Quantitative Assessment of HIV Replication and Variation In Vivo: Relevance toDisease Pathogenesis and Response to Therapy

摘要

The pathogenesis of HIV-1 disease is driven by continuous rounds of viralreplication in lymphoreticular tissues. Plasma virus load is believed to reflect virus production in these tissue site but the dynamics and quantitative relationships between virus populations the blood and lymphoid tissues remain to be determined. In the studies described, we have developed quantitative approaches for evaluating plasma viral RNA content and composition. We show that plasma viral RNA is virion-associated, is correlated with plasma viral p24 antigen and infectivity titers, and can be accurately quantified by RT-PCR and branched DNA (bDNA) signal amplification assays. Furthermore, we show that initiation of potent antiretroviral therapy, or initiation of a cytotoxic T-lymphocyte (CTL) response in primary (acute) infection, leads to rapid declines in plasma virus load and replacement of wild-type virus populations by escape variants. Importantly, the studies show for the first time that virus-specific CTL exert a biologically significant suppressive effect on UrV-l replication in vivo, comparable in magnitude to the effects of antiretroviral chemotherapy.