Rate of HIV-1 decline following antiretroviral therapy is related to viral load at baseline and drug regimen

Objectives and design: The dynamics of viral decline following the initiation of antiretroviral treatment were studied in 29 HIV-1-infected patients participating in a two-arm trial comparing immediate (group A: ritonavir, zidovudine and lamivudine) and delayed (group B: ritonavir supplemented by zidovudine and lamivudine on day 21) triple therapy. Parameters underlying viral dynamics were estimated using mathematical models tailored to these treatment protocols. Results: The decline in plasma HIV-1 density between day 0 and 21 was steeper in group A (-2.27 ± 0.46 log10) than group B (-1.87 ± 0.56 log10). In a subset of patients amenable to full mathematical analysis, a short-lived productively infected cell compartment (producing ~ 97% of total virions) decayed with a half-life of 1.0-2.5 days, whereas a long-lived infected cell compartment decayed with a halflife of 18.8-32.8 days. Estimates for the time for the elimination of virus from these two cell populations ranged from 474 to 802 days. The rate of loss of productively infected CD4+ T cells was positively correlated with baseline viral load in group A and in the combined dataset. Conclusions: These results suggest that HIV-infected cell populations may have a faster turnover in patients with higher viral loads due to higher infection rate parameters, higher rates of virus production, or lower virus clearance rates.