In vivo HIV-1 replicative capacity in early and advanced infection

Objective: Previous studies on patients treated with potent antiretroviral therapy have shown that viral clearance rates do not tend to change between early and advanced HIV-1 infection. Our objective was to investigate wheth er the other major aspect of virus dynamics, viral replicative capacity, do es change. In vitro work has indicated that the viral replicative capacity increases but in vivo evidence has been lacking. Methods: As an in vive measure of the viral replicative capacity, we studie d the rate of rebound of plasma HIV RNA level during a 1-week therapy inter ruption in previously untreated patients who had received 2 weeks of antire troviral therapy. Results: Such therapy in five previously drug-naive patients with high CD4 lymphocyte counts (mean, 611 x 10(6)/l) and five patients with low counts ( mean, 49 x 10(6)/l) led to a mean 2.2 log(10) copies/ml decrease in plasma HIV-1 levers (from 5-6 log(10) copies/ml) in 2 weeks. This was similar in t he two groups. Interruption of therapy for the ensuing week resulted in a s table HIV-1 level for approximately 2 days followed by a rebound towards pr etherapy level, which was much more marked in the patients with low CD4 cel l counts (estimated mean rise 2.22 log(10) versus 1.06 log(10) copies/ml; P < 0.02). After restarting therapy, HIV RNA levels returned to pre-interrup tion levels. Conclusions: These findings need confirmation, but the ability of HIV-1 to replicate in vive appeals to increase during HIV-1 infection. This increase d replicative capacity, for which there are several potential explanations, may be the cause of gradual CD4 lymphocyte depletion. (C) 1999 Lippincott Williams & Wilkins.