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Subclinical Mastitis, Cell-Associated HIV-1 Shedding in Breast Milk, and Breast-Feeding Transmission of HIV-1

Background:Mastitis has been identified as a risk factor for mother-to-child transmission (MTCT) of HIV-1 through breast-feeding. It is unclear whether this association is mediated by increased cell-free virus (CFV) versus cell-associated virus (CAV) HIV shedding in breast milk. Methods:We examined the risk of MTCT associated with subclinical mastitis and the relation between mastitis and CFV or CAV shedding in breast milk. Fifty-nine women who transmitted HIV through breast-feeding (cases) were individually matched to 59 nontransmitting controls nested in a cohort from Tanzania. For each case, we selected a milk specimen obtained before the infant's first positive test to quantify sodium (Na) and potassium (K) and measure CFV and CAV concentrations. Controls were matched on the child's age at the time of sample collection. Results:Women with a breast milk Na/K ratio suggestive of mastitis (>1.0) had an 11-fold greater odds of transmission (95% confidence interval [CI]: 1.2 to 98.1), compared to women with a Na/K ≤0.6, after adjusting for maternal CD4 cell count and vitamin A supplementation. Although mastitis was positively related to both CFV and CAV shedding in breast milk, only the association with the latter was strong and statistically significant. Conclusion:Increased cell-associated HIV-1 shedding in breast milk could mediate the association between mastitis and MTCT.