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

描述（由申请人提供）：在发展中国家，通过在怀孕和哺乳期间使用抗逆转录病毒药物，母婴艾滋病毒传播（MTCT）已经减少。虽然旨在预防母婴艾滋病毒传播的方案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，在怀孕和母乳喂养期间使用抗逆转录病毒药物已将重点转移到无艾滋病毒婴儿的总体存活率。在资源有限的环境中，暴露于艾滋病毒的未感染婴儿（HIV-EUI）的发病率和死亡率高于未暴露于艾滋病毒的婴儿，但这种差异的根本原因尚不清楚。确定导致艾滋病毒感染者发病率和死亡率较高的因素，并确定提高无艾滋病毒生存率的方法，对公共卫生至关重要。博茨瓦纳-哈佛大学公共卫生学院艾滋病研究所伙伴关系（BHP）十多年来一直与博茨瓦纳卫生部合作开展预防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）评价出生时婴儿维生素D水平与出生后24个月内发病率/死亡率之间的关系，2）评价HIV-EUI中的维生素D水平是否与未暴露于HIV的婴儿不同，3）评价与未暴露于HIV的婴儿相比，HIV-EUI中发病率和死亡率增加的风险因素，4）确定与母乳喂养期间婴儿奈韦拉平预防相比，母乳喂养期间母亲HAART是否与HIV-EUI中有利的纵向生长模式相关，以及5）确定HIV-EUI中有利生长模式的潜在介质。我的研究将嵌套在一个大型的NIH资助的艾滋病毒暴露的婴儿在博茨瓦纳的临床试验，我也将创建一个比较队列的艾滋病毒未暴露的婴儿在这些相同的诊所网站。我将得到我的共同导师（Roger Shapiro博士和Max埃塞克斯博士）以及我的顾问团队（Shahin Lockman博士、Michael Hughes博士、Wafaie Fawzi博士和Joseph Makhema博士）的支持。这些研究人员在预防母婴传播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研究者，并实现我的长期目标，即在资源有限的环境中改善艾滋病毒暴露婴儿的健康和生存。 公共卫生相关性：在博茨瓦纳，暴露于艾滋病毒但未感染的婴儿（HIV-EUI）数量不断增加。这些婴儿的发病率和死亡率高于未感染艾滋病毒的婴儿。这项研究将使用一个大型的、正在进行的NIH资助的队列以及一个新的HIV未暴露婴儿队列，确定与HIV EUI发病率和死亡率增加相关的可改变的风险因素。潜在的可改变的风险因素，包括孕产妇和婴儿维生素D水平，将是制定未来干预措施的重点领域 来改善这个弱势群体的生存状况。

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.