Influence of HLA-B57 on clinical presentation and viral control during acute HIV-1 infection

AIDS. 2003 Dec 5;17(18):2581-91. doi: 10.1097/00002030-200312050-00005.

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Adult
  • Alleles
  • CD8-Positive T-Lymphocytes / immunology
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Genes, MHC Class I / immunology
  • HIV Infections / genetics
  • HIV Infections / immunology*
  • HIV-1 / genetics
  • HIV-1 / immunology
  • HIV-1 / physiology*
  • HLA-B Antigens / genetics
  • HLA-B Antigens / immunology*
  • Humans
  • Immunodominant Epitopes / immunology
  • Male
  • Middle Aged
  • Mutation
  • T-Lymphocytes, Cytotoxic / immunology
  • Virus Replication / genetics
  • Virus Replication / immunology*

Substances

  • Epitopes, T-Lymphocyte
  • HLA-B Antigens
  • HLA-B57 antigen
  • Immunodominant Epitopes