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

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

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

AIDS. 1999 Jan 14;13(1):67-73. Unique Identifier : AIDSLINE MED/99223953
Phillips AN; McLean AR; Loveday C; Tyrer M; Bofill M; Devereux H; Madge S; Dykoff A; Drinkwater A; Burke A; Huckett L; Janossy G; Johnson MA; Royal Free Centre for HIV Medicine, Department of Primary Care; and Population Sciences, Royal Free and University College; Medical School, London, UK.

Abstract: 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 vitro work has indicated that the viral replicative, capacity increases but in vivo evidence has been lacking. METHODS: As an in vivo measure 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 x 10(6)/l) and five patients with low counts (mean, 49 x 10(6)/l) led to a mean 2.2 log10 copies/ml decrease in plasma HIV-1 levels (from 5-6 log10 copies/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 2.22 log10 versus 1.06 log10 copies/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 replicate in vivo appears 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.

Keywords: JOURNAL ARTICLE Human HIV Infections/DRUG THERAPY/IMMUNOLOGY/PHYSIOPATHOLOGY/*VIROLOGY HIV-1/GENETICS/*PHYSIOLOGY Support, Non-U.S. Gov't *Virus Replication
990930
A9991340

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