Effects of protein-calorie supplementation on HIV disease in breastfeeding women

描述（由申请人提供）：在世界上艾滋病毒流行的资源贫乏地区，特别是撒哈拉以南非洲国家，营养在艾滋病毒疾病中起着关键作用。营养会影响感染艾滋病毒的妇女和儿童的健康，并可能影响母婴通过母乳传播艾滋病毒的风险。营养影响结核病的风险和结核病的严重程度。现有的研究侧重于微量营养素在艾滋病毒疾病结局中的作用，但尚未解决蛋白质卡路里补充剂（PCS）在高危艾滋病毒疾病患者亚群中的作用，特别是；正在母乳喂养或患有活动性结核病的感染艾滋病毒的妇女。我们的假设是，给予文化上可接受的PCS是一种实用、可持续和有效的策略：1)降低母乳喂养妇女血浆和母乳中的艾滋病毒载量，增强母乳中的被动转移免疫介质，改善妇女及其母乳喂养婴儿的艾滋病毒结局；2)降低艾滋病毒载量，增强结核病特异性T细胞免疫，改善艾滋病毒和活动性结核病妇女的结局。我们的两个具体目标是证明这些策略在随机临床试验中是有效的。利用达特茅斯学院与坦桑尼亚Muhimbili卫生与联合科学大学之间的8年DarDar合作，我们将在达累斯萨拉姆感染艾滋病毒的妇女中开展3项营养研究。研究A将招募160名母乳喂养（BF）或患有活动性结核病的艾滋病毒阳性和艾滋病毒阳性妇女进行饮食访谈和焦点小组，以量化现有的营养缺乏症，并定义文化上可接受的PCS。研究B（118名艾滋病毒阳性和60名艾滋病毒-母乳喂养的妇女）和C（118名艾滋病毒阳性和60名艾滋病毒-活动性结核病妇女）是随机对照试验，将比较6个月PCS +微量营养素补充剂（MNS）与单独MNS对总体疾病结局的影响，以及艾滋病毒疾病的特定替代标记物、母乳中的特定免疫因子和针对结核病的特定T细胞反应。这些研究的结果预计将对营养脆弱的艾滋病毒亚群的政策产生重大影响。

DESCRIPTION (provided by applicant): In resource poor regions of the world where HIV is endemic, especially countries in sub-Saharan Africa, nutrition plays a critical role in HIV disease. Nutrition affects the health of HIV-infected women and children, and may influence the risk of mother to infant transmission of HIV through breast milk. Nutrition influences the risk of tuberculosis (TB) and TB disease severity. Existing research has focused on the role of micronutrients in HIV disease outcomes but has not addressed the role of protein calorie supplementation (PCS) in subpopulations of patients with HIV disease at high risk, specifically; HIV-infected women who are either breast feeding or have active TB. Our hypotheses are that administration of a culturally acceptable PCS is a practical, sustainable and effective strategy to: 1) decrease HIV viral load in plasma and breast milk of breast feeding women, enhance passively transferred immune mediators in breast milk, and improve HIV outcomes in women and their breast-fed infants and, 2) decrease HIV viral load, enhance TB-specific T cell immunity, and improve outcomes in women with HIV and active TB. Our two specific aims are to show that these strategies are effective in randomized clinical trials. Drawing on the 8 year DarDar collaboration between Dartmouth and Muhimbili University of Health and Allied Sciences in Tanzania we will conduct 3 nutritional studies among HIV-infected women in Dar es Salaam. Study A will enroll 160 HIV+ and HIV- women who are either breast feeding (BF) or have active TB to conduct dietary interviews and focus groups to quantitate existing nutritional deficiencies and to define a culturally acceptable PCS. Studies B (118 HIV+ and 60 HIV- women who are breastfeeding) and C (118 HIV+ and 60 HIV- women with active TB) are randomized controlled trials which will compare the effects of 6 months of PCS + micronutrient supplement (MNS) vs. MNS alone on overall disease outcomes as well as specific surrogate markers of HIV disease, specific immune factors in breast milk and specific T cell responses against TB. Findings from these studies are expected to have a major impact on policies for nutritionally vulnerable HIV subpopulations.