Protection against human immunodeficiency virus type 1 infection in persons with repeated exposure: Evidence for T cell immunity in the absence of inherited CCR5 coreceptor defects

It has been hypothesized that protection against human immunodeficiency vir us (HIV)-1 infection may result from either acquired host immunity, inherit ance of a dysfunctional CCR5 HIV-1 coreceptor, or a low or attenuated virus inoculum, Thirty-seven HIV-1-uninfected persons engaging in repeated high- risk sexual activity with an HIV-1-infected partner were prospectively stud ied to determine the contribution of these factors in protecting against HI V-1 transmission. More than one-third (13/36) demonstrated HIV-1-specific c ytotoxicity, and this activity significantly correlated with the wild type CCR5 genotype (P = .03), Only 1 subject (3%) demonstrated the homozygous CC R5 32-bp deletion (Delta 32/Delta 32). Median plasma HIV-1 RNA levels from 18 HIV-1-infected sex partners were not statistically different from those of matched infected control patients. These results indicate that inheritan ce of the Delta 32 CCR5 mutation does not account for the majority of persi stently HIV-1-resistant cases, and the presence of cellular immunity in the se persons suggests either undetected infection or protective immunity.