Growth Trends and Mortality Risks Among HIV-exposed Infants in Botswana

说明(申请人提供)：通过在怀孕和哺乳期间使用抗逆转录病毒药物，发展中国家的母婴艾滋病毒传播(MTCT)已有所减少。尽管预防艾滋病毒母婴传播(PMTCT)项目的成功基准历来侧重于艾滋病毒的垂直传播率，但在资源有限的情况下，在怀孕和母乳喂养中使用抗逆转录病毒药物已将重点转移到总体无艾滋病毒婴儿存活率上。在资源有限的环境中，感染艾滋病毒的未感染婴儿(艾滋病毒-EUI)的发病率和死亡率高于未感染艾滋病毒的婴儿，但造成这种差异的根本原因尚不清楚。查明导致艾滋病毒-EUI患者发病率和死亡率升高的因素，并确定提高无艾滋病毒存活率的方法，对公共卫生具有至关重要的意义。十多年来，博茨瓦纳-哈佛公共卫生学院艾滋病研究所伙伴关系(BHP)一直与博茨瓦纳卫生部合作，开展防止母婴传播和婴儿存活研究。利用必和必拓的研究基础设施，我的具体研究目标是：1)评估婴儿出生时维生素D水平与生命头24个月发病率/死亡率之间的关系；2)评估艾滋病毒感染婴儿中的维生素D水平是否与未接触艾滋病毒婴儿的维生素D水平不同；3)评估与未接触艾滋病毒婴儿相比，艾滋病毒感染婴儿的发病率和死亡率增加的风险因素；4)确定母乳喂养期间母亲的HAART是否与母乳喂养期间艾滋病毒感染婴儿与婴儿预防奈韦拉平相比有利的纵向生长模式有关；5)确定艾滋病毒感染婴儿中有利生长模式的潜在调节因素。我的研究将嵌套在由美国国立卫生研究院资助的博茨瓦纳艾滋病毒感染婴儿的大型临床试验中，我还将在这些诊所创建一个未感染艾滋病毒的婴儿的对照队列。我将得到我的共同导师(罗杰·夏皮罗博士和马克斯·埃塞克斯博士)以及我的顾问团队(沙欣·洛克曼博士、迈克尔·休斯博士、瓦菲·法齐博士和约瑟夫·马克马博士)的支持。这些研究人员在母婴传播预防和婴儿存活领域拥有丰富的工作经验。通过我的具体研究目标和职业发展计划，我希望成为一名独立的调查员，并实现我的长期目标，即在资源有限的情况下改善艾滋病毒感染婴儿的健康和存活率。 公共卫生相关性：博茨瓦纳感染艾滋病毒但未受感染的婴儿(艾滋病毒-EUI)人数不断增加。这些婴儿的发病率和死亡率比那些未接触艾滋病毒的婴儿更高。这项研究将确定与艾滋病毒-EUI发病率和死亡率增加有关的可改变的风险因素，使用的是由国立卫生研究院资助的大型队列以及新的未暴露于艾滋病毒的婴儿队列。潜在可改变的风险因素，包括产妇和婴儿维生素D水平，将是今后制定干预措施的重点领域 以提高这一弱势群体的存活率。

DESCRIPTION (provided by applicant): Mother-to-child HIV transmission (MTCT) in the developing world has decreased through the use of antiretrovirals in pregnancy and breastfeeding. Whereas the benchmark of success for programs designed to prevent mother-to-child HIV transmission (PMTCT) has historically focused on vertical HIV-transmission rates, use of antiretrovirals in pregnancy and breastfeeding in resource limited settings has shifted the focus to overall HIV-free infant survival. HIV-exposed uninfected infants (HIV-EUIs) experience higher rates of morbidity and mortality than HIV-unexposed infants in resource limited settings, but the underlying reasons for this disparity are unknown. Identifying the factors that contribute to higher morbidity and mortality among HIV-EUIs and determining methods to improve HIV-free survival is of critical public health importance. The Botswana-Harvard School of Public Health AIDS Institute Partnership (BHP) has been working with the Botswana Ministry of Health to conduct PMTCT and infant survival research for over a decade. Using the research infrastructure of BHP, my specific research aims are: 1) to evaluate the association between infant vitamin D levels at birth and morbidity/mortality in the first 24 months of life, 2) to evalate whether vitamin D levels in HIV-EUIs differ from that of HIV-unexposed infants, 3) to evaluate risk factors for increased morbidity and mortality in HIV-EUIs compared with HIV-unexposed infants, 4) to determine if maternal HAART during breastfeeding is associated with favorable longitudinal growth patterns among HIV-EUIs compared with infant nevirapine prophylaxis during breastfeeding, and 5) to identify potential mediators of favorable growth patterns among HIV-EUIs. My research will be nested within a large NIH-funded clinical trial of HIV-exposed infants in Botswana, and I will also create a comparator cohort of HIV-unexposed infants at these same clinic sites. I will be supported by my co-mentors (Drs. Roger Shapiro and Max Essex), as well as my advisory team (Drs. Shahin Lockman, Michael Hughes, Wafaie Fawzi and Joseph Makhema). These researchers have extensive experience working in the field of MTCT prevention and infant survival. Through my specific research aims and career development plan, I hope to emerge as an independent investigator and achieve my long-term goal of improving the health and survival of HIV-exposed infants in resource limited settings. PUBLIC HEALTH RELEVANCE: There is an increasing number of HIV-exposed but uninfected infants (HIV-EUIs) in Botswana. These infants have higher rates of morbidity and mortality than those who are HIV-unexposed. This study will identify modifiable risk factors associated with increased rates of morbidity and mortality of HIV-EUIs using a large, ongoing NIH-funded cohort as well a new cohort of HIV-unexposed infants. Potentially modifiable risk factors, including maternal and infant Vit D levels, will be an area of focus in order to develop future interventions to improve survival in this vulnerable group.