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 whether the other major aspect of virus dynamics, viral replicative capacity, does change.In vitrowork has indicated that the viral replicative capacity increases butin vivoevidence has been lacking.Methods:As anin vivomeasure of the viral replicative capacity, we studied the rate of rebound of plasma HIV RNA level during a 1-week therapy interruption in previously untreated patients who had received 2 weeks of antiretroviral therapy.Results:Such therapy in five previously drug-naive patients with high CD4 lymphocyte counts (mean, 611×106/l) and five patients with low counts (mean, 49×106/l) led to a mean 2.2log10copies/ml decrease in plasma HIV-1 levels (from 5-6log10copies/ml) in 2 weeks. This was similar in the two groups. Interruption of therapy for the ensuing week resulted in a stable HIV-1 level for approximately 2 days followed by a rebound towards pretherapy level, which was much more marked in the patients with low CD4 cell counts (estimated mean rise 2.22log10versus 1.06log10copies/ml;P<0.02). After restarting therapy, HIV RNA levels returned to pre-interruption levels.Conclusions:These findings need confirmation, but the ability of HIV-1 to replicatein vivoappears to increase during HIV-1 infection. This increased replicative capacity, for which there are several potential explanations, may be the cause of gradual CD4 lymphocyte depletion.