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（MTCT）的hiv -9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%，占每年感染儿童的2-30万。产前抗逆转录病毒治疗（ART）所提供的保护可能在产后由于持续接触母乳中的病毒而丧失。事实上，母乳喂养导致25-44%的母婴传播。在出生后至4-6周的早期阶段，艾滋病毒传播率极高（每周0.7-1%）。最近预防MTCT的临床试验有些令人失望。然而，对于产后晚期传播（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，可使婴儿艾滋病毒感染减少50至20倍。在“纯”母乳喂养（EBF）中，只给予母乳，不给予额外的液体或食物，而在“混合”喂养（MBF）中，其他食物在早期就被引入。实施EBF的可能性随着具体和实质性的咨询干预而增加。我们建议确定喂养方式的生物学后果（EBF vs. MBF），这可能是导致出生后HIV感染风险的合理因素。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定性为艾滋病毒传播给婴儿的决定因素。公共卫生相关性：母乳传播占每天1500例艾滋病毒母婴传播病例（每分钟1例）的三分之一至一半。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。我们建议描述这种保护的机制，以确定保护这些儿童的有效策略。

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.