Health of HIV-Infected Mothers after pMTCT, Botswana

描述（由申请人提供）：孕产妇健康问题是一个重要的，但研究不足的方面，旨在防止母婴传播艾滋病毒-1（母婴传播）在发展中国家的计划。在这方面，关于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进行母乳喂养是否与产妇发病率和死亡率过高有关; 2）以前曾服用单剂量奈韦拉平预防母婴传播的妇女对含奈韦拉平的联合抗逆转录病毒疗法的反应，鉴于单剂量NVP后经常出现耐药HIV-1。目前，在博茨瓦纳，受艾滋病毒感染的母亲正在参加一项由NICHD资助的随机临床试验，研究预防母婴传播的战略。妇女被随机分为两组，一组接受短期齐多夫定+单剂量NVP的围产期预防治疗，另一组接受齐多夫定单药治疗，母乳喂养时给予婴儿预防性齐多夫定，另一组接受配方奶粉喂养。在这项研究中，艾滋病妇女将获得政府ART计划的一线含NVP的ART方案。本研究的主要目的是：1.研究随机婴儿喂养策略（母乳喂养与配方奶粉喂养）与母亲患艾滋病或死亡时间之间的关系。评估既往在分娩期间接受过单剂量NVP与安慰剂的女性中，在开始含NVP的ART后52周时出现病毒学应答（血浆HIV-1 RNA < 400拷贝/ mL）的女性比例。次要目的包括阐明HIV感染母亲母乳喂养可能导致的孕产妇发病率和死亡率过高的病因，包括微量营养素缺乏症;在分娩期间接受单剂量NVP与安慰剂的妇女中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对ART的耐受性、安全性和依从性。这一已经存在的接受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.