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.

项目概要/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 资源有限的环境，方案依赖于单一的ART方案作为所有孕妇的一线治疗 未怀孕的成年人。目前在妊娠期使用现代ART方案的考虑因素-特别是 那些含有度鲁特韦（DTG）和替诺福韦艾拉酚胺（TAF）的药物-包括了解神经系统疾病的风险， 输卵管缺陷（NTD）和体重增加对妊娠结局的影响。Tsepamo研究 （R 01 HD 080471，R 01 HD 095766）是非洲最大的妊娠监测系统， 自2014年以来，博茨瓦纳有18万次分娩。该研究提供了关键的安全性数据和治疗指导 与博茨瓦纳抗逆转录病毒治疗计划中早期使用的特定抗逆转录病毒治疗方案有关。在 2018年，Tsepamo研究证明了DTG和NTD的潜在关联，虽然这种担忧 随着时间的推移，随着监测的扩大，它并没有消失。正在进行的NTD监测是 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 在Tsepamo中也成功分析了现代ART方案，但进一步的数据按基线分层 需要母体重量组。现有的Tsepamo奖获得资助，继续进行出生监测 到2022年12月，P01机制可以从1月起将监测延长4年 2023年至2026年12月。这将有助于实现以下目标：1）持续监测， 了解和描述与DTG相关的神经管缺陷风险， 对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， 当用于不同体重分层时，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胎妊娠的数据。这些新的目标需要 博茨瓦纳独特的艺术景观的优势，并建立在我们高度重视的科学发现的基础上， 生产监督体系。本研究生成的数据对于更新国际 在怀孕期间使用抗逆转录病毒疗法的指导方针。