Very promising recent observational data reveal that exclusive breastfeeding can substantially reduce the rate of postnatal maternal to child transmission (MTCT) of HIV6-9. The incidence of MTCTA is H 25% among untreated HIV-infected women in Sub-Saharan Africa, accounting for >2-300,000 children infected/year. Protection achieved with prenatal antiretroviral therapy (ART) may be lost in the post-natal period with persistent exposure to the virus in milk. Indeed, breastfeeding causes 25-44% of MTCT. Rates of HIV transmission are extremely high (0.7-1% per week) in the early postnatal period from birth to 4-6 weeks. Recent clinical trials to prevent MTCT are somewhat disappointing. However, for late postnatal transmission (6 weeks to e 6 months), practicing """"""""exclusive"""""""" rather than """"""""mixed"""""""" breastfeeding in the first 3 months is associated with >2 fold reduction in infant HIV infection. In """"""""exclusive"""""""" breastfeeding (EBF), breast milk alone is given with no additional fluids or foods, whereas with """"""""mixed"""""""" feeding (MBF), other foods are introduced early. The probability of practicing EBF has increased with specific and substantial counseling interventions. We propose to identify the biological consequences of feeding practices (EBF vs. MBF) that may plausibly contribute to the risk of postnatal HIV infection. We propose to characterize the impact of breastfeeding practices on the microbiologic, immunologic, and inflammatory status of both the mother's milk and infant intestine as determinants of risk for transmission of HIV to infants.
Breast milk transmission accounts for a third to a half of the 1500 cases of maternal-to-child-transmission of HIV every day (1 per minute). Interventions to limit these infections have been few. New data suggest that exclusive breastfeeding (no other foods), compared with mixed feeding, may significantly decrease these rates while retaining the protective effects of breast milk against pneumonia, diarrhea, and death. We propose to characterize the mechanisms of this protection to define effect strategies to protect these children.
|McFarland, Elizabeth J; Powell, Tina M; Onyango-Makumbi, Carolyne et al. (2017) Ontogeny of CD4+ T Lymphocytes With Phenotypic Susceptibility to HIV-1 During Exclusive and Nonexclusive Breastfeeding in HIV-1-Exposed Ugandan Infants. J Infect Dis 215:368-377|
|Shen, Ruizhong; Achenbach, Jenna; Shen, Yue et al. (2015) Mother-to-Child HIV-1 Transmission Events Are Differentially Impacted by Breast Milk and Its Components from HIV-1-Infected Women. PLoS One 10:e0145150|
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|Pujanauski, Lindsey M; Janoff, Edward N; McCarter, Martin D et al. (2013) Mouse marginal zone B cells harbor specificities similar to human broadly neutralizing HIV antibodies. Proc Natl Acad Sci U S A 110:1422-7|
|Frank, Daniel N; Manigart, Olivier; Leroy, Valeriane et al. (2012) Altered vaginal microbiota are associated with perinatal mother-to-child transmission of HIV in African women from Burkina Faso. J Acquir Immune Defic Syndr 60:299-306|
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|Shiflett, Michael W; Balleine, Bernard W (2011) Contributions of ERK signaling in the striatum to instrumental learning and performance. Behav Brain Res 218:240-7|
|Frank, Daniel N; Zhu, Wei; Sartor, R Balfour et al. (2011) Investigating the biological and clinical significance of human dysbioses. Trends Microbiol 19:427-34|
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