title: HIV-infected individuals receiving effective antiviral therapy for extended periods of time continually replenish their viral reservoir.
abstract: The persistence of latently infected, resting CD4+ T cells is considered to be a major obstacle in preventing the eradication of HIV-1 even in patients who have received effective antiviral therapy for an average duration of 5 years. Although previous studies have suggested that the latent HIV reservoir in the resting CD4+ T cell compartment is virologically quiescent in the absence of activating stimuli, evidence has been mounting to suggest that low levels of ongoing viral replication persist and in turn, prolong the overall half-life of HIV in patients receiving antiviral therapy. Here, we demonstrate the persistence of replication-competent virus in CD4+ T cells in a cohort of patients who had received uninterrupted antiviral therapy for up to 9.1 years that rendered them consistently aviremic throughout that time. Surprisingly, substantially higher levels of HIV proviral DNA were found in activated CD4+ T cells when compared with resting CD4+ T cells in the majority of patients we studied. Phylogenetic analyses revealed evidence for cross infection between the resting and activated CD4+ T cell compartments, suggesting that ongoing reactivation of latently infected, resting CD4+ T cells and spread of virus by activated CD4+ T cells may occur in these patients. Such events may allow continual replenishment of the CD4+ T cell reservoir and resetting of the half-life of the latently infected, resting CD4+ T cells despite prolonged periods of aviremia.
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892, USA. twchun@nih.gov
authors.forename: Tae-Wook
authors.initials: TW
authors.lastname: Chun
authors.forename: David C
authors.initials: DC
authors.lastname: Nickle
authors.forename: J Shawn
authors.initials: JS
authors.lastname: Justement
authors.forename: Danielle
authors.initials: D
authors.lastname: Large
authors.forename: Alice
authors.initials: A
authors.lastname: Semerjian
authors.forename: Marcel E
authors.initials: ME
authors.lastname: Curlin
authors.forename: M Angeline
authors.initials: MA
authors.lastname: O'Shea
authors.forename: Claire W
authors.initials: CW
authors.lastname: Hallahan
authors.forename: Marybeth
authors.initials: M
authors.lastname: Daucher
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Ward
authors.forename: Susan
authors.initials: S
authors.lastname: Moir
authors.forename: James I
authors.initials: JI
authors.lastname: Mullins
authors.forename: Colin
authors.initials: C
authors.lastname: Kovacs
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Fauci
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D006678:HIV / Q000187:drug effects* / Q000378:metabolism; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D013997:Time Factors; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents