Mucosal Determinants of HIV Infection of Infants by Breast Milk

描述(由申请人提供)：非常有希望的最新观察数据显示，纯母乳喂养可以大大降低HIV6-9的产后母婴传播(MTCT)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25%，占每年2-30万儿童感染者的比例。由于持续接触牛奶中的病毒，产前抗逆转录病毒疗法(ART)获得的保护可能在出生后失去。事实上，母乳喂养导致了25%-44%的母婴传播。在出生后早期至4-6周期间，艾滋病毒的传播率极高(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，对于较晚的产后传播(6周至6个月)，在前3个月实行“纯”母乳喂养，而不是“混合”母乳喂养，可将婴儿艾滋病毒感染减少2倍。在“纯”母乳喂养(EBF)中，只喂母乳，不添加额外的液体或食物，而在“混合”喂养(MBF)中，其他食物很早就被引入。通过具体和实质性的咨询干预，实践循证医学的可能性增加了。我们建议确定喂养做法(EBF与MBF)的生物学后果，这些做法可能会合理地导致出生后艾滋病毒感染的风险。我们建议将母乳喂养对母亲乳汁和婴儿肠道的微生物学、免疫学和炎症状态的影响表征为将艾滋病毒传播给婴儿的风险的决定因素。与公共卫生相关：在每天1500例母婴传播艾滋病毒病例中，母乳传播占三分之一至一半(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(不含其他食物)可能会显著降低这些比率，同时保留母乳对肺炎、腹泻和死亡的保护作用。我们建议对这种保护的机制进行表征，以确定保护这些儿童的有效战略。

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.