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，尤其是在妊娠期 资源有限的环境，项目依赖单一 ART 方案作为所有孕妇的一线治疗 和非怀孕成人目前在怀孕期间使用现代 ART 方案的考虑因素 - 特别是 含有多替拉韦 (DTG) 和替诺福韦艾拉酚胺 (TAF) 的药物 – 包括了解神经风险 输卵管缺陷 (NTD) 以及体重增加对妊娠结局的影响。 （R01HD080471、R01HD095766）是非洲最大的妊娠监测系统，已评估超过 自 2014 年以来，博茨瓦纳已分娩 180,000 例。该研究提供了关键的安全数据和治疗指导 与博茨瓦纳 ART 计划中早期使用的特定 ART 方案相关。 2018 年，Tsepamo 研究证明了与 DTG 和 NTD 的潜在关联，虽然这种担忧已经 随着监测范围的扩大，持续的 NTD 监测逐渐减少，但并未消失。 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因素。 现代 ART 治疗方案也在 Tsepamo 中得到了成功分析，但进一步的数据按基线分层 现有的 Tsepamo 奖需要资助以继续进行出生监测。 至 2022 年 12 月，P01 机制可从 1 月起将监测再延长 4 年 2023 年至 2026 年 12 月。这将有助于完成以下目标：1) 持续监测 了解并表征与 DTG 相关的较长时期的神经管缺陷风险，以及 膳食叶酸摄入量的额外评估；2) 进行模拟临床试验的新目标 在不同体重层使用时最相关的 ART 方案；以及 3) 利用唯一标识符的新目标 在我们的监测中首次捕获多次怀孕的数据。 充分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 这项研究产生的数据对于更新国际监测系统至关重要。 妊娠期使用 ART 的指南。