title: The decay of the latent reservoir of replication-competent HIV-1 is inversely correlated with the extent of residual viral replication during prolonged anti-retroviral therapy.
abstract: Replication-competent HIV-1 can be isolated from infected patients despite prolonged plasma virus suppression by anti-retroviral treatment. Recent studies have identified resting, memory CD4+ T lymphocytes as a long-lived latent reservoir of HIV-1 (refs. 4,5). Cross-sectional analyses indicate that the reservoir is rather small, between 103 and 107 cells per patient. In individuals whose plasma viremia levels are well suppressed by anti-retroviral therapy, peripheral blood mononuclear cells containing replication-competent HIV-1 were found to decay with a mean half-life of approximately 6 months, close to the decay characteristics of memory lymphocytes in humans and monkeys. In contrast, little decay was found in a less-selective patient population. We undertook this study to address this apparent discrepancy. Using a quantitative micro-culture assay, we demonstrate here that the latent reservoir decays with a mean half-life of 6.3 months in patients who consistently maintain plasma HIV-1 RNA levels of fewer than 50 copies/ml. Slower decay rates occur in individuals who experience intermittent episodes of plasma viremia. Our findings indicate that the persistence of the latent reservoir of HIV-1 despite prolonged treatment is due not only to its slow intrinsic decay characteristics but also to the inability of current drug regimens to completely block HIV-1 replication.
authors.affiliation: Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, New York, New York 10016, USA.
authors.forename: B
authors.initials: B
authors.lastname: Ramratnam
authors.forename: J E
authors.initials: JE
authors.lastname: Mittler
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: D
authors.initials: D
authors.lastname: Boden
authors.forename: A
authors.initials: A
authors.lastname: Hurley
authors.forename: F
authors.initials: F
authors.lastname: Fang
authors.forename: C A
authors.initials: CA
authors.lastname: Macken
authors.forename: A S
authors.initials: AS
authors.lastname: Perelson
authors.forename: M
authors.initials: M
authors.lastname: Markowitz
authors.forename: D D
authors.initials: DD
authors.lastname: Ho
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D018451:Homosexuality, Male; D006801:Humans; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016602:Needlestick Injuries; D012367:RNA, Viral / Q000097:blood; D013997:Time Factors; D019562:Viral Load; D017735:Virus Latency; D014779:Virus Replication
chemical_list: D012367:RNA, Viral