CCR5 CHEMOKINE RECEPTOR VARIANT IN HIV-1 MOTHER-TO-CHILD TRANSMISSIONAND DISEASE PROGRESSION IN CHILDREN

Context.-Studies suggest that adults with the CCR5 Delta 32 deletion a re less likely to become infected with the human immunodeficiency viru s (HIV) and to develop HIV-related disease progression, but the effect of the mutation in children is not known. Objective.-To study the eff ect of the CCR5 chemokine receptor mutant allele on mother-to-child tr ansmission 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. Par ticipants.-The CCR5 Delta 32 deletion was studied in 512 non-African c hildren, born between 1983 and 1996 to HIV-1-infected mothers. Among t hem, 276 children were infected and 236 were not. Main Outcome Measure s.-HIV-1 infection status and, in infected children followed up since birth, incidence of category B and C disease events and severe immunos uppression as defined in the new pediatric Centers for Disease Control and Prevention (CDC) classification, according to CCR5 genotype. Resu lts.-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 Delta 32 deletion. The 49 heterozygous children (9.6% of the total; 95% con fidence interval [CI], 7.1-12.2) were equally distributed into the inf ected (9.8%) and uninfected (9.3%) groups. The incidence of stage C sy mptoms in heterozygous infected children was 9% at 36 months vs 28% in children homozygous for the normal allele (P<.004). The proportion of children at 8 years old with no stage B or C symptoms was 49% for het erozygous children and 11% for children homozygous for the normal alle le (P<.003). The progression of severe immune deficiency (CD4 <15%, CD C stage 3) was also significantly different between the 2 groups (P<.0 01). Conclusions.-Heterozygosity for the CCR5 Delta 32 deletion does n ot protect children from infection by the maternal virus but substanti ally reduces the progression of the disease in HIV-1-infected children .