title: CCR5 chemokine receptor variant in HIV-1 mother-to-child transmission and disease progression in children. French Pediatric HIV Infection Study Group.
abstract: BACKGROUND
  Studies suggest that adults with the CCR5delta32 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.
  
  
  METHODS
  Multicenter, prospective study of infants born to mothers seropositive for HIV-1.
  
  
  METHODS
  A total of 52 medical centers participating in the French Pediatric HIV Cohort studies.
  
  
  METHODS
  The CCR5delta32 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.
  
  
  METHODS
  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 delta32 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<.004). The proportion of children at 8 years old with no stage B or C symptoms was 49% for heterozygous children and 11% for children homozygous for the normal allele (P<.003). The progression of severe immune deficiency (CD4 <15%, CDC stage 3) was also significantly different between the 2 groups (P<.001).
  
  
  CONCLUSIONS
  Heterozygosity for the CCR5delta32 deletion does not protect children from infection by the maternal virus but substantially reduces the progression of the disease in HIV-1-infected children.
authors.affiliation: Laboratory of Hormonology and Molecular Biology, the Institut National de la Santé et de la Recherche Médicale, Unite 292, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Misrahi
authors.forename: J P
authors.initials: JP
authors.lastname: Teglas
authors.forename: N
authors.initials: N
authors.lastname: N'Go
authors.forename: M
authors.initials: M
authors.lastname: Burgard
authors.forename: M J
authors.initials: MJ
authors.lastname: Mayaux
authors.forename: C
authors.initials: C
authors.lastname: Rouzioux
authors.forename: J F
authors.initials: JF
authors.lastname: Delfraissy
authors.forename: S
authors.initials: S
authors.lastname: Blanche
mesh_terms: D000483:Alleles; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000032:analysis; D018450:Disease Progression; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000151:congenital* / Q000235:genetics* / Q000276:immunology / Q000635:transmission; D015497:HIV-1; D006579:Heterozygote; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D009154:Mutation; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology; D011446:Prospective Studies; D019713:Receptors, CCR5 / Q000235:genetics*; D012720:Severity of Illness Index
chemical_list: D019713:Receptors, CCR5; D004247:DNA