Circulating HIV-1-infected cell burden from seroconversion to AIDS: importance of postseroconversion viral load on disease course

Abstract

The purpose of this study was to characterize quantitative changes in circulating infected cells over the natural history of human immunodeficiency virus (HIV) disease in relation to clinical/immunological outcome. HIV-1 gag DNA polymerase chain reaction (PCR) and peripheral blood mononuclear cell (PBMC) co-cultures were performed on limiting dilutions of cryopreserved PBMC from specimens collected at enrollment and after 5 years of follow-up from nine seropositive subjects classified as rapid progressors, nine intermediate progressors, and 10 nonprogressors. Limiting dilution PCR was also performed on serial pre/postseroconversion specimens from 18 seroconvertors. By quantitative DNA PCR analysis, the infected cell burden was significantly higher at enrollment in the RP [mean of 330 PCR units (PCRU)/10(6) PBMCs] than in the IP (160 PCRU/10(6) PBMCs) and NP (73 PCRU/10(6) PBMCs) groups (p = 0.05). When results were analyzed on an individual level with proportional hazard regression, baseline PCRU (p = 0.05) and CD4 slope (p = 0.0007) were significantly associated with developing acquired immune deficiency syndrome (AIDS) in 5 years, but baseline tissue culture infectious units (TCIU) was not. The increase in PCR-positive cells after 5 years was modest in all three groups (two- to fivefold), whereas the proportion of PCR-positive cells that yielded virus in culture increased significantly (21- to 31-fold) over time in all three groups. Infected cell burden in postseroconversion specimens was relatively stable within each subject, but varied greatly (from 1.6 to 1,024 PCRU/10(6) PBMCs) among subjects.(ABSTRACT TRUNCATED AT 250 WORDS)