Polymorphisms in the CCR5 promoter region influence disease progression in perinatally Human Immunodeficiency Virus type 1-infected children

Abstract

The effect of CC-chemokine receptor 5 (CCR5) promoter polymorphisms on the natural history of human immunodeficiency virus (HIV) disease was studied in 73 HIV-1-infected children. The CCR559338-59537promoter haplotype, CCR5-59029A/G polymorphism, and CCR5Δ32 and CCR2-64I alterations were investigated. After exclusion of carriers of CCR5Δ32 or CCR2-641, Kaplan-Meier analysis disclosed that children with the P1/P159353C,59356C,59402Agenotype progressed faster to disease than did children with other haplotypes (P = .016). When CCR2-64I carriers were included, this effect had borderline significance (P = .065) and was lost when CCR5Δ32 carriers were also considered (P = .387). The P1/P1 effect was strongest early after infection, when progression to disease was mainly associated with CCR5 coreceptor-using viruses. These results indicate that the P1/P1 genotype is predictive of rapid progression in HIV-1-infected children lacking CCR5Δ32 or CCR5-64I alleles. The observation of a linkage disequilibrium between P1 and 59029A might explain the previously reported association between 59029A homozygosity and rapid disease progression.