title: Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy.
abstract: Although highly active antiretroviral therapy (HAART) in the form of triple combinations of drugs including protease inhibitors can reduce the plasma viral load of some HIV-1-infected individuals to undetectable levels, it is unclear what the effects of these regimens are on latently infected CD4+ T cells and what role these cells play in the persistence of HIV-1 infection in individuals receiving such treatment. The present study demonstrates that highly purified CD4+ T cells from 13 of 13 patients receiving HAART with an average treatment time of 10 months and with undetectable (<500 copies HIV RNA/ml) plasma viremia by a commonly used bDNA assay carried integrated proviral DNA and were capable of producing infectious virus upon cellular activation in vitro. Phenotypic analysis of HIV-1 produced by activation of latently infected CD4+ T cells revealed the presence in some patients of syncytium-inducing virus. In addition, the presence of unintegrated HIV-1 DNA in infected resting CD4+ T cells from patients receiving HAART, even those with undetectable plasma viremia, suggests persistent active virus replication in vivo.
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. twchun@nih.gov
authors.forename: T W
authors.initials: TW
authors.lastname: Chun
authors.forename: L
authors.initials: L
authors.lastname: Stuyver
authors.forename: S B
authors.initials: SB
authors.lastname: Mizell
authors.forename: L A
authors.initials: LA
authors.lastname: Ehler
authors.forename: J A
authors.initials: JA
authors.lastname: Mican
authors.forename: M
authors.initials: M
authors.lastname: Baseler
authors.forename: A L
authors.initials: AL
authors.lastname: Lloyd
authors.forename: M A
authors.initials: MA
authors.lastname: Nowak
authors.forename: A S
authors.initials: AS
authors.lastname: Fauci
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D004279:DNA, Viral; D015726:Giant Cells; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D017735:Virus Latency; D014779:Virus Replication
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral