Session 60Poster Presentations Primary HIV/SIV Infection Session Day and Time: Tuesday 1:30 - 3:30 pm Room: Hall A
510 Influence of HLA-B57 on Clinical Presentation and Viral Control during Acute HIV-1 Infection M. Altfeld*1, M. M. Addo1, E. S. Rosenberg1, F. M. Hecht2, P. K. Lee1, M. Vogel3, R. Draenert1, X. G. Yu1, M. N. Johnston1, Todd M. Allen1, Rafick P. Sekaly4, Jay A. Levy5, Jürgen K. Rockstroh3, Philip J. R. Goulder1, Bruce D. Walker1 1Massachusetts General Hosp, Boston; 2Univ of California at San Francisco; 3Univ of Bonn, Germany; 4Inst de Recherches Cliniques de Montreal, Canada; and 5Univ of California at San Francisco
Background: HLA-B57, as well as CTL responses restricted by this allele, have been strongly associated with long-term, non-progressive HIV-1 infection. However, their impact on viral replication during acute HIV-1 infection is not understood. In this study, we assessed clinical and immunological parameters during acute and early HIV-1 infection in individuals expressing HLA-B57.
Methods: We enrolled 116 individuals with acute HIV-1 infection from different Acute Infection Cohorts in the U.S., Canada, and Germany. Clinical symptoms during acute infection were documented and the HLA class I alleles expressed in these individuals were characterized. HIV-1-specific CD8+ T-cell responses were assessed using optimal CTL epitopes described for the HLA class I alleles expressed in each individual as well as using overlapping peptides spanning the entire expressed HIV-1 clade B consensus sequence, using Elispot and ICS.
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 HLA-B57 (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 HLA class I alleles combined. Six (6) out of 9 individuals expressing HLA-B57 controlled HIV-1 viremia in the absence of therapy at levels below 5,000 copies (median 515 copies) during up to 29 months following acute infection.
Conclusions: These data indicate that HLA-B57 does not protect from acquisition of HIV-1 infection, but that individuals expressing this allele present significantly less frequently with symptomatic acute infection and high-level viremia. These data demonstrating an association between strong HIV-1-specific immune responses restricted by HLA-B57 during acute infection and low viral load indicate a crucial role of the early cellular immune response in the control of HIV-1 viremia.
