use remained associated with decreased risk of 

hepatic steatosis. Protective effect of abacavir, a non thymidinic drug group with less 

mitochondrial damage, underlines the possible key role of DNA mitochondrial toxicity in 

the genesis of steatosis and suggests opportunity to prevent hepatic steatosis in HIV and 

HCV coinfected patients. Nevertheless, the role of drug classes and drugs within classes 

should be investigated in prospective studies. 



FP 2.8 

Radata - An internet-based system for salvage patients with the possibility of expert 

advice 

Lorenzen T, Graefe K, Stoehr A, Hoffmann C, Plettenberg A 

ifi-Institute for Interdisciplinary Medicine, Hamburg, Germany 

Objective 

Failure of antiretroviral therapy (ART) is a complex area, which involves many factors such 

as resistances, drug levels and patients adherence. The Radata-system considers these 

aspects. A further option of this cohort is the possibility to obtain expert advice to support 

therapeutic decisions via internet. 

Methods 

Patients may be included while in need of a new ART due to increased viral load or 

toxicity. Radata collects demographic data, informations concerning medical history, 

current lab results, patients opinion and requirements to future ART and course of 

disease. Depending on physicians choice, laboratories are informed about upcoming 

resistance analysis (RA) or therapeutic drugmonitoring (TDM). Experts may review the 

data online and perform their recommendation. All data entries are directly entered online 

into the database. 

Results 

Since 2002, 593 patients out of 75 centers have been included in the Radata-Cohort. 498 

RA and 462 TDM are available. Expert advice has been performed in 435 patients. For 

383 patients ART-switch is documented. To date, median observation time for all patients 

is 9 months, maximum 33 months. Median number of ART regimens prior to recruitment 

was 6, time since first ART initiation was 90 months. Patients had in median 6 reverse 

transcriptase and 4 protease resistance mutations. Experts recommended in median 

4 antiretroviral substances (Ritonavir booster excluded) and physicians utilised 

recommendations in most cases. 12 month follow up showed median viral load decrease 

of 0.3 log10 and CD4 increase of 28 c/µl. 

Conclusions 

The Radata-Cohort was initiated 2002. The aim was a better understanding of 

mechanisms of therapeutic failure in HIV-infected patients. Therefore an internet-based 

system was developed to collect data of different specialities involved in ART-decisions. 

Patients included are heavily pretreated and have very limited options for future therapies. 

Nevertheless viral load and CD4-cell counts improved slightly over 12 months. 


FP 3.1 

An HIV-1 peptide-based vaccine inducing cross-subtype immunity in macaques 

F.Diaz-Mitoma 1,2 , D.E. Anderson 1 , A.Azizi1, 2 , M.Ghorbani 1,2 , C.Soare 1,2 , A.Ogrel 1 , 

S.Aucoin 1,2 , R.Frost 1,2 , S.Ogrel 1 , and J.V.Torres 1 

1 

Variation Biotechnologies, Inc., 22 de Varennes, Suite 210, Gatineau, QC, CANADA; 

2 

Children's Hospital of Eastern Ontario, Regional Virology Laboratory, Ottawa, ON, CANA- 

DA 

Background 

The unprecedented rate of mutation of HIV-1 and resulting antigenic heterogeneity among 

the HIV viruses circulating throughout the world poses a significant challenge to vaccine 

development. This study measures the immune response to a peptide-based vaccine 

against variable regions of HIV with the belief that these regions represent areas in which 

the virus is susceptible to immune recognition and elimination. We have synthesized and 

evaluated the immunogenicity of a vaccine that contains a total of 176 lipidated and 

non-lipidated peptide variants that represent 7 antigenically variable regions of the Env 

and Gag proteins of HIV-1. 

Objectives 

To evaluate a vaccine strategy that targets only antigenically variable regions of HIV-1 Env 

and Gag and to measure cellular immunity induced by the vaccine candidates. 

Results 

All animals had cellular immunity to naturally processed viral antigens. 3/6 animals had T 

helper cell responses to Env proteins from multiple, divergent subtypes of HIV-1 (B, C, and 

E); two additional animals recognized multiple distinct subtype B variants of HIV-1. 

All animals had activated CD8+ T cells, measured both by intracellular IFN-g staining and 

ELISPOT, that recognized naturally processed epitopes delivered by vaccinia constructs 

encoding Env and Env/Gag/Pol proteins from multiple, divergent subtypes of HIV 

(A, B, C, D, E. and F). Noteworthy was the ability of sera from one animal to neutralize 

multiple, primary, T cell tropic isolates of HIV-1 (30% of the isolates tested). Vaccination of 

HLA A*0201 transgenic mice with vaccine, followed by challenge with a recombinant 

vaccinia vector expressing Env/Gag/Pol from a clade E strain of virus, resulted in a 

two-log reduction in viral titers. 

Conclusions 

Our strategy is based on the belief that infection of humans with HIV-1 results in 

immunity that while rarely protective, nonetheless creates strong negative pressure on 

viral replication in vivo manifested as antigenic variation. This vaccine approach differs 

starkly from current vaccine strategies that target conserved epitopes to achieve 

cross-subtype immunological recognition of HIV-1. 



FP 3.2 

Glycosylated recombinant simian IL-7 induces sustained increased in peripheral 

naïve and memory T cell counts in healthy Rhesus macaques: a new possibility for 

immune reconstitution 

Stéphanie Beq, Clémentine Shilte, David Gautier, Xavier Montagutelli, Pascal Lavedan, 

Michel Brahic and Rémi Cheynier 

Institut Pasteur, Paris, France 

IL-7 is a crucial cytokine for both thymopoiesis and peripheral T cell homeostasis. Treating 

SIV-infected and non-infected macaques with RmIL-7 leads to a transient increase of 

circulating T cells, due to both enhanced thymopoiesis and increased peripheral T cell 

proliferation. However, the effect of non-glycosylated IL-7 is systematically blunted by the 

rapid development of a strong neutralizing anti-IL-7 immune response. In this study, we 

investigated the impact of a single dose (100 µg/kg) of glycosylated recombinant simian 

IL-7 (RmIL-7gly) on T cell homeostasis in healthy Rhesus macaques. Using 8 parameters 

flow cytometry and real time PCR for the quantification of the signal joint T cell receptor 

excision circle (sjTREC), we followed the frequency and the absolute numbers as well as 

the cycling and the survival capacity of the different peripheral T cell subsets : CD4, CD8, 

naives, memory, effector and recent thymic emigrants (RTEs, as defined by high 

expression of CD31 in naïve CD4 T cell subset and sjTREC frequency) during the first 

days following RmIL-7gly injection. Within the first 24 hours following RmIL-7gly injection 

we observed a strong decline of all T cell subsets in both CD4 and CD8 compartments. 

The analysis of T cell subsets in lymph nodes suggests that this decrease was a 

consequence of T cell homing into secondary lymphoid organs. Following this initial 

period, all T cell subsets demonstrate a strong expression of Ki-67 (30 to 90%). 

This proliferation leads to an expansion of the T cell subpopulations by day 4-7, reaching 

higher values than in pre-treatment samples. Finally, the absolute number of circulating 

RTEs began to increase by day 7, leading to a 5- to 10-fold increase at day 14 post 

RmIL-7gly. This was confirmed by the quantification of the sjTREC molecule in peripheral 

blood of the animals. A second injection in the same animals was performed 3 months 

after the first one. Similar modifications of peripheral T cell homeostasis were observed. 

Finally, contrarily to the non glycosylated molecule, RmIL-7gly did not induce the 

development of IL-7 specific antibodies. The administration of a single dose of RmIL-7gly 

both stimulates thymic function leading to enhanced RTE frequency and induces an 

increase of peripheral naïve and memory subset numbers in healthy Rhesus macaques, 

suggesting that HuIL-7gly might be used to help HIV-infected patients to recover from 

lymphopenia under efficient antiretroviral therapy. 


FP 3.3 

Effect of oligonucleotide adjuvant on the immune modulation induced by HIV-1 

whole inactivated vaccine in antiretroviral naïve HIV-1 infected patients 

Andrea Gori 1 , Daria Trabattoni 2 , Giuliano Rizzardini 3 , Renato Maserati 4 , 

Francesco Mazzotta 5 , Richard Bartholomew 7 , Georgia Theofan 7 , Dorothy H. Bray 8 , 

Mario Clerici 2 

1 

Institute of Infectious Diseases, and 

2 

Chair of Immunology, University of Milano, Milano, 

3 

Clinic of Infectious Diseases "L. Sacco" Hospital, Milano, Italy; 

4 

Department of Infectious Diseases, Ospedale San Matteo IRCCS, Pavia, Italy; 

5 

Department of Infectious Diseases, Ospedale SS Annunziata. Florence, Italy; 

7 

The Immune Response Corporation, Carlsbad, CA 92008, USA, and 

8 

Medical Research Council Clinical Trials Unit, London, UK. 

Background 

Synthetic oligonucleotides containing immunostimulatory cytosine-guanine (CpG) 

dinucleotide motifs can enhance immune responses induced by vaccines. We examined 

whether Remune ® (whole inactivated, gp120-depleted HIV-1 antigen in IFA), 

co-formulated with a novel oligonucleotide immunostimulatory adjuvant, AmplivaxTM, 

(IR103 therapeutic vaccine), can be safely administered in antiretroviral naïve HIVinfected 

individuals. We also evaluated the effects of IR103 on immune system 

parameters. 

Methods 

Thirty two antiretroviral naïve HIV-infected individuals previously enrolled in a 28 week 

study of Remune ® vs. placebo were randomized into a rollover study to receive either 

Remune ® (N=15) or IR103, Remune ® formulated with Amplivax (0.5 mg) (N=17) every 

12 weeks for a total of 5 injections. Kinetics of changes in immune parameters are 

evaluated at multiple times during the study period. Data from the ongoing study, obtained 

at weeks 4 and 12 are presented herein. 

Results 

No safety issues were identified in any subjects through 12 weeks of evaluation. At week 

12 (after 1 injection) compared to baseline the main immunological effect observed was a 

skewing of the CD8 T cells towards the more mature, lytic subpopulations. Thus: 1) central 

memory (CCR7+/RA-) CD8 T lymphocytes were diminished both in Remune ® and 

IR103 groups; 2) effector memory (CCR7-/RA-) and terminally differentiated (CCR7-/RA+) 

CD8 T cells were augmented both in Remune ® and IR103 subjects. These changes tend 

to occur more rapidly in individuals receiving IR103 compared to Remune ® , as they are 

already evident at week 4. In addition, the magnitude of these effects appears to be 

greater in subjects receiving IR103 that had received Remune ® (vs. placebo) in the 

previous study. 

Conclusions 

These preliminary results suggest that Amplivax, an oligonucleotide immunostimulatory 

adjuvant, potentiates the immunomodulatory effects associated with Remune ® in antiretroviral 

naïve HIV-infected individuals. Because defective maturation of CD8 T cells is one of the 

main immunologic problems seen in HIV infection, these results could be of particular 

interest in the management of HIV infected individuals. Further follow up data are 

required to confirm these observations. 



FP 3.4 

Therapeutic Tat-Vaccination In Chronic HIV-Infection 

Daniel Zagury 1 , Hélène Le Buanec 1 , Patrick Larcier 1 , Arsene Burny 2 , Robert C. Gallo 3 

1 

Néovacs S.A., Université Pierre et Marie Curie, Paris, France 

2 

Université Libre de Bruxelles, Brussels, Belgium 

3 

Institute of Human Virology, University of Maryland, Baltimore, MD 21201-1192 

Basic epidemiological documentation as well as non human primate experimentation 

prompted us to develop anti Tat therapeutic vaccine based on Tat toxoid, a protein non 

toxic but immunogenic HIV-1 Tat derivative. Phase I trial conducted at the Hemophiliac 

Bonomi Center of Milan (Pr. Gringeri) in 1997-1998 and Phase I/II trial organized by 

Aventis Pasteur both at Hospital St-Pierre (Pr. Clumeck, Bruxelles) and at the IHV 

(Pr. R. Redfield, Baltimore) in 2001-2002 showed that the Tat toxoid immunogen 

adjuvanted with either Seppic oil (ISA51), DcChol or Alum was safe and immunogenic. 

A structured treatment interruption study (STI) monitored according to EU guidelines was 

conducted at Brussels (Pr. Clumeck) on the 31 vaccinees who received either a DcChol 

adjuvanted Tat Toxoid (n=12), a DcChol placebo (n=8) or non adjuvanted Tat Toxoid 

(n=11). This 2 year study showed that vaccines developing high titer of antibodies 

inhibiting Tat activity prolonged HAART-interruption. 


PL 1 

Bird Flu and Human Risk 

Alice Croisier, WHO (Geneva, Switzerland) 

Avian influenza A (H5N1) virus circulation in avian populations is posing a threat to human 

health. Beyond the virus's ability to cause human infection and illness, the greater threat 

for humanity relates to the risk for the virus to become more adapted to humans or to 

re-assort with another influenza A virus sub-type. Should this happen it could result in a 

new influenza pandemic. H5N1 is not the only influenza virus sub-type currently posing a 

threat for a new emergent pandemic strain, but, it is the most visible and likely at this time. 

It's geographical spread and range of species affected is unprecedented offering 

countless opportunities for virus modification. 

The pathogenicity of a new pandemic influenza A virus can not be predicted, nor can the 

timing of the pandemic, the speed of its spread or the populations which will be at most 

risk of serious illnesses or death. 

The health impact of a pandemic could range from relatively mild to severe. We can not 

ignore the possibility of another pandemic like that in 1918 with an estimated global 

human mortality of approximately 40-50 million. Regardless of ultimate severity, a 

pandemic vaccine probably will not be available in sufficient quantity in the early stages of 

a pandemic and antiviral drugs will be limited in supply. Mitigation of morbidity and 

mortality during the first wave of the next influenza pandemic therefore will substantially 

depend upon the effectiveness of non-pharmaceutical public health interventions. 

Pandemic preparedness begins with resource planning to facilitate optimal care for 

patients, case management, communication to the general public and preparations to limit 

hospital and community-based transmission. Recommendations may also be made to 

mitigate the socio-economical impact of the pandemic. 

There is much to learn about the determinants of spread of a pandemic and on specific 

interventions which are likely to mitigate it's impact. Further studies would help prepare for 

future pandemics. 

Highly pathogenic avian influenza A(H5N1) and other future pandemic threats will not go 

away but effective preparations can make a significant difference. 



PL 2 

HIV & AIDS Research: The Light and the Dark - Then and Now 

Robert C. Gallo, MD 

Director 

Institute of Human Virology and Professor, Departments of Microbiology and Immunology 

and Medicine, University of Maryland Baltimore, Baltimore, Maryland 

It began in the middle of 1981, or at least that is what most people think because that is 

when medical science first recognized the new disease soon to be denoted as the 

Acquired Immune Deficiency Syndrome (AIDS). It was the best of times. It was the worst 

of times. Worst of times - because by the late 1970s a consensus emerged in the 

medical-scientific community that epidemics were over, that viruses were not causes of 

any human cancers, and that retroviruses of humans did not exist. Best of times - 

because just before AIDS was first recognized the technology to grow human T-cells with 

Il-2 and very sensitive assays for retroviruses had been developed. Both technologies 

would be critical to the discoveries of human retroviruses. Soon enough the above 

mentioned biases were shattered when in the early 1980s human retroviruses were 

discovered, some of them (HTLV-1) shown to cause unusual forms of leukemia, other 

viruses shown to cause about 15% of all human cancer, and another retrovirus (HIV) 

shown to cause one of the most serious epidemics in history. 

Thus, it is now over 25 years since the first discovery of human retroviruses (HTLVs, 

1980), just 25 years since the first description of AIDS (1981), and over 20 years since the 

first isolate of HIV (1983), and the demonstration that HIV was the cause of AIDS (1984). 

During this period enormous progress was made in basic studies of human retroviruses, 

including the elucidation of their replication cycles and much of their pathogenic 

mechanisms. 

Both HTLV and HIV have multiple redundant mechanisms for their survival. For HTLV, it 

is in the several mechanisms which promote growth of provirus containing cells. This 

appears to be necessary because HTLVs replicate inefficiently. In contrast, HIV has 

evolved multiple redundant mechanisms for maintaining virion numbers and survival. It is 

by these redundant mechanisms evolved for their survival that disease occurs: the 

occasional T-cell leukemia of HTLV and the common immune deficiency by HIV (see Gallo 

R. Human Retroviruses after 20 years: Perspective from the past and Prospects for their 

future control. Immunol Rev 185; 236-262, 2002). 

Probably we now know as much about HIV as we do about any virus. Similarly, we may 

know as much or more about AIDS than we do about any disease. However, at the onset 

of the AIDS epidemic HIV presented unique challenges. Unlike past viral epidemics or the 

recent SARS epidemic AIDS became manifest only after some 5-15 years from the time 

of infection. Moreover, by the time clinical AIDS developed, the patient had multiple 

microbial infections. These two features combined to make the demonstration of the HIV 

cause of AIDS a formidable challenge. Essential to success was the development of a 

sensitive, specific, and simple blood test which provided overwhelming evidence that HIV 

was the cause of AIDS. The blood test was also quickly adopted to screening the supply 

of blood for preventing HIV blood transmission, and soon (by early 1985) made the blood 

supply safe for most industrial nations. This became the field's first practical advance. 

A second practical advance also began in the mid-1980s with the first anti-HIV therapy 

(AZT) and culminated in the mid-1990s with combination of inhibitors of HIV enzymes (RT 

and protease) in a 3 to 4 drug cocktail, which provided a dramatic clinical achievement and 

for the first time in medicine enforced the notion that persisting viruses can be chemically 

attacked. 


Thus, for some, HIV no longer produces a predictable death. Rather, with therapy HIV is 

often a chronic disease with far less morbidity. Furthermore, pediatric AIDS in the 

industrial world is almost over. However, the good news is quickly tempered by: (1) the 

emergence of HIV drug resistant mutants; (2) the toxicity of drugs when used and needed 

for years and probably for life-time; (3) the rise in cancer incidence in infected persons; (4) 

the increasing epidemic in some populations in Western nations; (5) the increasing 

numbers of doubly infected people with TB or HCV and HIV, and their worse prognosis; 

(6) the still considerable uncertainty of the future of the epidemic; (7) the lack of 

preventive vaccine; and (8) lastly, and most important, the dramatic epidemic in parts of 

the world that provide an enormous financial and infrastructure challenge. 

I will use this presentation to: (1) to discuss some of the lessons from the early period 

(before and just after AIDS, and subsequently HIV, were recognized); (2) summarize some 

of HIV's pathogenic mechanisms; (3) describe the drug therapy programs of the Institute 

of Human Virology with developing nations; and (4) outline a path to a preventive 

vaccine. 


SS 1.1 

The importance of HIV drug resistance testing in daily practice 

Vincent Soriano 

Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain 

Background 

Optimal care of antiretroviral therapy in HIV-infected individuals requires the integration of 

CD4 counts, plasma HIV-RNA and drug resistance testing. Recent guidelines 

recommends resistance testing before initiation of antiretroviral therapy, since 10-15% of 

drug-naïve individuals may harbour drug resistance as consequence of transmission of 

resistant viruses. Drug resistance testing is also required to optimize rescue interventions 

in patients experiencing virological failure under any treatment regimen. 


The resistance database of Hospital Carlos III records clinical information along with 

resistance mutations in samples submitted from different hospitals across Spain since 

year 1996. Several studies of prevalence, trends over time and clinical correlates of 

resistance mutations have been performed over the last decade in HIV-1 seroconverters, 

chronically drug-naïve individuals, persons infected with non-B subtypes and treatmentexperienced 

patients. 

Results 

Nearly 4,000 genotypes have been recorded until mid 2006, of whom 350 belongs to 

HIV-1 seroconverters, 300 to chronically drug-naïve individuals and the remaining vast 

majority to antiretroviral-experienced patients. Real and/or virtual phenotypes are 

available for a substantial number of samples. Clinical correlates (viral load and CD4 

counts) following antiretrovirals used after genotyping are available for nearly 2000 

patients. Among the main findings are the original recognition of the antagonism between 

rtK65R and TAMs, the role of proI47A in causing lopinavir resistance, and the differential 

transmission of drug resistance mutations. 

Conclusions. Drug resistance will continuous to challenge HIV therapy. A better 

knowledge of the mechanisms of resistance by clinicians and how to optimally use 

resistance information will translate in a better HIV management. Both phenotypic and 

clinical correlates of drug resistance mutations will help to interpret more appropriately 

resistance mutations for the older and new coming antiretrovirals. 


SS 1.2 

Case session: Virco Type HIV-1 and its use predicting susceptibility to 

antiretroviral drugs in HIV-infected patients with multiresistant HIV-1 

Jürgen K. Rockstroh, Medical Department I, Bonn University, Germany 

Since the discovery of HIV as the cause for acquired immunodeficiency syndrome in 1982 

more than 40 Mio. people have been infected with HIV worldwide. In industrialized 

countries antiretroviral therapy specifically inhibiting virus replication has become 

available since 1984. Even though with the introduction of highly active antiretroviral 

therapy in 1996 long-term durable suppression of HIV-RNA below the level of detection 

and consecutive significant prolongation of patient's life became available, the long-term 

efficacy of this treatment concept has been hampered by the emergence of drug resistant 

viruses. Presently, it is estimated that between 10 and 20 % of antiretroviral naive patients 

have acquired a primary resistant HI-virus, limiting the choice of available antiretroviral 

agents with full antiviral activity. 

Patients failing highly antiretroviral therapy due to acquired drug resistances have 

markedly reduced chances of achieving again durable suppression under a new 

antiretroviral regimen. It has convincingly been shown that using genotypic resistance 

assays for the detection of aminoacid mutations within the RNA of HIV can reliably predict 

resistance to specific antiretroviral agents with the help of interpretation systems. It is 

therefore present standard of care to offer patients who are failing their current 

antiretroviral therapy a genotypic resistance assay. With the help of a genotypic 

resistance testing, still active antiretroviral drugs can be identified among drugs with 

partial or full resistance and the potency of a new antiretroviral regimen can be maximized. 

Presently there are numerous interpretation systems on the market allowing the 

assessment of activity or potential activity of individual antiretroviral agents given a 

genotypic analysis of the sample virus. Due to a lack of comparison of interpretation 

systems, no gold standard on how to interpret a genotypic report is available. As different 

interpretation systems may lead to substantial differences in the assessment of activity of 

an individual drug, treatment decisions based upon interpretation systems may be of 

major clinical impact for a particular patient. Therefore clinical studies trying to assess the 

efficacy of genotypic interpretation systems are desperately needed. 

VircoTYPE HIV-1 is an HIV-1 genotype analysis report that combines genotype, 

phenotype and additional clinical information in order to facilitate the choice of a new 

antiretroviral therapy and possibly maximize the efficacy of this regimen. The vircoTYPE 

HIV-1 provides a quantitative, data driven assessment of resistance to HIV-1 antiretroviral 

drugs, based on a large database of clinical viral genotypes and corresponding drug 

phenotypes, expressed in fold changes (IC50 specific sample compared to IC50 wildtype 

virus). The vircoTYPE HIV1-1 Foldchange results are then related and interpreted making 

use of Cut-Offs, either Biological Cut-offs derived from fold changes distribution of clinical 

isolates of drug naïve patients or (and most important) Clinical Cut-Offs based on the 

clinical observations (virological outcome) collected from various clinical trials and patient 

cohorts in vivo. 

In this session clinical case scenarios will be discussed highlighting the difficulty of 

correctly assessing antiretroviral resistance and predicting antiviral efficacy of a new 

regimen. 


SS 1.3 

Virtual phenotype and Clinical Cut-offs: the next generation of resistance testing 

Jorge Villacian, Mechelen - Belgium 

Introduction 

Antiretroviral (ARV) drug resistance testing is a key component of HIV-1 disease 

management and is aimed at assisting clinicians and virologists in optimizing the 

selection of ARV regimens for individual patients. 

Genotypic resistance tests are qualitative in nature and identify mutations in the viral 

genome that affect ARV drug susceptibility, whereas phenotypic tests are quantitative and 

determine the level of resistance of the HIV-1 virus to ARV drugs, expressed as Fold 

Change in IC50 (FC). 

Virco ® TYPE HIV-1 combines genotypic information with a predicted Phenotype and 

Clinical Cut-Off (CCO) values to give optimal guidance to clinical decision-making. The 

Phenotype is predicted from the Genotype using an extensive database of previously 

determined Genotypes and Phenotypes from clinical isolates, and a bio-informatics based 

methodology VirtualPhenotype TM (VPT). 

VirtualPhenotype TM - LM is a new version of VPT that uses Linear Regression Modeling 

and Virco's Genotype/Phenotype correlative database. This new approach identifies 

resistance-associated mutations, calculates their weighted contribution to resistance, and 

makes phenotypic predictions. 

VirtualPhenotypeTM- LM 

Applied to HIV-1 drug resistance analysis, VirtualPhenotypeTM- LM uses a set of multiple 

linear regression models (one for each drug) capable of predicting a sample's Phenotype 

(the outcome variable Y, FC) from the contribution of individual mutations (independent 

variables X) in its Genotype. The LMs are derived from a database that contains the 

Genotypes (all mutations) and Phenotypes (measured FC according to AVG) from 6,143 

- 41,958 clinical isolates. By modeling the relationship between the Genotype and the 

Phenotype, each mutation and combination of two mutations that has a significant effect 

on drug susceptibility is identified and assigned a Resistance Weight Factor (RWF) 

according to its contribution to the FC. VPT-LM analyzes not only individual mutations but 

also pairs of mutations, thus taking into account the effect that synergistic or antagonistic 

interactions between mutations may have on phenotypic resistance. The FC of an 

unknown sample is predicted by adding up the contributions or RWFs of the individual 

mutations and mutation pairs that were identified in the patient's virus Genotype. 

Clinical Cut-offs 

CCOs are computed using a sophisticated statistical model in order to provide guidance 

as to the likelihood of response to ARVs in vivo. Virco's CCOs are applicable to diverse 

populations, and all drugs were studied with consistent statistical methods. The viral 

strains used to set the CCOs came from a diverse population of patients, with a mix of 

treatment-naïve and treatment experienced individuals. 

CCOs have an advantage over BCOs, especially in the protease inhibitor resistance 

predictions because BCOs do not account for ritonavir boosting. 

There are two breakpoints derived for the majority of drugs, the FC value associated with 

20 percent loss of the WT reference response is the CCO1 (low), while the FC associated 

with 80 percent loss of the WT reference response is established as the CCO2 (high). 


SS 1.4 

HIV Resistance Testing in Clinical Practice: Comparative Analysis between 

Genotypes and Virtual Phenotypes 

L.Bocket-Mouton 1 , M.Lazrek 1 , H.Melliez 2 , C.Roussel 3 , F.Ajana 2 , D.Hober 1 , Y.Mouton 2 , 

Y.Yazdanpanah 2 . 

1 

Virology Department, Centre Hospitalier Universitaire de Lille, France 

2 

Infectious Diseases Department, Centre Hospitalier de Tourcoing, France 

3 

Virology Department, Centre Hospitalier Universitaire d'Amiens, France 

Background 

Drug resistance testing has become standard of care to guide antiretroviral treatment in 

HIV-infected patients failing therapy. Several assays have been standardized to assess 

HIV drug susceptibility: genotypes, phenotype or virtual phenotypes. The objective of this 

study was to compare genotype resistance testing and vircotype ® HIV1 interpretation of 

resistance in patients failing HAART. 

Methods 

66 heavily pre-treated HIV-infected patients experiencing virological failure were enrolled 

in this study. In each patient, a genotype resistance testing using the ANRS 

algorithm was performed based on the result of which a subsequent antiretroviral regimen 

was initiated. Viral load decrease was determined 12 weeks after treatment initiation. 

Virtual phenotype resistance tests were retrospectively performed in all patients. First we 

compared genotype and virtual phenotype resistance mutations profiles. Results were 

considered concordant or discordant (minor discordance=susceptible vs. intermediate or 

intermediate vs. resistant; major discordance=susceptible vs. resistant). Next we looked 

at viral load decrease at 3 months in those patients in whom drug were considered as 

susceptible by genotype and resistant by virtual phenotype resistance testing. 

Results 

NNRTI susceptibility predictions were always concordant between the two tests. In NRTI 

class, interpretation of the sequences showed concordance between the two systems in 

15 patients (23%), but minor discordances in 21 patients (32%) and major discordances 

in 30 patients (45%). In PI class, interpretation showed concordance in 20 patients (30%), 

but minor discordances in 25 patients (38%) and major discordances in 21 patients (32%). 

In 12 patients (18%) the two systems displayed major discordances in both NRTI and PI 

susceptibility predictions. In 13 out of 16 patients in whom at least one drug was 

considered susceptible by genotype resistance testing and resistant by phenotype 

resistance testing, viral load decrease was

SS 2.1 

The Lessons we have Learned over the Last Decade 


SS 2.2 

Differentiating between Different Options 


SS 2.3 

The Future of Therapy 


SS 3.1 

Brain and HIV 

Jacques Gasnault, Kremlin-Bicêtre - France 

A greater number of patients over 50 years of age are now living with HIV in industrialized 

countries. This epidemiologic trend will continue to increase as a result of both prolonged 

survival due to effective antiretroviral treatment and the growing proportion of delayed 

diagnoses of older individuals with occult HIV disease. Despite a better virological 

response to combination antiretroviral therapy (cART), older patients are at a higher risk 

of HIV disease progression than youngers, for at least two reasons: first, they tend to be 

diagnosed at a more advanced stage; second, they have a delayed immune response to 

cART. There is emerging evidence that older HIV-infected individuals may be at greater 

risk for cognitive disorders. Some studies have identified a higher frequency of 

neurocognitive dysfunction in older than in younger HIV-infected persons. This impairment 

may vary in severity from a dementing illness (HIV-associated dementia) to a mild clinical 

change (minor cognitive motor disorders). Because of the overlap in cognitive functions 

that are affected by aging as well as by HIV-1 infection, one might expect that aging may 

potentiate the effects of HIV-1 on cognition in older individuals. In HIV-infected individuals 

as in general population, older age has been found to be associated with higher risk of 

complications as cardiovascular disease or diabetes, which can lead to a cognitive 

decline. The observation that HIV, advanced age, and concomitant neurodegenerative 

disorders as Alzheimer disease may interact in additive or synergistic ways raises many 

questions regarding best practice among this population. 

SS 3.2 

Long-Term Cardiovascular Troubles of HIV Patients 


SS 3.3 

Cancer and HIV 



SS 4.1 

Pharmacologic Prerequisites 


SS 4.2 

Resistance at Stake 


SS 4.3 

From Lipids to Cardiovascular Risk 


SS 4.4 

Future Trends 


SS 5.1 

HIV-associated lipodystrophy: pathophysiology 

Jacqueline Capeau 

Inserm U680 Faculté de Médecine Pierre et Marie Curie, 27 rue Chaligny 75012 Paris, 

France 

Hôpital Tenon, AP-HP, Paris 

The lipodystrophy syndrome associates altered body fat repartition (peripheral lipoatrophy 

and/or visceral fat hypertrophy) and metabolic alterations (dyslipidemia, insulin resistance 

and altered glucose tolerance). The pathophysiology of these alterations is complex: in 

addition to factors linked to the patient and to HIV infection, different studies argue for 

adipose tissue being the target of some protease inhibitors (PIs) and of thymidine 

analogues among the nucleoside analogues inhibitors of the viral reverse transcriptase 

(NRTIs) acting through different mechanisms. Thymidine analogues are able to induce 

mitochondrial dysfunction and to modify adipocyte phenotype, these alterations being 

reverted in vitro by the addition of uridine. They also modify the adipose tissue pattern of 

secretion of cytokines (TNF , IL-6) and other adipokines (adiponectin, leptin) probably 

through the production of reactive oxygen species. Some PIs also act on adipocytes, alter 

their differentiation and insulin sensitivity and also the pattern of secretion of adipokines 

by adipose tissue. Lipodystrophic adipose tissue is markedly modified, with decreased 

adipocyte and increased macrophage number resulting in a state of low grade 

inflammation. These hypotheses could explain the loss of adipose tissue, while the 

mechanisms of visceral fat hypertrophy remains speculative. Since some adipokines and 

the free fatty acids released by insulin resistant adipocytes play a major role in the control 

of liver and muscles insulin sensitivity, these alterations are probably involved in the 

metabolic alterations seen in the patients with increased risks of cardiovascular disease 

and of steatohepatitis. Besides strategies using plastic surgery, the treatment of 

lipodystrophy remains difficult and, at present, privileges the switch of the more 

deleterious drugs towards new molecules less aggressive for adipose tissue. Clinical trials 

using uridine to reverse thymidine analogues toxicity or the thiazolidinedione pioglitazone 

showed promising results on peripheral lipoatrophy but require further validation. 


SS 5.2 

HIV-associated facial lipoatrophy and therapeutic approaches : therapeutic 

strategies to treatment of HIV-Facial Lipoatrophies 

Christophe Compagnon, Marseille - FRANCE 

Lipoatrophy prevalence: Many cross studies outline lipodystrophy prevalence from 18 to 

80%. In the "Aproco" cohort, 62% of the patients treated in first intention with HAART 

including an IP show at least one lipodystrophy sign and 25% show facial atrophy. 

Nevertheless, number of lipodystrophies seems to decline thanks to new HAART. 

Therapeutic alternatives: There are 3 main treatments for lipodystrophy: medical means 

by less toxical HAART, addition of adjuvant treatments like uridine and pioglitazone, those 

being at an experimental stage. On a surgical basis, there are two therapeutic approaches 

for facial lipoatrophy: autologuous fat tissue transplantation with Coleman technique 

(lipo-filling) and fillers. Main adverse effects of the Coleman technique are: "hamster" 

syndrome 16%, re-operation 37%, facial oedema 50% [Guaraldi G et al.], more rarely, fat 

accumulation may need a re-modeling by liposuction. Biodegradable fillers: 1. Collagen: 

Allergic risk is one of the most important side effects. A test must be done prior to 

injection, particularly for bovine collagen. FDA has approved human collagen, less 

allergenic, in March 2003. Effects of this kind of treatment remain 3 to 6 months. 

2. Hyaluronic acids: Different kinds of hyaluronic acids exist depending on their viscosity, 

they are easy to use. Although effects are immediate, they remain only few months (3 to 

9). 3. New-Fill (L-polylactic acid): This biodegradable injectable medical device is the most 

used in treatment of facial lipoatrophy in HIV-infected patients. It is the only product 

reimbursed by social security (France) in this indication and FDA has approved it in 2004 

in this indication too. Restoration of volume in depressed areas of the face by stimulating 

neocollagenesis is progressive and effects remain about 2 years. 4. Eutrophill ® (Outline) 

is a polyacrylamide hydrogel obtained by polymerization of acrylamide monomers with an 

official half-life of 5 years. Under evaluation. There are also non biodegradable implants 

like Bio-Alcamid ® (polymeric material composed of alkylimide-amide groups) Bio-Alcamid 

can be defined a sort of "endoprosthetis". Adverse events: Most of the adverse events 

encountered with fillers are depending on their re-absorption lasting and their mechanism 

of action. Short re-absorption products are of short lasting effect. Longer lasting products 

may occasion micronodules, induration areas, reactive fibrosis and granulomas. 

Infections and casts may occur with non-biodegradable product. Adverse events are more 

often subject to re-absorption lasting of the product. Therapeutic strategy: Patients should 

be informed of benefits and drawbacks of each technique. The selection of the technique 

and the product will be related to the lipodystrophy grade (moderate, intermediate, 

severe). Autologous graft (Coleman technique) will be proposed to patients with areas 

amenable to liposuction, in that case, a temporary social exclusion should be necessary 

Moderate lipoatrophy 

Therapeutic adjustment 

Long lasting or short lasting biodegradable product 

Pioglitazone (research in progress) 

Moderate lipoatrophy 


Autologous grafs when possible 

Long lasting biodegradable product in first intention or non-biodegradable implant 

Severe lipoatrophy 


Long lasting biodegradable product in first intention or non-biodegradable implant 

Clinical Cases: examples of facial lipoatrophy treatment will be shown. 


SS 5.3 

HIV-associated facial lipoatrophy and therapeutic approaches : Pratical 

Management : The L-Polylactic Acid Case 

Marc Dolivo - PARIS FRANCE 

New-FillTM (L-polylactic acid) is a synthetic polymer, biocompatible, biodegradable and 

immunologically inert. New-FillTM has to be injected deeply into the dermis or into the 

subcutaneous tissue. New-FillTM obtained reimbursement in France in facial lipoatrophy 

of HIV infected patients after HAART treatment. One of the conditions of this 

reimbursement is the follow-up treatment safety's monitoring as well as treatment 

modality follow-up for every patients with the assistance of a mandatory notebook. Title of 

the study: Monitoring of cohort of patients HIV-associated facial lipoatrophy due to HAART 

treated with New-FillTM for correction of facial lipoatrophy. Objectives: Primary objective 

is to describe New-FillTM' safety in observational conditions. Secondary objective is to 

describe modalities of use of the product in order to compare them to French Agency 

recommendation. Method: Study plan consist in 3 years observational, longitudinal and 

descriptive follow-up. Datas were collected with mandatory notebooks filled-in by 

investigators initiating treatment with New-FillTM. Note books were requested by French 

authorities and implemented for every New-FillTM'injector. Notebooks were completed at 

every injection visit (from 1 to 5), and at the last visit 2 month after last injection. Results: 

Here are results of intermediate analysis of 52 centers in 15 regions of France uniting 261 

patients'inclusion. Description of investigator population: 66% are dermatologists and 29% 

are plastic surgeons. The median duration from New-FillTM injection technique training is 

1 year [0.00 - 11.00], 48.8 % less then 1 year , 19.5 % between 1 and 3 years and 31.7 

more then 3 years. Study population: median age 45.3 years [27.63 - 74.64], 89.5 of male 

patients. Median period of HIV infection is 15 years [1.00 - 25.00], the median duration of 

HAART treatment is 10 years [1.00 - 22.00]. Median rate of CD4 count is 450 cells/mm3 

[3.00 - 1270] with median viral load of 50 copies/ml [0.00 - 98200.00]. 68 % of the patients 

outlined a viral load lower then 400 copies/ml. The median duration of facial lipoatrophy 

diagnostic is 5 years[0.00 - 20.00]. 39.2% of patients had already received New-FillTM 

injections before. New-FillTM treatment: 48% of patients received 5 injections, 12.1 4 

injections, 15.7% 3 injections and 11.7 % 2 injection, 12.5 % received only one injection. 

Result: subjective evaluation of efficacy of the treatment: investigators assessed 

improvement of facial lipoatrophy in 95.6 of patients. At the last consultation 2 month after 

the last injection, subjective evaluation of the efficacy of New-FillTM were realised by the 

investigator. Investigator were very satisfied in 50.8% of cases, satisfied in 46.2% of 

cases, poorly satisfied in 2.5% of the cases and disappointed for one patient (0.5% of 

cases). Subjective evaluation of treatment's efficacy was also realised by patients. 107 

were very satisfied(53.5%), 84 satisfied(42%), poorly satisfied 7 patients(3.5%) and 

disappointed by 2 patient (1%). Safety data: Side effects subject to be related to injections 

were collected at every injection consultations with check list ready to use, empty spaces 

to fill-in and with "New-FillTM potential adverse incident reporting Form". We cocellected 

mainly side effect directly related to injection technique 12.5% of pain (n:31), 8.5% bruises 

(n:21), 7.7% bleeding (n:19), 4% rednesses at injection points(n:10) and 4% 

oedemas(n:10). Nodules and/or indurations areas were reported in 6% of patients and 

granuloma in 1.6% (n:4). Treatment discontinuation: 3 patients interrupted injections 

because of nodule and/or in durations areas and 2 patients owing to granulomas. 82 

patients precociously interrupted injections being satisfied before the term of protocol. 

Conclusion: These first results show a high level of satisfaction from patients and 

investigators. Half of patients needed less than 5 injections of New-FillTM. On the safety 

point of view, most of side effects are benign and temporary with few nodules/granulomas 

which still must be monitored. Clinical Cases: examples of facial lipoatrophy treatment will 

be shown. 


SS 6.1 

How to improve the use of new antiretroviral agents? 

Anne-Marie Taburet 

Clinical Pharmacy, hospital Bicêtre, Assistance Publique Hôpitaux de Paris, France 

Although potent antiretroviral drug regimens are available, a number of factors may limit 

their efficacy and safety. Among those, drug-drug interactions, non adherence and 

adverse drug reactions need to be characterized for optimal and sustained viral 

suppression. 

Protease inhibitors (PIs) are potent antiretroviral drugs with proven efficacy in 

HIV-infected patients. However most PIs have unfavourable pharmacokinetic properties 

which were largely overcome combining a small dose of ritonavir, a potent inhibitor of 

CYP3A and possibly transporters. This has lead to the lopinavir/ritonavir fixed dose 

combination and to current recommendation for using ritonavir boosted PIs. Highly active 

antiretroviral therapy is the combination of two nucleoside analogs (NA) and either one PI 

or one non nucleoside reverse transcriptase inhibitor (NNRTI). Although interactions 

between NA were thought to be minimal, a decreased viral efficacy was demonstrated 

when didanosine and tenofovir are combined. Lower atazanavir concentrations after 

addition of tenofovir to the regimen is another unexpected interaction likely occurring at 

the gut level. 

For patients who are in virological failure after several antiretroviral regimens, combining 

two ritonavir boosted PIs may be an option. One potential problem is the risk of negative 

pharmacokinetic interaction which are difficult to predict, as some PIs have inhibiting and 

inducing properties. Several combinations have been extensively studied such as the 

amprenavir or fosamprenavir and lopinavir/ritonavir combination or tipranavir and 

lopinavir/ritonavir or saquinavir or amprenavir combinations. 

Wide between and within patient pharmacokinetic variabilities remain of concern and are 

dependant on a variety of factors such as food effect, adherence in term of compliance 

and persistance. Whether therapeutic drug monitoring is a useful tool to improve drug 

exposure remains debated. 

Knowledge of major drug-drug interactions and adherence profile may help to select the 

best antiretroviral drug regimen, hence avoiding virological failure and the occurrence of 

side events and will translate into clinical benefits. 


SS 6.2 

Is there HIV-1 evolution in cellular reservoirs during prolonged suppressive 

HAART? 

Jacques Izopet, Toulouse - France 

Reservoirs of HIV-1 are a major obstacle to virus eradication. There is therefore a need to 

clearly understand the molecular nature of the virus populations that persist in patients 

with sustained suppression of plasma viremia on highly active antiretroviral therapy 

(HAART). The genotypes of HIV-1 quasispecies isolated from highly purified blood cell 

types taken from patients with sustained undetectable viral loads on HAART for 7 years 

were analysed. Polychromatic flow cytometry was used to sort naïve and memory CD4 T 

cells, CD14 monocytes, and CD56+CD3 natural killer (NK) cells from the total peripheral 

blood mononuclear cells. Clonal analysis was used to determine coreceptor use and 

drug-resistance genotypes of HIV-1 quasispecies in the sorted blood cell types. HIV-1 

DNA was detected in memory and naïve CD4 T cells and in CD14 monocytes. 

Phylogenetic analyses demonstrated that the various blood cells types harboured 

genetically distinct HIV-1 quasispecies. Drug-resistant variants as well as CCR5 and 

CXCR4-using viruses were distributed differently from one cell type to another. 

A longitudinal analysis of the virus found in cellular reservoirs also showed a switch from 

R5 to X4 variants in proportions similar to what is observed during natural HIV-1 infection. 

Importantly, the patients harbouring predominantly X4 variants during HAART had lower 

CD4+ T-cell count on HAART than did patients harbouring R5 variants. Finally, recent data 

showed that the low CD4 cell recovery in patients with X4 variants could be linked to 

persistent T-cell activation rather than impaired thymic activity. 


SS 6.3 

Tipranavir is a Potent Protease Inhibitor with an Activity against IP-Resistant Forms 

of HIV-1 

Mark A. Wainberg 

Centre sur le SIDA de l'Université McGill, Hopital Juif de Montréal 3755 Chemin-Cote-Ste- 

Catherine Montréal, Québec, CANADA H3T 1E2 

Tipranavir (TPV) has been demonstrated in both the Resist I and Resist II studies to be 

highly effective against strains of HIV-1 that contain multiple mutations in PR associated 

with resistance to the PI family of drugs. In studies that assessed TPV vs a comparator PI, 

TPV was shown to be especially effective in patients who possessed 5 or 6 key 

mutations in PR associated with PIs. TPV, when combined with other effective drugs, was 

able to achieve suppression of viral load to non-detectable levels in over 70% of 

individuals in highly treatment-experienced populations. The data strongly suggest that 

TPV may be the only alternative among approved drugs for use in the salvage setting, 

although it is recognized that the durability of TPV in this context may be enhanced 

through inclusion of other effective agents as well in order to forestall viral replication and 

the development of additional drug-resistance associated mutations. 


Acknowledgements - Remerciements 

The Steering Committee expresses its sincere gratitude 

to the following Compagnies for their support 

of the 14 th ISHEID 

Le Comité d’Organisation exprime tous ses remerciements 

pour le support apporté par les partenaires de l’industrie du 

14 e ISHEID 

ABBOTT FRANCE 

BRISTOL-MYERS SQUIBB 

GILEAD 

VIRCO BVBA 

BOEHRINGER INGELHEIM 

ROCHE 

SANOFI-AVENTIS 

GLAXOSMITHKLINE 

JANSSEN CILAG 

BAYER HEALTHCARE DIAGNOSTICS 

BIOALLIANCE PHARMA 

CHIRON 

FUTURE SCIENCE GROUP 

IVAGEN 

PFIZER 

UCB PHARMA 

WISEPRESS ONLINE BOOKSHOP LTD 


ABBOTT FRANCE 

Abbott is a global, broad-based health care compagny devoted to the 

discovery, development, manufacture and marketing of pharmaceutical, 

nutritionals, and medical products, including devices and diagnostics. 

Some 60,000 individuals worldwide share our vision of delivering 

breakthrough products that make a significant impact on medical practices, 

on quality of care, and on the lives of the people who rely on them to be alive 

and well. 

Headquartered in Chicago, Abbott serves customers in 130 countries. 

Additional information about Abbott and virology 

Abbott has been a leader in HIV/AIDS research since the early years of the 

epidemic. In 1985, Abbott developed the first licensed test to detect HIV 

antibodies in the blood, and remains a leader in HIV diagnostics. 

Today, Abbott retroviral and hepatitis tests are used to screen more than half 

of the world's donated blood supply. To treat those with HIV, Abbott scientists 

have developed two protease inhibitors. 

Abbott est un groupe international de premier plan dans le domaine de la 

santé qui se consacre à la recherche, au développement, à la fabrication et 

à la commercialisation de médicaments, de produits de nutrition médicale 

ainsi que des instruments et dispositifs de diagnostic. 

Environ 60 000 personnes dans le monde travaillent à mettre à la disposition 

des patients des produits d'avant-garde qui influent grandement sur la 

pratique médicale et la qualité des soins. Son siège social est situé dans la 

banlieue nord de Chicago, Abbott commercialise ses produits dans plus de 

130 pays. 

Informations supplémentaires à propos d'Abbott et de son engagement dans 

le domaine de la virologie. 

Abbott est un des leaders dans le domaine de la recherche VIH/SIDA depuis 

les premières années de l'épidémie. En 1985, Abbott lance le premier test de 

dépistage des anticorps du VIH dans le sang, et elle demeure aujourd'hui un 

référent dans le diagnostic du VIH. Les tests virologiques Abbott sont utilisés 

pour tester plus de la moitié du sang utilisé en transfusion dans le monde. 

Par ailleurs, afin de traiter les patients séropositifs, les scientifiques d'Abbott 

ont développé deux inhibiteurs de protéase. 

Abbott France 

10, rue d'Arcueil - BP 90233 - 94528 Rungis Cedex 

Tél. : +33 (0)1 45 60 25 00 - Fax : +33 (0)1 45 60 04 98 

www.abbott.fr 


BIOALLIANCE PHARMA 

BioAlliance Pharma 

59, Boulevard du Général Martial Valin 

75015 PARIS - France 

Tel : +33 (0)1 45 58 76 00 

Fax : +33 (0)1 45 58 08 81 

E-mail : bioalliance@bioalliancepharma.com 

www.bioalliancepharma.com 


BOEHRINGER INGELHEIM 

The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical 

companies. Headquartered in Ingelheim, Germany, it operates globally with 

143 affiliates in 47 countries and almost 37,500 employees. Since it was 

founded in 1885, the family-owned company has been committed to 

researching, developing, manufacturing and marketing novel products of 

high therapeutic value for human and veterinary medicine. 

In 2005, Boehringer Ingelheim posted net sales of 9.5 billion euro while 

spending almost one fifth of net sales in its largest business segment 

Prescription Medicines on research and development. 

For more information please visit www.boehringer-ingelheim.fr 

Le groupe pharmaceutique Boehringer Ingelheim, dont le siège se situe à 

Ingelheim en Allemagne, figure parmi les 20 premières entreprises du 

médicament au monde. Le groupe compte 143 filiales dans 47 pays et près 

de 37 500 employés. Cette entreprise indépendante à capitaux privés est 

engagée depuis 1885 dans la recherche et le développement, la fabrication 

et la commercialisation de produits d'intérêt thérapeutique majeur à usage 

humain et vétérinaire. 

En 2005, Boehringer Ingelheim a enregistré un chiffre d'affaires de 9,5 

milliards d'euros et a consacré à la recherche et au développement, près de 

20 % du chiffre d'affaires des produits de prescription. 

Si vous souhaitez en savoir davantage sur Boehringer Ingelheim, n'hésitez 

pas consulter notre site Internet à l'adresse suivante : 

www.boehringer-ingelheim.fr 

Boehringer Ingelheim France 

12, rue André Huet 

51100 Reims 

Tél. : +33 (0)3 26 50 45 45 

Fax : +33 (0)3 26 50 45 00 

www.boehringer-ingelheim.fr 


GLAXOSMITHKLINE 

GlaxoSmithKline's commitment to hospitals is primarily a story built around numerous therapeutic 

innovations. 

GSK has been present for many years in vital areas such as HIV, antibiotherapy, oncology, 

anaesthesia and, more recently, thrombosis and cardiology. In each of these areas, GSK plays 

a key role in the development of therapeutic strategies. 

With the HIV infection, for example, which is no longer an emergency pathology but a chronic 

pathology, it is now essential to consider new requirements and support the health care teams 

in order to combine for each patient the best therapeutic strategy and optimised quality of life. 

A multidisciplinary player at the service of the hospital 

GSK's commitment at the heart of the hospital provides the multidisciplinary know-how which will 

meet the requirements of the hospital players, whether scientific, economic, commercial or logistics. 

GSK's prime concerns are to offer patients novel molecules, improve the formulations and the 

therapeutic diagrams and optimise medico-economic approaches. Every patient therefore 

benefits from better use of the therapeutic breakthroughs made in the context of environmental 

changes in financing and governance. 

GSK also provides medical staff with the information they need to keep up to date with 

scientific changes and supports corporate philanthropy actions designed to improve the quality 

of life of hospitalised children. 

GSK, a long-term and qualitative partner of the hospital sector, finds solutions for the hospital's 

new requirements and new constraints. 

L'engagement de GlaxoSmithKline à l'hôpital est d'abord une histoire construite autour d'un 

grand nombre d'innovations thérapeutiques. 

GSK est présent de longue date dans les domaines essentiels comme le VIH, l'antibiothérapie, 

l'oncologie, l'anesthésie, et plus récemment la thrombose et la cardiologie. Dans chacun de ces 

domaines, GSK est un acteur à part entière de l'évolution des stratégies thérapeutiques. 

A titre d'exemple, pour l'infection à VIH qui n'est plus une pathologie d'urgence mais une 

pathologie chronique, il est aujourd'hui indispensable de prendre en compte de nouveaux 

besoins, d'accompagner les équipes soignantes afin de concilier pour chaque patient la meilleure 

stratégie thérapeutique et une qualité de vie optimisée. 

Un acteur multidisciplinaire à l'écoute de l'hôpital 

L'engagement de GSK au cœur de l'hôpital apporte un savoir-faire multidisciplinaire susceptible 

de répondre aux besoins des acteurs hospitaliers, que ce soit en matière scientifique, 

économique, commerciale ou logistique. 

Mettre à la disposition des patients de nouvelles molécules, améliorer les galéniques et les 

schémas thérapeutiques et optimiser les approches médico-économiques sont au cœur des 

préoccupations de GSK. Chaque patient bénéficie ainsi de meilleur usage du progrès 

thérapeutique dans le cadre des évolutions de l'environnement en matière de financement et de 

gouvernance. 

GSK met également à la disposition des personnels soignants les moyens d'informations 

nécessaires pour être au cœur de l'évolution scientifique et soutient des actions de mécénat 

destinées à améliorer la qualité de vie des enfants hospitalisés. 

GSK partenaire durable et qualitatif du secteur hospitalier, accompagne les nouveaux besoins 

et les nouvelles contraintes de l'hôpital. 

Laboratoire GlaxoSmithKline 

100, Route de Versailles 

78163 Marly-Le-roi Cedex 

Tél. : +33 (0)1 39 17 80 00 

Fax : +33 (0)1 39 17 17 58 

www.gsk.fr 


IVAGEN 

IVAGEN SA, a biotechnology company that through its ever increasing offer 

in both immunology and molecular biology, has been able to establish and 

equip local laboratories with state-of-the-art technologies and products. 

Thanks to its proprietary intellectual property portfolio, IVAGEN has been 

able to rapidly implement innovative technological solutions such as ANTI 

R7V ELISA & STAPH ArrayTube. 

IVAGEN S.A. est une société de biotechnologie, spécialisée dans le 

diagnostic humain, vétérinaire et végétal. Grâce à une équipe dynamique et 

un important réseau international de partenaires, nous concevons, 

fabriquons et commercialisons des réactifs pour les laboratoires de 

diagnostic. 

Le test ELISA Anti-R7V et le STAPH ArrayTube sont nos plus récents 

développement. 

Ivagen S.A. 

Zone Industrielle La Rousse 

62, route Nationale 113 

30620 BERNIS 

Tél. : +33 (0)4 66 73 17 40 

Fax : +33 (0)4 66 87 08 31 

www.ivagen.com 


TIBOTEC division de JANSSEN CILAG 

Tibotec Pharmaceuticals Ltd, filiale du groupe Johnson & Johnson est une société 

internationale de recherche et de développement pharmaceutique dont les axes de 

recherche concernent le développement de médicaments innovants dans le 

traitement du VIH/SIDA et de médicaments anti-infectieux pour des pathologies 

pour lesquelles il existe une attente médicale importante. 

Tibotec une division de Janssen-Cilag a pour vocation de mettre à disposition des 

patients des molécules issues de la recherche de Tibotec Pharmaceuticals Ltd. 

3 antirétroviraux sont actuellement en cours de développement ainsi qu'un 

antituberculeux. Tibotec une division de Janssen-Cilag développe aussi des 

programmes de recherche actifs dans le VIH, l'hépatite C et d'autres maladies 

infectieuses mortelles. 

Tibotec une division de Janssen-Cilag a pour objectif de devenir une référence 

dans le domaine de la recherche et du développement de médicaments 

anti-VIH/SIDA et anti-infectieux innovants dans des maladies non traitées. 

Tibotec Pharmaceuticals Ltd, Johnson & Johnson subsidiary, is an international 

pharmaceutical research and development company dedicated to the discovery 

and development of innovative new drugs for HIV/AIDS and other infectious 

diseases of high unmet medical needs 

Recognized as one of the companies at the forefront of HIV research, Tibotec a 

division of Janssen Cilag has 3 antiretroviral compounds in clinical development. 

The company also has an anti-TB compound in early development and several 

active discovery programs in HIV, HCV and other life-threatening infectious 

diseases. 

Tibotec a division of Janssen Cilag is committed to improving medical care and 

quality of life for patients and to developing innovative medicine and diagnostic tools 

to address unmet medical needs in infectious diseases. 

Its mission is to be world leader in the discovery and development of unique and 

innovative HIV/AIDS drugs and anti-infectives for diseases of high unmet medical 

need. 

Tibotec division de Janssen Cilag 

1, rue Camille Desmoulins 

TSA 91003 

92787 Issy-Les-Moulineaux Cédex 9 

Tél. : +33 (0)1 55 00 45 00 - 0 800 25 50 75 (N° vert) 

Fax : +33 (0)1 55 00 28 85 

www.janssen-cilag.fr 


ROCHE 

Headquartered in Basel, Switzerland, Roche is one of the world's leading 

research-focused healthcare groups in the fields of pharmaceuticals and 

diagnostics. As a supplier of innovative products and services for the early 

detection, prevention, diagnosis and treatment of disease, the Group 

contributes on a broad range of fronts to improving people's health and 

quality of life. Roche is a world leader in diagnostics, the leading supplier of 

medicines for cancer and transplantation and a market leader in virology. 

In 2005 sales by the Pharmaceuticals Division totalled 27.3 billion Swiss 

francs, and the Diagnostics Division posted sales of 8.2 billion Swiss francs. 

Roche employs roughly 70,000 people in 150 countries and has R&D 

agreements and strategic alliances with numerous partners, including 

majority ownership interests in Genentech and Chugai. Additional information 

about the Roche Group is available on the Internet (www.roche.com). 

Roche, entreprise de santé dont le siège est à Bâle, Suisse, figure parmi les 

leaders mondiaux dans les secteurs pharmaceutique et diagnostique. Ses 

produits et services novateurs trouvent leur application dans le dépistage 

précoce, la prévention, le diagnostic et le traitement des maladies, et 

contribuent en tant que tels à améliorer la santé et la qualité de vie de 

l'individu. Fortement axée sur la recherche, Roche est l'un des leaders 

mondiaux sur le marché des produits pour diagnostic et le premier fournisseur 

de médicaments destinés aux domaines de la cancérologie et de la 

médecine de transplantation. Roche occupe également une position de 

premier plan en virologie. En 2005, le chiffre d'affaires de la division Pharma 

s'est élevé à 27,3 milliards de francs suisses, la division Diagnostics ayant 

quant à elle réalisé un chiffre d'affaires de 8,2 milliards de francs suisses. 

Roche emploie quelque 70 000 personnes dans 150 pays. Elle entretient des 

liens de R&D et a conclu des alliances stratégiques avec de nombreux 

partenaires; elle détient notamment une participation majoritaire dans 

Genentech et Chugai. Pour de plus amples informations sur le groupe 

Roche, consulter son site internet (www.roche.com). 

Roche 

52, boulevard du Parc 

92521 Neuilly-sur-Seine Cedex 

Tél. : + 33 (0) 01 46 40 50 00 

Fax : + 33 (0) 01 46 40 52 83 

www.roche.fr 


SANOFI-AVENTIS FRANCE 

Sanofi-aventis est le troisième groupe pharmaceutique mondial et le numéro 1 en 

Europe. Le groupe sanofi-aventis s'appuie sur une recherche internationale pour 

se développer dans 7 domaines thérapeutiques majeurs : le cardiovasculaire, la 

thrombose, le cancer, les maladies métaboliques, le système nerveux central, la 

médecine interne et les vaccins. 

Sanofi-aventis is the world's 3 rd largest pharmaceutical company and ranks 

number 1 in Europe, with around 100,000 employees worldwide 

Sanofi-aventis focuses its activities on seven major therapeutic areas: 

cardiovascular, thrombosis, oncology, internal medicine, metabolic disorders, 

diseases of the central nervous system and vaccines 

Sanofi-aventis France 

9, boulevard Romain Rolland 

75159 Paris cedex 14 

Tél. : +33 (0)1 57 63 33 33 

Fax : +33 (0)1 57 63 08 30 

www.sanofi-aventis.fr 


Putting knowledge into practice 

VIRCO BVBA 

Pioneers in the science of HIV drug resistance, we provide the most reliable, 

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Notre savoir mis en pratique 

En tant que pionniers dans la science de la résistance aux traitements 

antirétroviraux, nous fournissons les analyses les plus fiables, les plus 

avantageuses du point de vue coût-qualité et les plus pratiques qui soient 

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personnes infectées par le VIH. 

VirtualPhenotype donne une analyse phénotypique en combinaison avec 

un rapport génotypique, afin de fournir un profil complet de la résistance 

virale. 

Antivirogram ® est le seul test phénotypique qui ait été validé au cours d'un 

essai prospectif. Le test fournit une mesure directe de la résistance. 

Virco fournit des outils essentiels pour améliorer la prise en charge 

thérapeutique des personnes infectées par le VIH. 

Virco BVBA 

General de Wittelaan L 11B4 

2800 mechelen 

BELGIUM 

Tél. : +32-15-285-300 

www.vircolab.com 


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