CCR5 genotype and resistance to vertical transmission of HIV-1

A human gene has been identified that affects susceptibility to HIV-1 infec tion. The gene codes for CCR5, the coreceptor for macrophage-tropic strains of HIV-1. Individuals who are homozygous for a deleted, mutant form of the gene, Delta 32, display a high degree of natural resistance to sexual and parenteral transmission of HIV-1. To investigate whether Delta 32 plays a r ole in vertical transmission, we determined the CCR5 genotype of 552 childr en born to infected mothers in the United States and correlated the genotyp es with HIV-1 infection status. Of these children, 13% were white, 30% Lati no, and 56% African American, reflecting the ethnic makeup of infected wome n in the United States. The Delta 32 gene frequency varied among these grou ps, ranging from 0.08 in whites to 0.02 in both Latinos and African America ns. Approximately 27% of the children in each ethnic group were infected. F our children were identified as Delta 32 homozygotes, two uninfected whites (3.77%) and two uninfected Latinos (1.68%). None of the infected children displayed the Delta 32 homozygous genotype. Among Latinos and whites, the n umber of uninfected children who carried the homozygous Delta 32 mutation w as significantly greater than that predicted by the Hardy-Weinberg equilibr ium (p < .001 for Latinos, p = .044 for whites). This association was noted in Latino and white children whose mothers were either treated or untreate d with zidovudine, These data document the occurrence of the homozygous Del ta 32 genotype among children of HIV-1-infected mothers and suggest that th is mutant genotype may confer protection from mother-to-child transmission of HIV-1, They also suggest that sexual, parenteral, and vertical transmiss ion all involve processes that use CCR5 as a coreceptor for primary HIV-1 i nfection. Therefore, blocking the CCR5 receptor may provide an additional s trategy to prevent HIV-1 vertical transmission.