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

2003; Lippincott Williams & Wilkins; Volume: 17; Issue: 18 Linguagem: Inglês

10.1097/00002030-200312050-00005

1473-5571

Marcus Altfeld, Marylyn M. Addo, Eric Rosenberg, Frederick Hecht, Paul K. Lee, Martin Vogel, Xu G. Yu, Rika Draenert, Mary N. Johnston, Daryld Strick, Todd M. Allen, Margaret E. Feeney, James O. Kahn, Rafick‐Pierre Sékaly, Jay A. Levy, Jürgen K. Rockstroh, Philip JR Goulder, Bruce D. Walker,

Cytomegalovirus and herpesvirus research

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.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.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.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.