Maternal Humoral Immune Correlates of Peripartum Transmission of Clade C HIV-1 in the Setting of Peripartum Antiretrovirals.

Despite widespread use of antiretrovirals (ARV), more than 150,000 pediatric HIV-1 infections continue to occur annually. Supplemental strategies are necessary to eliminate pediatric HIV infections. We previously reported that maternal HIV envelope-specific anti-V3 IgG, CD4 binding site-directed antibodies, and tier 1 virus neutralization predicted reduced risk of mother-to-child transmission of HIV-1 (MTCT) in the pre-ARV era US-based Women and Infants Transmission Study (WITS) cohort. As the majority of ongoing pediatric HIV infections occur in sub-Saharan Africa, we sought to determine if the same maternal humoral immune correlates predicted MTCT in a subset of the Malawian Breastfeeding, Antiretrovirals, and Nutrition (BAN) cohort of HIV-infected mothers (n=88, 45 transmitting and 43 non-transmitting). Women and infants received ARV at delivery, thus the majority of MTCT was in utero (91%). In a multivariable logistic regression model, neither maternal anti-V3 IgG nor clade C tier 1 virus neutralization were associated with MTCT. Unexpectedly, maternal CD4 binding site antibodies and anti-V1V2 IgG were associated with increased MTCT, independent of maternal viral load. Neither infant Env-specific IgG levels nor maternal IgG transplacental transfer efficiency were associated with transmission. Distinct humoral immune correlates of MTCT in the BAN and WITS studies could be due to differences between transmission mode, virus clade, or maternal antiretroviral use. The association between specific maternal antibody responses and in utero transmission, distinct from potentially protective maternal antibodies in the WITS cohort, underlines the importance of investigating additional cohorts with well-defined transmission modes to understand the role of antibodies during HIV-1 MTCT.