Tsepamo Plus: Expanded Congenital Abnormalities Surveillance with an Emulated Clinical Trial to Evaluate Weight Impact on Birth Outcomes for Newer ART Regimens

Tsepamo Plus：通过模拟临床试验扩大先天性异常监测，以评估体重对新 ART 治疗方案出生结果的影响

• 批准号: 10696260
• 负责人: Roger L Shapiro
• 金额: $ 61.88万
• 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/10696260
• 关键词: Acquired Immunodeficiency Syndrome; Adopted; Adult; Africa; African; Anti-Retroviral Agents; Award; Birth; Birth Intervals; Botswana; Clinical Trials; Complex; Conceptions; Congenital Abnormality; Country; Data; Databases; Evaluation; Exclusion; Folic Acid; Funding; Guidelines; HIV; Health; Health Status Indicators; Hospitals; Incidence; Individual; Infant; Intake; International; Lamivudine; Link; Modeling; Modernization; Multiple Pregnancy; Neural Tube Defects; Outcome; Patients; Pattern; Pregnancy; Pregnancy Outcome; Pregnant Women; Premature Birth; Prevalence; Productivity; Program Research Project Grants; Publications; Rain; Regimen; Reporting; Research; Resource-limited setting; Risk; Safety; Seasons; Site; Small for Gestational Age Infant; System; Tenofovir; Time; Treatment Protocols; Update; Weight; Weight Gain; Woman; adverse birth outcomes; antiretroviral therapy; dietary; emtricitabine; experience; improved; maternal hypertension; maternal weight; neonatal death; novel; pre-exposure prophylaxis; pregnant; programs; randomized, clinical trials; secondary analysis; stillbirth; surveillance study; timeline; treatment guidelines; treatment program; trial comparing

Project Summary/Abstract, Tsepamo Plus (Project 1) Antiretroviral treatment (ART) guidelines depend upon safety and efficacy data in pregnancy, especially in resource-limited settings where programs rely on a single ART regimen as first-line treatment for all pregnant and non-pregnant adults. Current considerations for using modern ART regimens in pregnancy – especially those containing dolutegravir (DTG) and tenofovir alafenamide (TAF) – include understanding the risks for neural tube defects (NTDs) and for the effect of weight gain on pregnancy outcomes. The Tsepamo Study (R01HD080471, R01HD095766) is the largest pregnancy surveillance system in Africa, and has evaluated over 180,000 deliveries in Botswana since 2014. The study has provided critical safety data and treatment guidance related to specific ART regimens that have been adopted for early use within the Botswana ART program. In 2018, the Tsepamo Study demonstrated a potential association with DTG and NTDs, and while this concern has decreased over time following expanded surveillance, it has not disappeared. Ongoing NTD surveillance is required both for DTG and for other new antiretroviral agents. New considerations regarding weight gain with modern ART regimens have also been analyzed successfully in Tsepamo, but further data stratified by baseline maternal weight groups are needed. The existing Tsepamo award was funded to continue birth surveillance through December 2022, and the P01 mechanism can extend surveillance for 4 additional years from January 2023 through December 2026. This will allow the completion of aims that include: 1) ongoing surveillance to understand and characterize the neural tube defect risk associated with DTG over a longer period, and with additional evaluation of dietary folic acid intake; 2) a new aim to conduct an emulated clinical trial comparing the most relevant ART regimens when used at different weight strata; and 3) new aims that utilize a unique identifier to capture data across multiple pregnancies for the first time in our surveillance. These novel aims take advantage of the unique ART landscape in Botswana, and build on the scientific findings from our highly productive surveillance system. Data generated from this study will be critical for updating international guidelines for the use of ART in pregnancy.

项目摘要/摘要，Tsepamo Plus（项目1） 抗逆转录病毒治疗（ART）指南取决于怀孕的安全和效率数据，尤其是在 资源有限的设置，计划依靠单一艺术方案作为所有怀孕的一线治疗 和非怀孕的成年人。当前考虑在怀孕时使用现代艺术方案的考虑 - 尤其是 含有DoluteGravir（DTG）和Tenofovir alafenamide（TAF）的人 - 包括了解神经元的风险 管缺陷（NTD）和体重增加对妊娠结局的影响。 TSEPAMO研究 （R01HD080471，R01HD095766）是非洲最大的怀孕监视系统，并且已经评估了 自2014年以来，博茨瓦纳的180,000次交付。该研究提供了关键的安全数据和治疗指南 与在博茨瓦纳艺术计划中采用的特定艺术方案有关。在 2018年，TSEPAMO研究证明了与DTG和NTD的潜在关联，尽管这种关注已有 扩大监视后随着时间的流逝而减少，尚未消失。正在进行的NTD监视是 DTG和其他新型抗逆转录病毒药物都需要。关于体重增加的新考虑 现代艺术方案也已在TSEPAMO中成功进行了分析，但根据基线进行了进一步的数据 需要孕产妇体重组。现有的TSEPAMO奖旨在继续出生监视 到2022年12月，P01机制可以从1月起将监视延长4年 2023年至2026年12月。这将允许完成目标：1）正在进行的监视 了解并表征与DTG相关的神经管缺陷风险，并与 饮食叶酸摄入的其他评估； 2）进行模拟的临床试验的新目标 最相关的艺术方案在不同的体重层次上使用； 3）使用唯一标识符的新目标 在我们的监视中，第一次捕获多个怀孕的数据。这些小说的目标是 博茨瓦纳独特的艺术风景的优势，并以我们高度的科学发现为基础 生产监视系统。这项研究产生的数据对于更新国际至关重要 在怀孕中使用艺术的指南。