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

缩小感染艾滋病毒的孕妇和婴儿的抗逆转录病毒治疗的研究空白

• 批准号: 10495240
• 负责人: Roger L Shapiro
• 金额: $ 121.49万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-24 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10495240
• 关键词: Address; Adult; Birth; Botswana; Child; Clinical Trials; Collaborations; Congenital Abnormality; Data; Data Sources; Development; Diagnosis; Exposure to; Funding; HIV; HIV vaccine; HIV-1; Human immunodeficiency virus test; Immune; Immune response; Infant; Infection; Infrastructure; Laboratories; Measures; Messenger RNA; Methodology; Modernization; Neural Tube Defects; Outcome; Performance; Pregnancy; Pregnant Women; Principal Investigator; RNA vaccine; Reporting; Research; Research Personnel; Research Priority; Series; Specimen; Surveillance Program; System; Techniques; Treatment Protocols; United States National Institutes of Health; Validation; Viral reservoir; Weight; Woman; Work; antiretroviral therapy; base; chromosomal location; cohesion; cohort; data infrastructure; data management; data sharing; efficacy study; experience; high risk infant; infancy; maternal weight; neonate; novel strategies; pediatric human immunodeficiency virus; pediatric human immunodeficiency virus infection; point of care; point-of-care diagnostics; precision medicine; programs; safety study; treatment guidelines; treatment optimization; treatment strategy

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.

总体项目摘要/摘要 孕妇的抗逆转录病毒治疗（ART）选择均落后于这些孕妇 对于成年人，反映了这些群体中现代艺术方案的大量研究差距。安全与功效 对怀孕中特定艺术方案的研究以及在婴儿早期开始现代艺术的策略的研究， 成为研究重点。在这里，我们提出了一系列相互关联的项目，以扩大科学目标 博茨瓦纳（Tsepamo 研究），并将其与现有计划提供的基础设施联系起来，以识别和治疗婴儿 艾滋病毒（早期婴儿治疗研究或EIT）。这四个拟议项目，由行政和 数据核心包括： 1）TSEPAMO Plus：扩大的先天性异常监视和模拟临床试验 评估重量对新艺术方案的出生结果的影响：扩大的监视计划 暴露于现代艺术方案后的神经管缺陷和其他先天性异常， 模拟临床试验，以解决与母体体重层面使用艺术方案有关的关键问题。 2）方法论：制定怀孕监视队列和新技术的报告标准 用于支持目标试验：创建怀孕群体和验证中的监视报告标准 ART方案比较的目标试验方法。 3）婴儿艾滋病毒测试和早期用于婴儿的Dolutegravir使用：针对目标设施的新方法 - 基于护理点的艾滋病毒测试，结合了使用DoluteGravir的优化艺术管理策略 从婴儿期开始。 4）开创性精确医学方法用于免疫控制儿科HIV-1感染：利用 共享数据和基础架构以有效地获得标本，该项目将从早期的艾滋病毒序列进行库存艾滋病毒序列 治疗的婴儿，测量和比较艺术方案之间的病毒储层和染色体定位 研究HIV儿童中对mRNA疫苗的免疫反应开始发育 博茨瓦纳儿童疫苗计划。 该P01汇集了一群经验丰富的调查人员，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架构 博茨瓦纳的节目。每个项目都涉及与怀孕期间艺术使用有关的关键科学问题和 在婴儿早期开始艺术的启动，他们将共同有效地弥合妇女和儿童的研究差距 与艾滋病毒。