title: Influence of HLA-B57 on clinical presentation and viral control during acute HIV-1 infection.
abstract: BACKGROUND
  HLA-B57, as well as cytotoxic T-lymphocyte (CTL) responses restricted by this allele, have been strongly associated with long-term non-progressive chronic HIV-1 infection. However, their impact on viral replication during acute HIV-1 infection is not known.
  
  
  METHODS
  Clinical and immunological parameters during acute and early HIV-1 infection in individuals expressing HLA-B57 were assessed. HIV-1-specific T-cell responses were determined by peptide-specific interferon-gamma production measured using Elispot assay and flow-based intracellular cytokine quantification.
  
  
  RESULTS
  Individuals expressing HLA-B57 presented significantly less frequently with symptomatic acute HIV-1 infection (4/116, 3.4%) than expected from the frequency of chronically infected individuals expressing this allele (43/446, 9.6%; P < 0.05). During acute infection, virus-specific CD8 T-cell responses were dominated by HLA-B57-restricted responses, with significantly broader (P < 0.02) and stronger (P < 0.03) responses restricted by HLA-B57 than restricted by all other co-expressed HLA class I alleles combined. Six out of nine individuals expressing HLA-B57 controlled HIV-1 viremia in the absence of therapy at levels < 5000 copies/ml (median, 515 copies/ml) during up to 29 months following acute infection.
  
  
  CONCLUSIONS
  These data demonstrate that host genetic factors can influence the clinical manifestations of acute HIV-1 infection and provide a functional link between HLA-B57 and viral immune control.
authors.affiliation: Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Marcus
authors.initials: M
authors.lastname: Altfeld
authors.forename: Marylyn M
authors.initials: MM
authors.lastname: Addo
authors.forename: Eric S
authors.initials: ES
authors.lastname: Rosenberg
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Hecht
authors.forename: Paul K
authors.initials: PK
authors.lastname: Lee
authors.forename: Martin
authors.initials: M
authors.lastname: Vogel
authors.forename: Xu G
authors.initials: XG
authors.lastname: Yu
authors.forename: Rika
authors.initials: R
authors.lastname: Draenert
authors.forename: Mary N
authors.initials: MN
authors.lastname: Johnston
authors.forename: Daryld
authors.initials: D
authors.lastname: Strick
authors.forename: Todd M
authors.initials: TM
authors.lastname: Allen
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Feeney
authors.forename: James O
authors.initials: JO
authors.lastname: Kahn
authors.forename: Rafick P
authors.initials: RP
authors.lastname: Sekaly
authors.forename: Jay A
authors.initials: JA
authors.lastname: Levy
authors.forename: Jürgen K
authors.initials: JK
authors.lastname: Rockstroh
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Goulder
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
mesh_terms: D000208:Acute Disease; D000328:Adult; D000483:Alleles; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005805:Genes, MHC Class I / Q000276:immunology; D015658:HIV Infections / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014779:Virus Replication / Q000235:genetics / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D015235:HLA-B Antigens; C103707:HLA-B57 antigen; D016056:Immunodominant Epitopes