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JAIDS Journal of Acquired Immune Deficiency Syndromes:

Rapid Communication CCR5 Genotype and Resistance to Vertical Transmission of HIV-1.

Philpott, Sean; Burger, Harold; Charbonneau, Tina; Grimson, Roger; Vermund, Sten H.; Visosky, Aloise; Nachman, Sharon; Kovacs, Andrea; Tropper, Pamela; Frey, Henry; Weiser, Barbara

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Summary: A human gene has been identified that affects susceptibility to HIV-1 infection. 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 role in vertical transmission, we determined the CCR5 genotype of 552 children born to infected mothers in the United States and correlated the genotypes with HIV-1 infection status. Of these children, 13% were white, 30% Latino, and 56% African American, reflecting the ethnic makeup of infected women in the United States. The [DELTA]32 gene frequency varied among these groups, ranging from 0.08 in whites to 0.02 in both Latinos and African Americans. Approximately 27% of the children in each ethnic group were infected. Four 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 number of uninfected children who carried the homozygous [DELTA]32 mutation was significantly greater than that predicted by the Hardy-Weinberg equilibrium (p < .001 for Latinos,/= .044 for whites). This association was noted in Latino and white children whose mothers were either treated or untreated with zidovudine. These data document the occurrence of the homozygous [DELTA]32 genotype among children of HIV-1-infected mothers and suggest that this mutant genotype may confer protection from mother-to-child transmission of HIV-1. They also suggest that sexual, parenteral, and vertical transmission all involve processes that use CCR5 as a coreceptor for primary HIV-1 infection. Therefore, blocking the CCR5 receptor may provide an additional strategy to prevent HIV-1 vertical transmission.

(C) 1999 Lippincott Williams & Wilkins, Inc.


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