title: Lower Viral Loads and Slower CD4+ T-Cell Count Decline in MRKAd5 HIV-1 Vaccinees Expressing Disease-Susceptible HLA-B*58:02.
abstract: HLA strongly influences human immunodeficiency virus type 1 (HIV-1) disease progression. A major contributory mechanism is via the particular HLA-presented HIV-1 epitopes that are recognized by CD8(+) T-cells. Different populations vary considerably in the HLA alleles expressed. We investigated the HLA-specific impact of the MRKAd5 HIV-1 Gag/Pol/Nef vaccine in a subset of the infected Phambili cohort in whom the disease-susceptible HLA-B*58:02 is highly prevalent.
  
  
  
  Viral loads, CD4(+) T-cell counts, and enzyme-linked immunospot assay-determined anti-HIV-1 CD8(+) T-cell responses for a subset of infected antiretroviral-naive Phambili participants, selected according to sample availability, were analyzed.
  
  
  
  Among those expressing disease-susceptible HLA-B*58:02, vaccinees had a lower chronic viral set point than placebo recipients (median, 7240 vs 122 500 copies/mL; P = .01), a 0.76 log10 lower longitudinal viremia level (P = .01), and slower progression to a CD4(+) T-cell count of <350 cells/mm(3) (P = .02). These differences were accompanied by a higher Gag-specific breadth (4.5 vs 1 responses; P = .04) and magnitude (2300 vs 70 spot-forming cells/10(6) peripheral blood mononuclear cells; P = .06) in vaccinees versus placebo recipients.
  
  
  
  In addition to the known enhancement of HIV-1 acquisition resulting from the MRKAd5 HIV-1 vaccine, these findings in a nonrandomized subset of enrollees show an HLA-specific vaccine effect on the time to CD4(+) T-cell count decline and viremia level after infection and the potential for vaccines to differentially alter disease outcome according to population HLA composition.
  
  
  
  NCT00413725, DOH-27-0207-1539.
authors.affiliation: Department of Paediatrics.
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Leitman
authors.affiliation: Nuffield Department of Medicine, University of Oxford, United Kingdom.
authors.forename: Jacob
authors.initials: J
authors.lastname: Hurst
authors.affiliation: Department of Paediatrics.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Mori
authors.affiliation: HIV-1 Vaccine Trials Network, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center.
authors.forename: James
authors.initials: J
authors.lastname: Kublin
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts HIV-1 Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal KwaZulu-Natal Research Institute for Tuberculosis and HIV-1, University of KwaZulu-Natal, Durban Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Thumbi
authors.initials: T
authors.lastname: Ndung'u
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts HIV-1 Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.affiliation: eScience Group, Microsoft Research, Redmond, Washington.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Carlson
authors.affiliation: South African Medical Research Council, Cape Town Perinatal HIV-1 Research Unit, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Glenda E
authors.initials: GE
authors.lastname: Gray
authors.affiliation: Nuffield Department of Medicine, University of Oxford, United Kingdom.
authors.forename: Philippa C
authors.initials: PC
authors.lastname: Matthews
authors.affiliation: HIV-1 Vaccine Trials Network, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center Department of Global Health, University of Washington, Seattle.
authors.forename: Nicole
authors.initials: N
authors.lastname: Frahm
authors.affiliation: Department of Paediatrics HIV-1 Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal.
authors.forename: Philip J R
authors.initials: PJ
authors.lastname: Goulder
mesh_terms: D000328:Adult; D000483:Alleles; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D015658:HIV Infections / Q000517:prevention & control* / Q000821:virology*; D015235:HLA-B Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D010919:Placebos / Q000008:administration & dosage; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D019562:Viral Load; D055815:Young Adult
chemical_list: D015235:HLA-B Antigens; C041533:HLA-B58 antigen; D010919:Placebos; D018449:SAIDS Vaccines
keywords: Gag-specific CD8+ T cells; HIV-1 vaccine; HLA class I; Phambili trial