Associations of chemokine receptor polymorphisms with HIV-1 mother-to-child transmission in sub-Saharan Africa: Possible modulation of genetic effects by antiretrovirals

HIV-1 mother-to-child transmission (MTCT) remains an important route of infection in sub-Saharan Africa. Genetic variants in CCR5 promoter, CCR2, CX ₃CRX, and Stromal cell-derived factor-1 (SDF-1) genes were determined in 980 infants from sub-Saharan Africa using real-time polymerase chain reaction to determine association with MTCT. In antiretroviral-naive mother-infant pairs (n = 637), CCRS promoter polymorphisms at positions 59029: A allele vs. G/G [odds ratio (OR): 1.61, 95% confidence interval (CI): 1.04 to 2.48; P = 0.032] and 59356: Ta allele vs. C/C (OR: 0.63, 95% CI: 0.41 to 0.96; P = 0.033) and CCR2-180: G allele vs. A/A (OR: 3.32,95% CI: 1.13 to 9.73; P = 0.029) were associated with risk of MTCT. Treatment of HIV-1-infected mothers and infants with single-dose nevirapine or perinatal zidovudine altered but did not eliminate the association of genetic variants with MTCT. CCR5 promoter, CCR2, and CX ₃CR1 polymorphisms were associated with risk of MTCT likely through their role as an HIV-1 coreceptor or by modulating the early immune response. Host genetics may continue to alter MTCTwhen short-course interventions that only partially suppress virus are used. These findings will need to be confirmed in validation cohorts with a large number of infected infants.