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: 10495244
• 负责人: Roger L Shapiro
• 金额: $ 55.73万
• 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/10495244
• 关键词: Acquired Immunodeficiency Syndrome; Adopted; Adult; Africa; African; Anti-Retroviral Agents; Award; Birth; Birth Intervals; Botswana; Childhood Acute Lymphocytic Leukemia; Clinical Trials; Complex; Conceptions; Congenital Abnormality; Country; Data; Databases; Evaluation; Folic Acid; Funding; Guidelines; HIV; Health; Health Status Indicators; Hospitals; Incidence; Individual; Infant; Institutes; Intake; International; Lamivudine; Link; Modeling; Modernization; Multiple Pregnancy; Neural Tube Defects; Outcome; Patients; Pattern; Pregnancy; Pregnancy Outcome; Pregnant Women; Premature Birth; Prevalence; Program Research Project Grants; Publications; Rain; Randomized Clinical Trials; Regimen; Reporting; Research; Resource-limited setting; Risk; Safety; Site; Small for Gestational Age Infant; System; Tenofovir; Time; TimeLine; Treatment Protocols; Update; Weight; Weight Gain; Woman; adverse birth outcomes; antiretroviral therapy; base; dietary; emtricitabine; experience; improved; maternal hypertension; maternal weight; neonatal death; novel; pre-exposure prophylaxis; pregnant; programs; secondary analysis; stillbirth; surveillance study; 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)指南取决于妊娠期的安全性和有效性数据，特别是在 资源有限的情况下，方案依赖单一的ART方案作为所有孕妇的一线治疗 以及未怀孕的成年人。目前考虑在怀孕期间使用现代ART养生法--尤其是 那些含有多洛替格列韦(DTG)和替诺福韦丙氨酰胺(TAF)的药物-包括了解对神经的风险 输卵管缺陷(NTDS)和体重增加对妊娠结局的影响。特塞帕莫研究 (R01HD080471，R01HD095766)是非洲最大的妊娠监测系统，已评估超过 自2014年以来，博茨瓦纳共交付了18万份快递。这项研究提供了关键的安全数据和治疗指导 与博茨瓦纳抗逆转录病毒治疗方案中早期采用的具体抗逆转录病毒疗法有关。在……里面 2018年，TSepamo的研究表明了与DTG和NTDS的潜在关联，虽然这一担忧已经 虽然在扩大监测后随着时间的推移有所下降，但它并没有消失。正在进行的NTD监视是 DTG和其他新的抗逆转录病毒药物都需要。关于体重增加的新考虑 现代抗逆转录病毒疗法在特塞帕莫也得到了成功的分析，但进一步的数据按基线分层 母体体重组是必要的。现有的特塞帕莫奖的资金用于继续进行出生监测 到2022年12月，P01机制可以从1月起再延长4年 2023年至2026年12月。这将使目标得以完成，这些目标包括：1)持续监测 了解和描述较长时期内与DTG相关的神经管缺陷风险，以及 对膳食叶酸摄入量的额外评估；2)进行一项模拟临床试验的新目标，比较 在不同重量层使用时最相关的ART养生法；以及3)利用唯一识别符的新目标 在我们的监测中第一次捕获多个怀孕的数据。这些新奇的目标 利用博茨瓦纳独特的艺术景观，并以我们高度重视的科学发现为基础 生产性监视系统。这项研究产生的数据将对更新国际 妊娠期抗逆转录病毒药物的使用指南。