CCR5 Chemokine Receptor Variant in HIV-1 Mother-to-Child Transmission and Disease Progression in Children

CONTEXT.— Studies suggest that adults with the CCR5Δ32 deletion are less likely to become infected with the human immunodeficiency virus (HIV) and to develop HIV-related disease progression, but the effect of the mutation in children is not known. OBJECTIVE.— To study the effect of the CCR5 chemokine receptor mutant allele on mother-to-child transmission of HIV type 1 (HIV-1) and subsequent disease progression in infected children. DESIGN.— Multicenter, prospective study of infants born to mothers seropositive for HIV-1. SETTING.— A total of 52 medical centers participating in the French Pediatric HIV Cohort studies. PARTICIPANTS.— The CCR5Δ32 deletion was studied in 512 non-African children, born between 1983 and 1996 to HIV-1–infected mothers. Among them, 276 children were infected and 236 were not. MAIN OUTCOME MEASURES.— HIV-1 infection status and, in infected children followed up since birth, incidence of category B and C disease events and severe immunosuppression as defined in the new pediatric Centers for Disease Control and Prevention (CDC) classification, according to CCR5 genotype. RESULTS.— The 32–base pair deleted allele was detected at a frequency of 0.05. Only 1 infant, not infected by HIV-1, was homozygous for the Δ32 deletion. The 49 heterozygous children (9.6% of the total; 95% confidence interval [CI], 7.1-12.2) were equally distributed into the infected (9.8%) and uninfected (9.3%) groups. The incidence of stage C symptoms in heterozygous infected children was 9% at 36 months vs 28% in children homozygous for the normal allele (P