Role for HLA class II molecules in HIV-1 suppression and cellular immunityfollowing antiretroviral treatment

HIV-1-infected patients treated early with combination antiretrovirals resp ond favorably, but not all maintain viral suppression and improved HIV-spec ific Th function. To understand if genetic factors contribute to this varia tion, we prospectively evaluated over 18 months 21 early-treated patients s tratified by alleles of class II haplotypes. All seven subjects with the DR B1*13-DQB1*06 haplotype, but only 21% of other subjects, maintained virus s uppression at every posttreatment measurement. Following HIV-1 p24 antigen stimulation, PBMCs from patients with this haplotype demonstrated higher me an lymphoproliferation and IFN-gamma secretion than did cells from patients with other haplotypes. Two DRB1*13-restricted Gag epitope regions were ide ntified, a promiscuous one that bound its putative restriction element with nanomolar affinity, and another that mapped to a highly conserved region. These findings suggest that class II molecules, particularly the DRB1*13 ha plotype, have an important impact on virologic and immunologic responses. T he advantage of the haplotype may relate to selection of key HIV-1 Th1 epit opes in highly conserved regions with avid binding to class II molecules. E liciting responses to the promiscuous epitope region may be beneficial in v accine strategies.