Insights into the role of host genetic and T-cell factors in resistance to HIV transmission from studies of highly HIV-exposed Thais.

Studies of resistance to HIV-1 transmission are likely to be valuable for the design of vaccines and other efforts to prevent HIV. Here, we review the T-cell and genetic factors associated with resistance to HIV-1 transmission in studies of highly exposed but persistently seronegative (HEPS) women from northern Thailand. Women were enrolled in two sex-worker studies and in a discordant couple study. We performed Cr51 cytotoxic T lymphocyte (CTL), interferon-gamma (IFN-gamma) ELISPOT, and proliferation assays as well as genetic studies, including HLA-class I typing. CTL and ELISPOT studies showed a skewing of T-cell responses to conserved HIV-1 proteins in HEPS, but not in HIV-1-seropositive women. T-cell responses were extremely long-lived in some HEPS women. In the two sex-worker studies, HLA-A11 was associated with resistance to HIV-1 transmission. These data provide promise for the ability of CTL to control HIV and emphasize the importance of developing HIV vaccines that stimulate strong, long-lasting Tcell responses.