Closing Research Gaps in Antiretroviral Treatment for Pregnant Women and Infants Living with HIV

总体项目摘要/摘要 孕妇和携带艾滋病毒的儿童的抗逆转录病毒治疗(ART)选择已经落后于 对于成年人来说，反映了这些群体中对现代艺术养生法的实质性研究差距。安全性和有效性 对怀孕期间特定的ART养生法的研究，以及在婴儿早期开始现代ART的策略，有 成为研究的重点。在这里，我们提出了一系列相互关联的项目，以扩展科学目标 国家卫生研究院资助的博茨瓦纳全国出生监测系统(TSepamo)的数据利用 研究)，并将其与现有的婴儿识别和治疗方案提供的基础设施连接起来 感染艾滋病毒(早期婴儿治疗研究，简称EIT)。四个拟议的项目，以行政和 数据核心，包括： 1)TSepamo Plus：扩大先天性异常监测和模拟临床试验 评估新ART方案的体重对出生结局的影响：一项扩大的监测计划 对于神经管缺陷和其他先天性异常，暴露在现代ART疗法中，以及 模拟临床试验，以解决与母亲体重分层使用ART方案相关的关键问题。 2)方法：制定妊娠监测队列的报告标准和新技术 用于支持目标试验：在妊娠队列中建立监测报告标准和验证 ART方案比较的靶向试验方法。 3)针对婴儿的护理点艾滋病毒检测和早期使用多洛替格列韦：目标设施的新方法-- 基于护理点艾滋病毒检测，结合使用多洛替格韦的优化ART管理策略 从婴儿期就开始了。 4)开创用于儿童HIV-1感染免疫控制的精确医学方法：利用 共享数据和基础设施为了高效地获取样本，该项目将从早期开始存储艾滋病毒序列- 接受治疗的婴儿，测量和比较ART方案之间的病毒库和染色体定位，以及 研究HIV儿童对信使核糖核酸疫苗的免疫应答以开始形成信使核糖核酸 博茨瓦纳儿童疫苗计划。 P01汇聚了一群经验丰富的研究人员，他们将利用 TSepamo和EIT研究提供的独特数据源和出色的物理基础设施 在博茨瓦纳的项目。每个项目都解决了与怀孕期间使用抗逆转录病毒药物有关的关键科学问题 在婴儿期早期启动ART，他们的共同努力将有效地缩小妇女和儿童的研究差距 艾滋病毒携带者。

Overall Project Summary/Abstract Antiretroviral treatment (ART) options for pregnant women and children living with HIV have fallen behind those for adults, reflecting the substantial research gap for modern ART regimens in these groups. Safety and efficacy studies of specific ART regimens in pregnancy, and strategies for starting modern ART in early infancy, have become research priorities. Here we propose a series of interrelated projects that expand the scientific objectives and data utilization of a valuable NIH-funded nationwide birth surveillance system in Botswana (the Tsepamo Study), and connect it with the infrastructure provided by an existing program for identifying and treating infants with HIV (the Early Infant Treatment Study, or EIT). The four proposed projects, anchored by administrative and data cores, include: 1) Tsepamo Plus: Expanded Congenital Abnormalities Surveillance and an Emulated Clinical Trial to Evaluate Weight Impact on Birth Outcomes for Newer ART Regimens: an expanded surveillance program for neural tube defects and other congenital abnormalities following exposure to modern ART regimens, and an emulated clinical trial to address critical questions related to use of ART regimens by maternal weight strata. 2) Methodology: Developing Reporting Criteria for Pregnancy Surveillance Cohorts and New Techniques for Supporting Target Trials: the creation of surveillance reporting criteria in pregnancy cohorts and validation of a target trial approach to ART regimen comparisons. 3) Point-of-Care HIV Testing and Early Dolutegravir Use for Infants: a new approach to targeted facility- based point-of-care HIV testing, combined with an optimized ART management strategy that uses dolutegravir from early infancy. 4) Pioneering Precision Medicine Approaches for Immune Control of Pediatric HIV-1 Infection: utilizing shared data and infrastructure to efficiently obtain specimens, this project will bank HIV sequences from early- treated infants, measure and compare viral reservoir and chromosomal positioning between ART regimens, and study immune responses to mRNA vaccines among children with HIV to begin development of an mRNA HIV vaccine program for children in Botswana. This P01 brings together a group of experienced investigators who will forge a cohesive research program using the unique data sources and outstanding physical infrastructure available from the Tsepamo and EIT research programs in Botswana. Each project addresses key scientific issues related to ART use during pregnancy and initiation of ART in early infancy, and together they will efficiently close research gaps for women and children with HIV.