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

基本信息

批准号：
10696257
负责人：
Roger L Shapiro
金额：
$ 120.26万
依托单位：
HARVARD SCHOOL OF PUBLIC HEALTH
依托单位国家：
美国
项目类别：
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/10696257
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 chromosomal location cohort data management data sharing efficacy study experience falls forging 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

项目摘要

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.

总体项目总结/摘要针对感染艾滋病毒的孕妇和儿童的抗逆转录病毒治疗（ART）选择已经落后于其他治疗方案对于成年人来说，反映了现代 ART 治疗方案在这些群体中的巨大研究差距。安全性和有效性对妊娠期特定 ART 治疗方案以及在婴儿早期开始现代 ART 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来扩展科学目标博茨瓦纳由美国国立卫生研究院 (NIH) 资助的全国性出生监测系统（Tsepamo）的数据利用研究），并将其与现有项目提供的基础设施连接起来，用于识别和治疗婴儿感染艾滋病毒（早期婴儿治疗研究，或 EIT）。这四个拟议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的 ART 治疗方案中体重对出生结果的影响：扩大的监测计划针对接受现代 ART 疗法后的神经管缺陷和其他先天性异常，以及模拟临床试验，以解决与按母亲体重分层使用 ART 方案相关的关键问题。 2) 方法论：制定妊娠监测队列和新技术的报告标准支持目标试验：制定妊娠队列监测报告标准并进行验证 ART 方案比较的目标试验方法。 3) 婴儿护理点艾滋病毒检测和早期使用多替拉韦：针对目标设施的新方法- 基于护理点的 HIV 检测，结合使用多替拉韦的优化 ART 管理策略从婴儿早期开始。 4) 儿科 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获取样本，该项目将从早期开始储存艾滋病毒序列接受治疗的婴儿，测量并比较 ART 治疗方案之间的病毒库和染色体定位，以及研究 HIV 儿童对 mRNA 疫苗的免疫反应，开始开发 mRNA HIV 博茨瓦纳儿童疫苗计划。这个 P01 汇集了一群经验丰富的研究人员，他们将使用以下方法打造一个有凝聚力的研究计划： 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计划。每个项目都解决与怀孕期间使用 ART 相关的关键科学问题，以及在婴儿早期启动抗逆转录病毒疗法，他们将共同有效地缩小妇女和儿童的研究差距患有艾滋病毒。