title: Changes in Markers of T-Cell Senescence and Exhaustion With Atazanavir-, Raltegravir-, and Darunavir-Based Initial Antiviral Therapy: ACTG 5260s.
abstract: It is unclear whether differential roles of CD4(+) versus CD8(+) T-cell senescence/exhaustion and effects of antiretroviral therapy (ART) on these processes may contribute to morbidity in treated human immunodeficiency virus type 1 (HIV) infection. In a prospective 96-week trial, 328 HIV-infected ART-naive participants were randomly assigned to receive tenofovir-emtricitabine plus either atazanavir/ritonavir, darunavir/ritonavir, or raltegravir. Markers of CD4(+) T-cell senescence (ie, the percentage of CD28(-)CD57(+) cells among CD4(+) T cells ) and CD4(+)/CD8(+) T-cell exhaustion (ie, the percentage of PD-1(+) cells among CD4(+)/CD8(+) T cells) decreased after ART. There were no changes in markers of CD8(+) T-cell senescence after ART and no differential changes in all markers in ART groups. Senescent CD4(+) and CD8(+) T cells may have differential roles in HIV pathogenesis.
authors.affiliation: David Geffen School of Medicine at UCLA.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Kelesidis
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Carlee
authors.initials: C
authors.lastname: Moser
authors.affiliation: University of Wisconsin School of Medicine and Public Health, Madison.
authors.forename: James H
authors.initials: JH
authors.lastname: Stein
authors.affiliation: Johns Hopkins University, Baltimore, Maryland.
authors.forename: Todd T
authors.initials: TT
authors.lastname: Brown
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Thuy Tien T
authors.initials: TT
authors.lastname: Tran
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Ribaudo
authors.affiliation: Keck School of Medicine at the University of Southern California, Los Angeles.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Dube
authors.affiliation: David Geffen School of Medicine at UCLA.
authors.forename: Otto O
authors.initials: OO
authors.lastname: Yang
authors.affiliation: David Geffen School of Medicine at UCLA.
authors.forename: Judith S
authors.initials: JS
authors.lastname: Currier
authors.affiliation: Case Western Reserve University School of Medicine University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Grace A
authors.initials: GA
authors.lastname: McComsey
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015703:Antigens, CD / Q000032:analysis; D000069446:Atazanavir Sulfate / Q000627:therapeutic use*; D000069454:Darunavir / Q000627:therapeutic use*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D011446:Prospective Studies; D000068898:Raltegravir Potassium / Q000627:therapeutic use*; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*
chemical_list: D019380:Anti-HIV Agents; D015703:Antigens, CD; D000068898:Raltegravir Potassium; D000069446:Atazanavir Sulfate; D000069454:Darunavir
keywords: antiretroviral therapy; biomarkers; human immunodeficiency virus; immune activation; inflammation