title: 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)
authors.affiliation: Irwin Memorial Blood Centers, San Francisco, CA 94118-4496.
authors.forename: T H
authors.initials: TH
authors.lastname: Lee
authors.forename: H W
authors.initials: HW
authors.lastname: Sheppard
authors.forename: M
authors.initials: M
authors.lastname: Reis
authors.forename: D
authors.initials: D
authors.lastname: Dondero
authors.forename: D
authors.initials: D
authors.lastname: Osmond
authors.forename: M P
authors.initials: MP
authors.lastname: Busch
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000382:microbiology*; D015496:CD4-Positive T-Lymphocytes; D015331:Cohort Studies; D015925:Cryopreservation; D004279:DNA, Viral / Q000097:blood; D006679:HIV Seropositivity / Q000276:immunology / Q000382:microbiology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000382:microbiology*; D008137:Longitudinal Studies; D008297:Male; D016133:Polymerase Chain Reaction; D016016:Proportional Hazards Models; D011533:Proviruses / Q000235:genetics / Q000276:immunology / Q000502:physiology; D015203:Reproducibility of Results; D014766:Viremia / Q000276:immunology / Q000382:microbiology
chemical_list: D004279:DNA, Viral