Mucosal Determinants of HIV Infection of Infants by Breast Milk

描述（由申请人提供）：最近非常有希望的观察数据显示，纯母乳喂养可以大大降低产后母婴传播艾滋病毒（6 -9）的比率。在撒哈拉以南非洲未经治疗的艾滋病毒感染妇女中，MTCTA的发病率为H 25%，每年有2- 30万儿童感染。产前抗逆转录病毒治疗（ART）所获得的保护可能会在出生后持续暴露于牛奶中的病毒中失去。事实上，母乳喂养导致25-44%的母婴传播。从出生到4-6周的产后早期艾滋病毒传播率极高（每周0.7-1%）。最近预防母婴传播的临床试验有些令人失望。然而，对于晚期产后传播（6周至6个月），在前3个月内实行“纯母乳喂养”而不是“混合母乳喂养”与婴儿艾滋病毒感染减少2倍以上有关。在“纯母乳喂养”（EBF）中，只提供母乳，不提供额外的液体或食物，而在“混合”喂养（MBF）中，早期引入其他食物。实践EBF的可能性增加了具体和实质性的咨询干预。我们建议确定喂养方式（EBF与MBF）的生物学后果，这可能会导致产后HIV感染的风险。我们建议将母乳喂养对母乳和婴儿肠道的微生物学、免疫学和炎症状态的影响作为HIV传播给婴儿风险的决定因素。公共卫生相关性：母乳传播占每天1 500例母婴传播艾滋病毒病例的三分之一至一半（每分钟1例）。限制这些感染的干预措施很少。新的数据表明，与混合喂养相比，纯母乳喂养（没有其他食物）可能会显着降低这些比率，同时保留母乳对肺炎，腹泻和死亡的保护作用。我们建议描述这种保护的机制，以确定有效的策略来保护这些儿童。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: 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.