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

描述（由申请人提供）：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）有所减少。以往，预防母婴艾滋病毒传播（PMTCT）项目的成功基准关注的是艾滋病毒的垂直传播率，而在资源有限的情况下，在怀孕和哺乳期间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，暴露于艾滋病毒的未感染婴儿（HIV-EUIs）的发病率和死亡率高于未暴露于艾滋病毒的婴儿，但造成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）与博茨瓦纳卫生部合作开展预防母婴传播和婴儿生存研究已有十多年。利用BHP的研究基础设施，我的具体研究目标是：1)评估出生时婴儿维生素D水平与出生后24个月的发病率/死亡率之间的关系；2)评估hiv - eui婴儿的维生素D水平是否与未暴露的婴儿不同；3)评估与未暴露的婴儿相比，hiv - eui婴儿发病率和死亡率增加的危险因素。4)确定与母乳喂养期间的婴儿奈韦拉平预防相比，母乳喂养期间的母亲HAART是否与hiv - eui有利的纵向生长模式相关；5)确定hiv - eui有利生长模式的潜在介质。我的研究将嵌套在nih资助的博茨瓦纳艾滋病毒感染婴儿的大型临床试验中，我还将在这些相同的诊所地点创建一个未感染艾滋病毒的婴儿的比较队列。我将得到我的共同导师（博士）的支持。Roger Shapiro和Max Essex)，以及我的顾问团队(dr。Shahin Lockman, Michael Hughes， Wafaie Fawzi和Joseph Makhema)。这些研究人员在母婴传播预防和婴儿生存领域有着丰富的工作经验。通过我具体的研究目标和职业发展规划，我希望成为一名独立的研究者，实现我在资源有限的环境下改善艾滋病毒暴露婴儿的健康和生存的长期目标。

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.