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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.

Original publication

DOI

10.1097/01.aids.0000096870.36052.b6

Type

Journal article

Journal

AIDS

Publication Date

05/12/2003

Volume

17

Pages

2581 - 2591

Keywords

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