HIV TYPE-1 RESISTANCE IN KENYAN SEX WORKERS IS NOT ASSOCIATED WITH ALTERED CELLULAR-SUSCEPTIBILITY TO HIV TYPE-1 INFECTION OR ENHANCED BETA-CHEMOKINE PRODUCTION

A small group of women (n = 80) within the Nairobi-based Pumwani Sex W orkers Cohort demonstrates epidemiologic resistance to HIV-1 infection . Chemokine receptor polymorphisms and beta-chemokine overproduction h ave been among the mechanisms suggested to be responsible for resistan ce to HIV-1 infection, This study attempts to determine if any of thos e mechanisms are protecting the HIV-1-resistant women. Genetic analysi s of CCR5 and CCR3 from the resistant women demonstrated no polymorphi sms associated with resistance. Expression levels of CCR5 among the re sistant women were shown to be equivalent to that found in low-risk se ronegative (negative) controls, while CXCR4 expression was greater amo ng some of the resistant women. In vitro infection experiments showed that phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from resistant women mere as susceptible to infection to T cell- and macrophage-tropic North American and Kenyan HIV-1 isolate s as were the PBMCs from negative controls, No significant difference in circulating plasma levels of MIP-1 alpha and MIP-1 beta were found between the resistant women and negative or HIV-1-infected controls. I n vitro cultures of media and PHA-stimulated PBMCs indicated that the resistant women produced significantly less MIP-1 alpha and MIP-1 beta than did negative controls and no significant difference in RANTES le vels were observed. In contrast to studies in Caucasian cohorts, these data indicate that CCR5 polymorphisms, altered CCR5 and CXCR4 express ion levels, cellular resistance to in vitro HIV-1 infection, and incre ased levels of beta-chemokine production do not account for the resist ance to HIV-1 infection observed among the women of the Pumwani Sex Wo rkers Cohort.