title: Strong cell-mediated immune responses are associated with the maintenance of low-level viremia in antiretroviral-treated individuals with drug-resistant human immunodeficiency virus type 1.
abstract: Antiretroviral (ARV)-treated patients often maintain low to moderate levels of viremia, despite the emergence of drug-resistant human immunodeficiency virus (HIV). We studied host and viral factors that may contribute to the control of viral replication in a cohort of 189 adults. Among ARV-treated patients with detectable viremia, there was a bell-shaped relationship between Gag-specific CD4+ T cell responses and viremia, with the highest cellular immune responses observed in patients with plasma HIV RNA levels of 1000-10,000 copies/mL. In contrast, there was a negative association between Gag-specific CD4+ T cell responses and viremia among ARV-untreated individuals with wild-type HIV. Strong cellular immune responses among individuals with drug-resistant HIV predicted subsequent lack of virological progression. Finally, there was a positive correlation between replicative capacity and viremia. Collectively, these data suggest that the selection of drug-resistance mutations may reduce the pathogenic potential of HIV, which leads to a balanced state of enhanced cellular immunity and low-level viremia.
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, California, USA. sdeeks@php.ucsf.edu
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Martin
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sinclair
authors.forename: Jeff
authors.initials: J
authors.lastname: Harris
authors.forename: Torsten B
authors.initials: TB
authors.lastname: Neilands
authors.forename: Holden T
authors.initials: HT
authors.lastname: Maecker
authors.forename: Elilta
authors.initials: E
authors.lastname: Hagos
authors.forename: Terri
authors.initials: T
authors.lastname: Wrin
authors.forename: Christos J
authors.initials: CJ
authors.lastname: Petropoulos
authors.forename: Barry
authors.initials: B
authors.lastname: Bredt
authors.forename: Joseph M
authors.initials: JM
authors.lastname: McCune
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015331:Cohort Studies; D024882:Drug Resistance, Viral; D015683:Gene Products, gag / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D011446:Prospective Studies; D011498:Protein Precursors / Q000276:immunology; D012367:RNA, Viral / Q000097:blood; D014766:Viremia / Q000276:immunology*; D014779:Virus Replication
chemical_list: D019380:Anti-HIV Agents; D015683:Gene Products, gag; D011498:Protein Precursors; D012367:RNA, Viral; C059767:p55 gag precursor protein, Human immunodeficiency virus 1