Breast milk cellular HIV-specific interferon γ 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-gamma (IFN-gamma) 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-gagIFN-gamma ELISpot responses were measured. Logistic regression was used to measure associations between breast milk IFN-gamma responses and infant HIV infection at 1 month of age. Results: IFN-gamma responses were detected in breast milk from 117 of 170 (69%) women. IFN-gamma responses were associated with breast milk viral load, levels of macrophage inflammatory protein (MIP) 1 alpha, MIP-1 beta, 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-gamma response (P=0.08, P=0.04, respectively), breast milk MIP-1 beta 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 beta, breast milk IFN-gamma responses were associated with an approximately 70% reduction in infant HIV infection [adjusted odds ratio (aOR) 0.29, 95% confidence interval (Cl) 0.092-0.91], and each additional peptide pool targeted was associated with an approximately 35% reduction in infant HIV (aOR 0.65, 95% Cl 0.44-0.97). Conclusion: These data show breast milk HIV-gag-specific IFN-gamma 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. (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins