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Breast milk cellular HIV-specific interferon &ggr; responses are associated with protection from peripartum HIV transmission

Objective:Breast milk is a major route of infant HIV infection, yet the majority of breast-fed, HIV-exposed infants escape infection by unknown mechanisms. This study aimed to investigate the role of HIV-specific breast milk cells in preventing infant HIV infection. Design:A prospective study was designed to measure associations between maternal breast milk HIV-specific interferon-&ggr; (IFN-&ggr;) responses and infant HIV-1 detection at 1 month of age. Methods:In a Kenyan cohort of HIV-infected mothers, blood and breast milk HIV-gag IFN-&ggr; ELISpot responses were measured. Logistic regression was used to measure associations between breast milk IFN-&ggr; responses and infant HIV infection at 1 month of age. Results:IFN-&ggr; responses were detected in breast milk from 117 of 170 (69%) women. IFN-&ggr; responses were associated with breast milk viral load, levels of macrophage inflammatory protein (MIP) 1&agr;, MIP-1&bgr;, regulated upon activation, normal T-cell expressed, and secreted and stromal-cell derived factor 1 and subclinical mastitis. Univariate factors associated with infant HIV infection at 1 month postpartum included both detection and breadth of breast milk IFN-&ggr; response (P = 0.08, P = 0.04, respectively), breast milk MIP-1&bgr; detection (P = 0.05), and plasma (P = 0.004) and breast milk (P = 0.004) viral load. In multivariate analyses adjusting for breast milk viral load and MIP-1&bgr;, breast milk IFN-&ggr; responses were associated with an approximately 70% reduction in infant HIV infection [adjusted odds ratio (aOR) 0.29, 95% confidence interval (CI) 0.092–0.91], and each additional peptide pool targeted was associated with an approximately 35% reduction in infant HIV (aOR 0.65, 95% CI 0.44–0.97). Conclusion:These data show breast milk HIV-gag-specific IFN-&ggr; cellular immune responses are prevalent and may contribute to protection from early HIV transmission. More broadly, these data suggest breast milk cellular responses are potentially influential in decreasing mother-to-child transmission of viruses.