Background:  Interleukin-10 (IL-10) -secreting T cells from HIV-1-infected pregnant women have been found to inhibit HIV-1 replication and this effect is increased in women receiving antiretrovirals. However, other findings suggest that an increase in IL-10-producing CD8⁺ cells play a detrimental role and are associated with HIV-1 immune dysfunction. In this study, we examined the association of IL-10 genetic variants linked to higher IL-10 expression on HIV-1 mother-to-child transmission (MTCT).

Methods:  IL-10-1082-G/A, -819-C/T, and -592-C/A variants were detected by real-time polymerase chain reaction in 980 children born to antiretroviral (ARV) naïve HIV-1-infected mothers from Malawi (n = 322) and South Africa (n = 300); and to ARV-exposed mothers from Uganda (HIVNET-012, n = 358) where intrapartum and neonatal single-dose nevirapine (NVP) was compared with intrapartum zidovudine (ZDV) plus 7 days after birth for preventing MTCT. The c² test and logistic regression were used to evaluate the association of IL-10 polymorphisms with the risk of HIV-1 MTCT.

Results:  Overall, 21% of infants were HIV-1-infected (ARV-naïve:  145 of 637 [22.7%], NVP-exposed:  18 of 171 [10.5%], ZDV-exposed:  46 of 169 [27.2%]). IL-10 variants did not alter MTCT for ARV-naïve mother-infant pairs, either for early MTCT (within 6 weeks of birth) or through breastfeeding (after 6 weeks of birth). Presence of IL-10-1082-G/G or G/A variants (linked with higher IL-10 expression) had a modest, non-significant association with overall MTCT in NVP-exposed infants:  G/G vs A/A (OR = 0.31, 95%CI 0.04 to 2.53, P = 0.27); G/A vs A/A (OR = 0.60, 95%CI 0.22 to 1.68, P = 0.33). However, IL-10-1082-G/G or G/A genotypes were associated with increased MTCT in ZDV-exposed infants:  G/G vs A/A (OR = 3.22, 95%CI 1.09 to 9.48, P = 0.034); G/A vs A/A (OR = 3.24, 95%CI 1.46 to 7.18, P = 0.004). These findings remained after adjusting for mother’s CD4⁺ count, and log HIV-1 RNA. IL-10 haplotypes for -1082, -819, and -592 variants showed a modest, but non-statistical significant association with overall MTCT: GCC vs ATA for NVP-exposed (OR = 0.20, 95%CI 0.02 to 1.80, P = 0.15), and ZDV-exposed mother-infant pairs (OR = 2.74, 95%CI 0.75 to 10.04, P = 0.13).  

Conclusions:  Presence of IL-10-1082-G/G or G/A genotype was associated with higher MTCT in ZDV-exposed infants. These findings suggest that in the presence of ZDV administered shortly before delivery the immunosuppressive effects of IL-10 appear to dominate over its HIV-1 inhibitory effects leading to an association with increased MTCT. Validation cohort studies are needed to confirm these findings.