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2nd International AIDS Society Conference on HIV Pathogenesis and TreatmentParis, France - July 13 - 16, 2003 |
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 147
Antiviral Therapy 2003; 8(Suppl. 1):S219
[ABSTRACT:] In this study, we examined the relationship between ex vivo HIV-1 fitness and viral genetic diversity during the course of HIV-1 disease. Primary HIV-1 isolates were propagated from at least three blood samples collected over a period of 2–5 years in eight patients. A relative fitness value for each patient HIV-1 isolate was calculated from competitions with four control HIV-1 strains in peripheral blood mononuclear cell (PBMC) cultures. The genetic diversity of the HIV-1 quasispecies and divergence from the virus at the earliest timepoint was estimated by sequencing the C2-C3 env region of at least ten HIV-1 clones from the same patient samples used to propagate virus. In absence of ARV treatment, patient HIV-1 isolates gained fitness over the course of disease at the same rate as the increase in HIV-1 env diversity. A loss in both fitness and quasispecies diversity was observed upon the initiation of antiretroviral therapy. However, fitness and diversity slowly rebounded during the course of treatment even though ARV resistance mutations were not selected. In both untreated and treated patients, variations in quasispecies diversity appeared to correspond to respective changes in ex vivo viral fitness with a positive correlation between diversity and fitness (r=0.692, P=0.0119). A negative correlation was observed when comparing fitness to CD4 cell counts in each individual patient and in the entire patient cohort (r=–0.722, P=0.0052). These data provide the first in vivo evidence that increases in HIV-1 fitness may be related to increasing viral load and quasispecies diversity.
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Copyright © 2003 - International AIDS Society (IAS) and International Medical Press (IMP). Reproduction courtesy of International Medical Press.