Expansion of research and mentoring to improve birth outcomes and treatment outcomes among HIV-affected children in Botswana

摘要/摘要 我正在申请K24奖项，目的是扩大NIH资助的两项研究的范围 博茨瓦纳和创建一个组合数据集，以最大限度地利用现有数据和临床样本 一群人。在过去的18年里，我在博茨瓦纳建立了一个成功的研究项目，重点是 预防母婴传播艾滋病毒(母婴传播)，了解婴儿的不良分娩结果 在子宫内暴露于抗逆转录病毒药物，并提高艾滋病毒感染儿童和接触艾滋病毒儿童的存活率。我 在我的职业生涯中，我成功地指导或共同指导了30多名年轻调查人员，但通过K24 机制I可以提高我的指导专业知识，并为受训者扩大机会。My K24-支持 研究将有以下目标：1)扩大对猪瘟病毒学和免疫学预测因素的分析 使用广谱中和单抗作为一种节省艺术的方法后的成功结果 对一群接受早期治疗的艾滋病毒感染儿童进行干预；2)扩大现有NIH- 通过增加首次出生结果监测，为博茨瓦纳的全国出生监测提供资金 多洛替格列韦和边缘结构模型模拟分娩的临床对比试验 妊娠期间使用的ART方案的结果；以及3)结合来自6个大型研究队列的数据 评估博茨瓦纳感染艾滋病毒的未感染儿童死亡率下降的原因。我的训练 计划将具体扩展我在母胎医学方面的专业知识，我的指导计划将包括一个团队 在波士顿和博茨瓦纳有效利用大型临床试验和现有临床试验机会的方法 数据集和样本。

Summary / Abstract I am applying for a K24 award with the goals of expanding the scope of two NIH-funded research studies in Botswana and creating a combined dataset to maximally utilize existing data and specimens from clinical cohorts. In the past 18 years, I have built a successful research program in Botswana with a focus on the prevention of mother-to-child HIV transmission (PMTCT), understanding adverse birth outcomes among infants exposed to antiretrovirals in utero, and improving survival among HIV-infected and HIV-exposed children. I have successfully mentored or co-mentored over 30 young investigators in my career, but through a K24 mechanism I can improve my mentoring expertise and expand opportunities for mentees. My K24-supported research will have the following aims: 1) to expand analyses of the virologic and immunologic predictors of successful outcomes following use of a broadly neutralizing monoclonal antibody as an ART-sparing intervention in a cohort of early-treated HIV-infected children; 2) to expand the objectives of existing NIH- funded nationwide birth surveillance in Botswana by adding first-ever birth outcomes surveillance of Dolutegravir-exposed infants and marginal structural modeling to simulate a clinical trial comparing birth outcomes by ART regimens used in pregnancy; and 3) to combine data from 6 large research cohorts to evaluate the reasons for declining mortality among HIV-exposed uninfected children in Botswana. My training plan will specifically expand my expertise in maternal-fetal medicine, and my mentoring plan will involve a team approach in Boston and Botswana to efficiently utilize opportunities within both large clinical trials and existing datasets and specimens.