860 Effect of CCR5-delta32 and CCR2-64I on the Risk of Perinatal HIV-1 Transmission: A Meta-analysis D.G. Contopoulos-Ioannidis*1, T. R. O'Brien2, J. J. Goedert2, P. S. Rosenberg2, J. P. Ioannidis1 1Univ Ioannina Med Sch, Greece and 2Natl Cancer Inst, NIH, Rockville, MD
Background: Several studies have investigated whether heterozygosity for a 32-basepair deletion in the C-C chemokine receptor 5 gene (CCR5-32bp del) affects susceptibility to perinatal HIV-1 infection, but results have been inconclusive. The effects of another polymorphism, the 64I allele of the C-C chemokine receptor 2 gene (CCR2-64I) are also controversial.
Methods: We performed a meta-analysis including data from 11 studies of HIV-1 perinatally exposed children who were genotyped for the CCR5-32bp del polymorphism. Available data were also examined for the CCR2-64I polymorphism. Data synthesis used fixed effects (Mantel-Haenszel) and random effects (DerSimonian and Laird) modeling.
Results: The crude overall HIV-1 infection rate (by simple pooling of the data across studies) was 1/5 (20%) in CCR5-32bp del homozygotes, 131/335 (39%) in CCR5-32bp del heterozygotes, and 1,408/3,526 (40%) in wild-type CCR5 children. Compared to wild-type CCR5 homozygotes, the random effects risk ratio for CCR5-32bp del heterozygotes was 1.04 (95% confidence interval [CI], 0.92-1.17) among all children (n = 3,861) and 1.03 (95% CI, 0.90-1.07) among those of European descent (n = 2,890) without any significant between-study heterogeneity. Odds ratio estimates were qualitatively similar. Results were also similar when adjusted for the available data on the CCR2-64I polymorphism (n = 1,542). The risk ratio for CCR2-64I homozygotes and heterozygotes vs wild-type CCR2 homozygotes was 0.93 (95% CI, 0.76-1.14) without any significant between-study heterogeneity.
Conclusions: The meta-analysis shows conclusively that the risk of HIV-1 perinatal transmission is unlikely to be altered by heterozygosity for CCR5-32bp del or by the presence of the CCR2-64I allele in the infant.
