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European Journal of Medical Research - Deutsche AIDS ...

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June 27, 2007 EUROPEAN JOURNAL OF MEDICAL RESEARCH<br />

27<br />

following a list <strong>of</strong> resistance associated mutations proposed<br />

by Bennet et al. (13th CROI; 2006). This algorithm classifies<br />

mutations as resistance relevant, which meet the following<br />

criteria: Mutations should be associated with HIV drug resistance<br />

and selected by ART, non-polymorph and applicable<br />

to all subtypes. Results <strong>of</strong> both methods were compared.<br />

Non-B subtypes were additionally analysed with NCBI subtype<br />

tool.<br />

Results: The following subtypes were determined: B (212;<br />

80%), A (6; 2.3%), D (12; 4.5%), C (4; 1.5%), G (2; 0.8%), K<br />

(1; 0.4%), CRF02_AG (10; 3.8%), CRF01_AE (10; 3.8%),<br />

CRF05_DF (2; 0.8%), CRF06_CPX (2; 0.8%), CRF08 (1;<br />

0.4%), PR:F/RT:B (2; 0.8%) and 14BG (1; 0.4%)(Table1).<br />

Conclusion: In this study the prevalence <strong>of</strong> primary resistance<br />

in Germany is 10.2% (Stanford) or 8.7% (Bennett). The<br />

results <strong>of</strong> the two different algorithms differ slightly, due to<br />

the fact that Stanford db regards other additional secondary<br />

mutations and thus found more isolates with PI mutations<br />

than Bennett. Most resistance mutations were found against<br />

NRTIs and least against PIs. 2% <strong>of</strong> all patients have resistance<br />

mutations against more than one drug-class. The analysis <strong>of</strong><br />

HIV-Subtype becomes more important in Germany, since<br />

every fifth patient is infected with HIV non-B subtype.<br />

A.4 (Poster)<br />

Establishing large-scale cohorts in Africa to<br />

prepare for HIV vaccine efficacy trials<br />

Price M. 1 , Kamali A. 2 , Karita E. 3 , Anzala O. 4 ,<br />

Mwangome M. 5 , Sanders E. 6 , Bekker L. 7 , Gilmour J. 8 ,<br />

Fast P. 8 , Amornkul P. 9 , Stevens G. 8 , Imambao M. 10 ,<br />

Kenkewa W. 10 , Middlekoop K. 7 , Ruzagira E. 2 ,<br />

Kayitenkore K. 11 , Vwalika C. 10 , Lakhi S. 10 , Mutua G. 4 ,<br />

Byabagambi J. 2 , Kebba A. 2<br />

1 International Aids Vaccine Initiative, R&D, San Mateo,<br />

United States <strong>of</strong> America, 2 Med Res Council/Uganda Virus<br />

Res Inst, Masaka and Entebbe, Entebbe, Uganda, 3 Rwanda<br />

Zambia HIV Res Group, Kigali and Lusaka, Lusaka, Zambia,<br />

4 Kenya Aids Vaccine Initiative, Nairobi, Kenya, 5 Kenya<br />

<strong>Medical</strong> <strong>Research</strong> Institute, Kifili, Kenya, 6 Oxford University,<br />

Oxford, United Kingdom, 7 Univ <strong>of</strong> Cape Town, Desmond<br />

Tutu HIV Ctr, Cape Town, South Africa, 8 International Aids<br />

Vaccine Initiative, New York, United States <strong>of</strong> America,<br />

9 International Aids Vaccine Initiative, Nairobi, Kenya,<br />

10 Rwanda Zambia HIV Res Group, Kigali and Lusaka, Kigali,<br />

Rwanda, 11 Rwanda Zambia HIV Res Group, Kigali and<br />

Lusaka, Kifili, Rwanda<br />

Objectives: To develop cohorts and collect data on HIV-related<br />

risk behaviors, HIV incidence, cohort recruitment and<br />

retention for future HIV vaccine efficacy trials.<br />

Methods: Since 2004, eight sites in east and southern Africa<br />

have developed clinical, laboratory, and counseling capacity<br />

to prepare for large-scale HIV vaccine trials in collaboration<br />

with IAVI. After providing informed consent, adult, HIV-negative<br />

potential trial volunteers are recruited, receive HIV voluntary<br />

counseling and testing, and are followed quarterly. Demographic<br />

and risk behavior data are collected through structured<br />

questionnaires; specimens are collected for HIV-testing.<br />

Table1. 4 two-class resistances and 1<br />

triple-class resistance were found.<br />

Volunteers who become HIV-infected are followed to collect<br />

viral and immunopathogenesis information on early HIV infection.<br />

All sites operate according to good clinical and laboratory<br />

practices.<br />

Results: As <strong>of</strong> January 2007, 5,615 at-risk volunteers are enrolled:<br />

2,783 (50%) HIV-discordant couples, 1184 (21%) rural<br />

residents in high HIV-prevalence area, 178 (3%) men who<br />

have sex with men (MSM), and 1,196 (21%) other at-risk participants.<br />

With over 8,500 person-years <strong>of</strong> observation (PY),<br />

HIV incidence in sites with more than 100 PY ranged from<br />

1.0 to 11.3 cases/100 PY. Despite shorter duration <strong>of</strong> followup,<br />

MSM have the highest incidence, 8.2 cases/100PY. Over<br />

160 volunteers with a documented duration <strong>of</strong> HIV-infection<br />

<strong>of</strong> less than 385 days are being followed.<br />

Conclusions: Eight sites in sub-Saharan Africa have successfully<br />

engendered research facilities capable <strong>of</strong> recruiting thousands<br />

<strong>of</strong> potential volunteers for vaccine clinical trials. The<br />

lessons learned from this work will guide the development <strong>of</strong><br />

upcoming efficacy trials.<br />

A.5 (Vortrag)<br />

Entwicklung von Morbidität und Mortalität in der<br />

Frankfurter Kohorte<br />

Stephan C. 1 , Khaykin P. 1 , Staszewski S. 1 , Klauke S. 2 ,<br />

Gute P. 3 , Helm E.B. 1<br />

1 HIVCENTER, Klinikum der Johann Wolfgang Goethe-<br />

Universität, Frankfurt, Germany, 2 IFS Praxis Stresemannallee,<br />

Frankfurt, Germany, 3 HIV Schwerpunkt-Praxis<br />

Friedensstrasse, Frankfurt, Germany<br />

Ziel: Identifikation von Trends in der HIV-Epidemiologie anhand<br />

einer Kohorte.<br />

Methodik: Analyse von Morbiditätsfaktoren und Mortalität<br />

bei 9000 HIV-infizierten Patienten der Frankfurter Kohorte ab<br />

1982.<br />

Ergebnis: Bis Ende des Jahres 2006 waren im untersuchten<br />

Kollektiv rund 2900 Patienten an <strong>AIDS</strong> erkrankt. Insgesamt<br />

sind bis Ende 2006 ca. 1900 gestorben, 320 vor Erreichen des<br />

Stadiums <strong>AIDS</strong>. Seit 1996 wird ein kontinuierlicher Rückgang<br />

der <strong>AIDS</strong>-Inzidenz in der Kohortenpopulation beobachtet.<br />

Der Anteil der Frauen beträgt in den letzten Jahren nahezu<br />

unverändert 20-25%. Die Zahl der Erstvorstellung i.v.-Drogenabhängiger<br />

Patienten hat seit dem Jahr 2000 deutlich<br />

abgenommen, nicht aber der Anteil an den <strong>AIDS</strong>-Patienten<br />

des Gesamtkollektivs. Der Anteil der Migranten aus Endemiegebieten<br />

an den HIV-Infizierten hat seit Mitte der<br />

1990er Jahre zugenommen, heute hat jeder vierte Patient der<br />

Frankfurter Kohorte einen Migrationshintergrund. Unter den<br />

<strong>AIDS</strong>-definierenden Erkrankungen sind klassische Diagnosen<br />

wie PCP und Kaposi-Sarkom seltener geworden, während<br />

maligne Lymphome und Tuberkulose zunehmen. Unter den<br />

Todesursachen sind die <strong>AIDS</strong>-definierenden Erkrankungen<br />

seltener; zunehmend werden kardiovaskuläre und onkologische<br />

Erkrankungen beobachtet; dem zahlenmäßigen Rückgang<br />

der i.v.-Drogenabhängigen unter den <strong>AIDS</strong>-Patienten folgend,<br />

nimmt auch die Todesursache Leberzirrhose in den letzten<br />

beiden Jahren wieder ab.

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