European Journal of Medical Research - Deutsche AIDS ...

June 27, 2007 EUROPEAN JOURNAL OF MEDICAL RESEARCH
15
bedrohliche Langzeittoxizitäten sind somit ebensolche hypothetischen
Risiken wie die Risiken eines (früheren) Therapieversagens.
Zu guter Letzt darf der Patientenwille zu einer
Monotherapie nicht geringer wiegen als das Dogma einer
Leitlinie. Dort wo Evidenz fehlt, gilt für den Arzt das "primum
nihil nocere". Diesem Grundsatz ist die Monotherapie alle
Male näher als die Kombination mehrerer Substanzen.
B.ER.7
Gene therapy for HIV-infection
van Lunzen J. 1 , Glaunsinger T. 1 , Hermann F. 2 , Egerer L. 2 ,
Newrzela S. 2 , Kimpel J. 2 , von Laer D. 2
1 Universitätskrankenhaus Eppendorf, Infektiologie, Hamburg,
Germany, 2 Georg-Speyer-Haus, Frankfurt am Main, Germany
Drug toxicity and viral resistance limit long-term efficacy of
antiviral drug treatment for HIV infection. Thus, alternative
therapies need to be explored. Here, we tested the infusion of T
lymphocytes transduced with a retroviral vector (M87o) that
expresses an HIV entry inhibitory peptide (maC46). Genemodified
autologous T cells were infused into 10 HIV-infected
patients with advanced disease and multidrug resistant virus
during antiretroviral combination therapy. T cell infusions were
tolerated well with no severe side effects. A significant increase
of CD4 counts was observed post infusion. At the end of
the one-year follow-up, the CD4 counts of all patients were still
around or above baseline. Gene-modified cells could be detected
in peripheral blood, lymph nodes and bone marrow throughout
the one-year follow-up, whereby marking levels correlated
with the cell dose. No significant changes of viral load were
observed during the first four months. Four of the seven patients
that changed their antiviral drug regimen thereafter responded
with a significant decline in plasma viral load. In conclusion,
the transfer of gene-modified cells was safe, led to sustained
levels of gene marking and may improve immune competence
in HIV-infected patients with advanced disease and
multidrug resistant virus. However, the low level of gene marking
and the lack of a substantial in vivo accumulation of geneprotected
cells induced us to return to the bench and further improve
our strategy. Different configurations of gammaretroviral
SIN vectors were cloned and analyzed for improved long-term
expression in vivo in mouse T-cell and stem-cell transplantation
models. In addition, several variants of the M87o transgenes
were generated that lead to shedding/secretion of the antiviral
C peptide and thus protect non-gene-modified cells in
the vicinity. Finally, several humanized mouse models were
compared for their suitability for preclinical testing of gene
therapy regimen for HIV infection.
B.ER.8
European study about mitochondrial toxicity in
HIV-negative children born to HIV-1 infected
mothers (MITOC)
Buchholz B. 1 , Wintergerst U. 2 , Brockmeyer N. 3 ,
Competence Network for HIV/AIDS and MITOC
1 Kindermodul, Universitätskinderklinik Mannheim,
Mannheim, Germany, 2 Kindermodul, Dr.von Haunersches
Kinderspital, München, Germany, 3 Dermatologische Klinik
der Ruhr Universität, St. Josef Hospital, Bochum, Germany
In Europe the low rate (1-2%) of vertical transmission of
HIV1 in pregnant women has been achieved by the combination
of anti-retroviral therapy of these women (including nucleoside
reverse transcriptase inhibitors/NRTI), caesarean
section, anti-retroviral post exposition prophylaxis (with
NRTI) in the newborn and refraining from breast-feeding. Mitochondrial
toxicity in children associated with in utero/postnatal
exposure to NRTIs (as cause of affinity for mitochondrial
g-DNA polymerase inducing mitochondrial depletion/dysfunction)
was recovered during a screening in the French
Perinatal Cohort in 1999+2003: The estimated incidence of
mitochondrial dysfunction up to the age of 18 months was
0.26% (95% confidence interval, 0.10-0.54) among these
NRTI-exposed children, of whom 21/2644 had established or
possible mitochondrial dysfunction. In April 2001 the Pharmacovigilance
Working Party of the European Committee for
Medicinal Products for Human Use requested further investigation
of mitochondrial toxicity in children associated with in
utero/postnatal exposure to NRTIs. Accordingly the Collaborative
Committee for Mitochondrial Toxicity in Children (MI-
TOC) with representatives from all companies distributing
NRTIs(BMS, Gilead Sciences, GSK) and from European cohorts
collecting prospective data on these children (French
Perinatal Cohort Study, Spanish Perinatal Cohort Study,
Swiss Mother and Children HIV Cohort Study, Italian Register
for HIV Infection in Children, German Competence Network
for HIV/AIDS) was established. In the protocol developed
by MITOC these children will be examined in a crosssectional
evaluation at a single visit between the ages of 18-
24 months
- to determine the prevalence of neurological symptoms of
cognitive or motor delay (=cases)
- to categorize these cases into explained and unexplained
neurological symptoms
- to estimate the proportion of the unexplained cases whose
symptoms are suggestive of mitochondrial disorder
- to assess the association between type, duration of ART exposure
in utero and/or postnatally and unexplained mitochondrial
disorder-related cognitive/motor delay. Based upon information
provided by the cohorts/studies, the study will enroll
approximately 2500 to 3000 eligible children over a twoyear
period.
B.ER.9
Herabgesetzte periphere Nervenregeneration in
HIV-Patienten nach experimenteller Denervierung
Hahn K. 1 , Brown A. 2 , Hauer P. 2 , McArthur J.C. 2 ,
Polydefkis M. 2
1 Charité, Humboldt Universität Berlin, Neurologie, Berlin,
Germany, 2 Johns Hopkins Universität, Neurologie, Baltimore,
United States of America
Die HIV-assoziierte sensorische Neuropathie (HIV-SN) ist
die häufigste neurologische Komplikation der HIV-Erkrankung.
Ziel der Studie war es, zu untersuchen ob Patienten
mit HIV-Erkrankung Störungen der peripheren Nervenregeneration
aufweisen. Dazu untersuchten wir die epidermale
Nervenfaserregeneration nach experimenteller mechanischer
und chemischer Denervation in Hautstanzbiopsiemodellen in
gesunden Kontrollprobanden und Probanden mit HIV-Erkrankung.
Methodik: Die chemische Axotomie erfolgte durch topische
Capsaicinapplikation am distalen lateralen Oberschenkel in
71 Kontrollen und 22 HIV-positiven Probanden. Über den
Zeitraum von 100 Tagen wurde die Nervenfaserregeneration