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

项目概要/摘要 为感染艾滋病毒的孕妇和儿童提供的抗逆转录病毒治疗方案落后于这些方案， 这反映了现代ART疗法在这些人群中的巨大研究缺口。安全性和有效性 对妊娠期特定ART方案的研究，以及在婴儿早期开始现代ART的策略， 成为研究重点。在这里，我们提出了一系列相互关联的项目，扩大了科学目标 和数据利用的一个宝贵的NIH资助的全国出生监测系统在博茨瓦纳（Tsepamo 研究），并将其与现有的用于识别和治疗婴儿的计划所提供的基础设施连接起来 早期婴儿治疗研究（EIT）四个拟议项目以行政和 数据核心包括： 1)Tsepamo Plus：扩大先天性肛门畸形监测和模拟临床试验， 评价体重对较新ART方案出生结局的影响：一项扩大的监测计划 神经管缺陷和其他先天性异常暴露于现代ART方案后， 模拟临床试验，以解决关键问题有关使用抗逆转录病毒疗法的产妇体重分层。 2)方法学：制定妊娠监测队列和新技术的报告标准 支持性目标试验：创建妊娠队列监测报告标准和验证 ART方案比较的靶向试验方法。 3)婴儿的床旁艾滋病毒检测和早期多鲁特韦使用：一种针对目标设施的新方法- 基于床旁艾滋病毒检测，结合使用度鲁特韦的优化ART管理策略 从婴儿早期开始 4)儿童HIV-1感染免疫控制的开创性精准医学方法：利用 共享数据和基础设施，以有效地获得标本，该项目将从早期- 治疗的婴儿，测量和比较ART方案之间的病毒储库和染色体定位，以及 研究HIV感染儿童对mRNA疫苗的免疫反应，以开始发展mRNA HIV 为博茨瓦纳的儿童提供疫苗。 这个P01汇集了一组经验丰富的研究人员，他们将使用 Tsepamo和EIT研究提供的独特数据源和出色的物理基础设施 博茨瓦纳的节目。每个项目都涉及与怀孕期间使用抗逆转录病毒疗法有关的关键科学问题， 在婴儿早期开始抗逆转录病毒治疗，它们将有效地缩小妇女和儿童的研究差距 感染了艾滋病毒

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.