Background:  Interleukin-4 (IL-4) has been shown to increase expression of CXCR4 and decrease expression of CCR5, and the IL4-589-C/T promoter polymorphism, associated with higher expression of IL-4, has been reported to provide protection in adults against HIV-1 disease progression by decreasing HIV-1 plasma RNA. We hypothesized that decreased expression of CCR5 (common HIV-1 co-receptor involved in transmission of virus) due to presence of IL4-589-T allele would reduce mother-to-child transmission (MTCT) of HIV-1.

Methods:  IL4-589-C/T polymorphisms were detected by real-time polymerase chain reaction (PCR) in 980 children born to ART-naïve HIV-1-infected mothers from Malawi (n = 322) and South Africa (n = 300); both cohorts involved in vitamin A intervention trials to reduce MTCT of HIV-1; and from Uganda (HIVNET-012, n = 358) where intrapartum and neonatal single-dose nevirapine (NVP) was compared with zidovudine (ZDV) for preventing MTCT. Data were assessed by Cochran-Mantel-Haenszel test and logistic regression analyses.

Results:  Overall, 210 (21%) of 980 children were HIV-1-infected (20% in the Malawi cohort, 25% in the South Africa cohort, and 20% in the Uganda cohort). The percentages of HIV-1-infected infants were 21%, 21%, and 22% for the IL-4-589-C/C, -C/T and -T/T genotypes, respectively (p = 0.83) and 21% infants each with T allele or C/C homozygotes were infected (p = 0.92). In logistic regression models, odds ratios for the association of HIV infection were not significant when adjusted for the study (OR = 1.04, 95%CI 0.52 to 2.05, p = 0.92), maternal CD4⁺ cell count (OR = 1.30, 95%CI 0.61 to 2.74, p = 0.50), HIV-1 RNA level (OR = 0.83, 95%CI 0.39 to 1.77, p = 0.63) or both maternal CD4⁺ cell count and HIV-1 RNA level (OR = 1.02, 95%CI 0.45 to 2.30, p = .97). Survival of the children did not vary by the presence of IL4-589 genotypes and there was no significant evidence that the association between IL4 polymorphism and HIV-1 infection varied between studies (p >0.2 in all models)

Conclusions:  The presence of IL4-589-T allele failed to affect the risk of MTCT of HIV-1 infection or survival in African infants. The studies of the effects of IL4-589-C/T polymorphism on IL4 expression and function in placental tissue with/without HIV infection are required to understand the differential regulation of CXCR4 and CCR5 expression at the maternal-fetal interface.