HIV-specific cytotoxic T lymphocytes, HLA-A11, and chemokine-related factors may act synergistically to determine HIV resistance in CCR5 Delta 32-negative female sex workers in Chiang Rai, Northern Thailand

Understanding how highly HIV-exposed individuals remain HIV uninfected may be useful for HIV vaccine design and development of new HIV prevention stra tegies. To elucidate mechanisms associated with resistance to HIV infection , immunologic and genetic factors were examined in 14 HIV-exposed but persi stently seronegative (HEPS) female sex workers from Chiang Rai, northern Th ailand and in ethnically matched, HIV-positive (n = 9) and HIV-negative wom en (n = 9), The HERS women were identified in a study of commercial sex wor kers who had an HIV-1 incidence of 20.3 per 100 person-years. A high freque ncy of HLA-A11 was observed in HEPS women (86%) compared with northern Thai controls (56%), HIV-specific cytotoxic T lymphocyte (CTL) lytic responses were detected in cryopreserved peripheral blood mononuclear cells (PBMCs), using HLA-A-matched subtype E HIV-1 peptides in four of seven (57%) HEPS wo men, eight of eight HIV-positive women, and zero of nine HIV-negative unexp osed controls (p = 0.019 HEPS women vs. HIV-negative controls). CTL lysis l evels were low, but responses were detected to peptides from Nef, Pol, Gag, and Env, Nef responses predominated in HEPS women. Compared with controls, HEPS women tended to have higher frequencies of CCR5 promotor 59402GG and SDF-1 3'UTR 801A genotypes known to influence HIV transmission or course of disease. HEPS women also had higher levels of spontaneous RANTES productio n by PBMCs than other groups. Each of these factors could potentially contr ibute to HIV resistance. As most HEPS women had one or more of these factor s, they may prevent HIV infection synergistically by blocking HIV cell entr y, delaying its dissemination, or killing HIV-infected cells.