HLA B*5701 is highly associated with restriction of virus replication in a subgroup of HIV-infected long term nonprogressors

A unique cohort of HIV-1-infected long term nonprogressors (LTNP) with normal CD4 + T cell counts and P < 0.001]. Antigen-specific CD8 + T cells were enumerated by flow cytometric detection of intracellular IFN-γ in response to HIV antigens and HLA B*57- gag tetramer staining. No quantitative differences in the total HIV-specific CD8 + T cell responses were observed between B*57 + LTNP and five B*57 + progressors ( P = 0.4). Although similar frequencies of peptide specific CD8 + T cells were also found, the gag -specific CD8 + T cell response in the LTNP group was highly focused on peptides previously shown to be B*57-restricted. These findings indicate that, within this phenotypically and genotypically distinct cohort, a host immune factor is highly associated with restriction of virus replication and nonprogressive disease. They also strongly suggest a mechanism of virus specific immunity that directly operates through the B*5701 molecule. Further characterization of qualitative differences in the virus-specific responses that distinguish HLA B*57 + LTNP from progressors may ultimately define mechanisms of effective immune mediated restriction of virus replication.