Effect of vitamin supplements on HIV shedding in breast milk.

BACKGROUND: Supplementation in lactating HIV-1-infected women with preformed vitamin A and ß-carotene (VA/BC) increases the risk of mother-to-child transmission of HIV through breastfeeding. Identifying a biological mechanism to explain this unexpected finding would lend support to a causal effect. OBJECTIVE: The aim of the study was to evaluate the effect of VA/BC or multivitamin (B complex, vitamin C, and vitamin E) supplementation of HIV-infected women on HIV shedding in breast milk during the first 2 y postpartum. DESIGN: We quantified viral (cell-free) and proviral (cell-associated) HIV loads in breast-milk samples collected ≤15 d after delivery and every 3 mo thereafter from 594 Tanzanian HIV-1-infected women who participated in a randomized trial. Women received 1 of the following 4 daily oral regimens in a 2 × 2 factorial fashion during pregnancy and throughout the first 2 y postpartum: multivitamin, VA/BC, multivitamin including VA/BC, or placebo. RESULTS: The proportion of breast-milk samples with detectable viral load was significantly higher in women who received VA/BC (51.3%) than in women who were not assigned to VA/BC (44.8%; P = 0.02). The effect was apparent ≥6 mo postpartum (relative risk: 1.34; 95% CI: 1.04, 1.73). No associations with proviral load were observed. The multivitamin had no effects. In observational analyses, ß-carotene but not retinol breast-milk concentrations were significantly associated with an increased viral load in milk. CONCLUSIONS: VA/BC supplementation in lactating women increases the HIV load in breast milk. This finding contributes to explaining the adverse effect of VA/BC on mother-to-child transmission. ß-Carotene appears to have an effect on breast-milk viral load, independent of preformed vitamin A. This trial was registered at clinicaltrials.gov as NCT00197756.

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

Transmission of cell-free and cell-associated HIV-1 through breast-feeding.

BACKGROUND: Transmission through breast-feeding is an important cause of infant HIV-1 infections in developing countries; however, its mechanism remains largely unknown. We have explored the association between cell-free virus (CFV) and cell-associated virus (CAV) levels in breast milk (BM), as reflected by viral RNA and proviral DNA, respectively, and the risk of infant HIV-1 infection after 6 weeks postpartum. METHODS: Sixty-one HIV-positive mothers who transmitted HIV-1 by BM were matched to 61 HIV-positive nontransmitting mothers based on their infant's age at sample collection. CFV and CAV were quantified in a single milk specimen per mother preceding the infant's first HIV-positive result. RESULTS: After adjusting for maternal CD4 cell counts and disease stage, each 10-fold increase in CFV or CAV load was associated with an almost 3-fold increase in BM transmission. Whereas CAV load was predictive of transmission before and after 9 months postpartum, CFV was a significant predictor of transmission occurring only after 9 months. Phylogenetic analyses of the C2 to C5 env region showed that 85% of infants (11 of 13 infants) harboring viruses that clustered with CFV in their mother's milk were infected after 9 months postpartum. CONCLUSION: A reduction in milk CAV and CFV loads might significantly decrease HIV-1 transmission by breast-feeding.