Mismatched human leukocyte antigen alleles protect against heterosexual HIV transmission

Genetic variation at the human leukocyte antigen (HLA) loci has been shown to he an important risk factor for progression to HIV disease, but its sign ificance in infection is less well understood. We have investigated its rol e in HIV transmission in a cohort of individuals at risk for heterosexual i nfection. Analysis of over 80 individuals revealed that that the degree of concordance at HLA A, B, and DR loci differs significantly between transmit ting and nontransmitting couples at risk for heterosexual HIV transmission (p < .02), suggesting that allogeneic immune responses may confer a degree of protection against HIV infection. Analysis of the frequencies of specifi c alleles at the A, B, and DR loci revealed a significantly higher frequenc y of HLA DR5 among exposed uninfected individuals, relative to population c ontrols.