CC Chemokine Receptor 5 Genotype and Susceptibility to Transmission of Human Immunodeficiency Virus Type 1 in Women

The human gene for CC chemokine receptor 5, a coreceptor for human immunodeficiency virus type 1 (HIV-1), affects susceptibility to infection. Most studies of predominantly male cohorts found that individuals carrying a homozygous deleted form of the gene, Delta 32, were protected against transmission, but protection did not extend to Delta 32 heterozygotes. The role played by this mutation in HIV-1 transmission to women was studied in 2605 participants in the Women's Interagency HIV Study. The Delta 32 gene frequency was 0.026 for HIV-1-seropositive women and 0.040 for HIV-1-seronegative women, and statistical analyses showed that Delta 32 heterozygotes were significantly less likely to be infected (odds ratio, 0.63 [95% confidence interval, 0.44-0.90]). The CCR5 Delta 32 heterozygous genotype may confer partial protection against HIV-1 infection in women. Because Delta 32 is rare in Africans and Asians, it seems plausible that differential genetic susceptibility, in addition to social and behavioral factors, may contribute to the rapid heterosexual spread of HIV-1 in Africa and Asia.