Effects of CCR5-δ32 and CCR2-641 alleles on disease progression of perinatally HIV-1-infected children: An international meta-analysis

John P.A. Ioannidis, Despina G. Contopoulos-Ioannidis, Philip S. Rosenberg, James J. Goedert, Anita De Rossi, Teresa Espanol, Lisa Frenkel, Marie Jeanne Mayaux, Marie Louise Newell, Savita G. Pahwa, Christine Rousseau, Gabriella Scarlatti, Shizuko Sei, Luisa Sen, Thomas R. O'Brien

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Objective: Among perinatally infected children, the effects of certain alleles of the CCR5 and CCR2 genes on the rate of disease progression remain unclear. We addressed the effects of CCR5-A32 and CCR2-641 in an international meta-analysis. Methods: Genotype data were contributed from 10 studies with 1317 HIV-1-infected children (7263 person-years of follow-up). Time-to-event analyses were performed stratified by study and racial group. Endpoints included progression to clinical AIDS, death, and death after the diagnosis of clinical AIDS. The time-dependence of the genetic effects was specifically investigated. Results: There was large heterogeneity in the observed rates of disease progression between different cohorts. For progression to clinical AIDS, both CCR5-A32 and CCR2-641 showed overall non-significant trends for protection [hazard ratios 0.84, 95% confidence interval (Cl) 0.58-1.23; and 0.87, 95% Cl 0.67-1.14, respectively]. However, analyses of survival showed statistically significant time-dependence. No deaths occurred among CCR5-A32 carriers in the first 3 years of life, whereas there was no protective effect (hazard ratio 0.95; 95% Cl 0.43-2.10) in later years (P = 0.01 for the time-dependent model). For CCR2-641, the hazard ratio for death was 0.69 (95% Cl 0.39-1.21) in the first 6 years of life and 2.56 (95% Cl 1.26-5.20) subsequent years (P < 0.01 for the time-dependent model). CCR5-Δ32 and CCR2-641 offered no clear protection after clinical AIDS had developed. Conclusion: The CCR5-A32 and CCR2-641 alelles are associated with a decreased risk of death among perinatally infected children, but only for the first years of life.

Original languageEnglish (US)
Pages (from-to)1631-1638
Number of pages8
JournalAIDS
Volume17
Issue number11
DOIs
StatePublished - Jul 25 2003
Externally publishedYes

Keywords

  • CCR2-64I
  • CCR5-Δ32
  • Death
  • Disease progression
  • HIV-1
  • Perinatal transmission

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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