RATE OF HIV-1 DECLINE FOLLOWING ANTIRETROVIRAL THERAPY IS RELATED TO VIRAL LOAD AT BASE-LINE AND DRUG REGIMEN

Objectives and design: The dynamics of viral decline following the ini tiation of antiretroviral treatment were studied in 29 HIV-l-infected patients participating in a two-arm trial comparing immediate (group A : ritonavir, zidovudine and lamivudine) and delayed (group B: ritonavi r supplemented by zidovudine and lamivudine on day 21) triple therapy. Parameters underlying viral dynamics were estimated using mathematica l models tailored to these treatment protocols. Results: The decline i n plasma HIV-1 density between day 0 and 21 was steeper in group A (-2 .27 +/- 0.46 log(10)) than group B (-1.87 +/- 0.56 log(10)). In a subs et of patients amenable to full mathematical analysis, a short-lived p roductively infected cell compartment (producing similar to 97% of tot al virions) decayed with a half-life of 1.0-2.5 days, whereas a long-l ived infected cell compartment decayed with a half-life of 18.8-32.8 d ays. Estimates for the time for the elimination of virus from these tw o cell populations ranged from 474 to 802 days. The rate of loss of pr oductively infected CD4+ T cells was positively correlated with baseli ne viral load in group A and in the combined dataset. Conclusions: The se results suggest that HIV-infected cell populations may have a faste r turnover in patients with higher viral loads due to higher infection rate parameters, higher rates of virus production, or lower virus cle arance rates. (C) 1998 Lippincott-Raven Publishers.