Health of HIV-Infected Mothers after pMTCT, Botswana

描述（由申请人提供）：在发展中国家，孕产妇健康问题是预防HIV-1母婴传播（MTCT）项目的一个重要但尚未得到充分研究的方面。在这种情况下，关于孕产妇保健的两个最重要和最紧迫的问题是：1)感染艾滋病毒的妇女的母乳喂养是否与产妇发病率和死亡率过高有关；2)鉴于单剂量NVP后经常出现耐药艾滋病毒-1，以前服用过单剂量NVP以预防MTCT的妇女对含奈韦拉平（NVP）的联合抗逆转录病毒治疗（ART）的反应。感染艾滋病毒的母亲目前正在博茨瓦纳参加一项由联合国儿童基金会资助的随机临床试验，该试验正在研究预防母婴传播的战略。妇女被随机分配到短疗程齐多夫定+单剂量NVP的围产期预防或单独使用齐多夫定，并在给予婴儿预防性齐多夫定的同时进行母乳喂养或配方喂养。在这项研究中，患有艾滋病的妇女将接受政府抗逆转录病毒治疗计划的一线含nvp的抗逆转录病毒治疗方案。本建议的主要目标是：1。研究随机婴儿喂养策略（母乳喂养与配方喂养）与产妇艾滋病或死亡时间之间的关系；评估在分娩期间接受单剂量NVP和安慰剂的妇女中，在开始含NVP的ART治疗52周后出现病毒学应答（血浆HIV-1 RNA < 400拷贝/ mL）的妇女比例。次要目标包括阐明受艾滋病毒感染的母亲与母乳喂养有关的可能过高的产妇发病率和死亡率的病因，包括微量营养素缺乏；先前在分娩期间接受单剂量NVP与安慰剂的妇女出现基因型耐药和病毒学失败；以及博茨瓦纳孕妇和产后妇女抗逆转录病毒治疗的耐受性、安全性和依从性。这一已经获得抗逆转录病毒治疗的队列提供了一个独特的机会，可以用相对较少的额外资源投资来回答具有重大公共卫生影响的问题。

DESCRIPTION (provided by applicant): Maternal health concerns are an important but understudied aspect of programs designed to prevent mother-to-child HIV-1 transmission (MTCT) in the developing world. Two of the most important and urgent questions regarding maternal health in this context are 1) whether breastfeeding by HIV-infected women is associated with excess maternal morbidity and mortality, and 2) the response to nevirapine (NVP)-containing combination antiretroviral therapy (ART) among women who have previously taken single-dose NVP for the prevention of MTCT, given the frequent emergence of drug resistant HIV-1 after single-dose NVP. HIV-infected mothers are currently being enrolled in a NICHD-funded randomized clinical trial in Botswana that is studying strategies for MTCT prevention. Women are randomized to either perinatal prophylaxis with short course zidovudine + single-dose NVP or to zidovudine alone, and to either breastfeed while giving their infant prophylactic zidovudine or to formula-feed. Women with AIDS in this study will be offered the Government ART program first-line NVP-containing ART regimen. The primary objectives of this proposal are: 1.To examine the association between randomized infant feeding strategy (breast- versus formula feeding) and time to maternal AIDS or death, and 2. To assess the proportion of women with virologic response (plasma HIV-1 RNA < 400 copies / mL) at 52 weeks after initiating NVP-containing ART among women who previously received single-dose NVP versus placebo during labor. Secondary objectives include elucidation of the etiology of possible excess maternal morbidity and mortality associated with breastfeeding by HIV-infected mothers, including micronutrient deficiency; the emergence of genotypic resistance and virologic failure in women who previously received single-dose NVP versus placebo during labor; and the tolerability and safety of and adherence to ART among pregnant and postpartum women in Botswana. This already-existing cohort with access to ART provides a unique opportunity to answer questions that have significant public health implications with a relatively small investment of additional resources.