Surveillance Monitoring for ART Toxicities (SMARTT) Study

ART 毒性监测 (SMARTT) 研究

• 批准号: 10065443
• 负责人: PAIGE L WILLIAMS
• 金额: $ 14.53万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-18 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10065443
• 关键词: 17 year old; 5 year old; Adult; Adverse effects; Adverse event; Age; Anti-Retroviral Agents; Birth; Child; Clinical; Conceptions; Databases; Enrollment; Epidemiologic Methods; Evaluation; Funding; Future; Goals; Growth; Guidelines; HIV; Health; Hearing; Infant; Infection; Insulin; International; International Maternal Pediatric Adolescent AIDS Clinical Trials; Investigation; Laboratories; Language; Lipids; Longterm Follow-up; Maternal Health; Maternal and Child Health; Metabolic; Monitor; Mothers; Oral health; Outcome; Pediatric HIV/AIDS Cohort Study; Perinatal; Periodicity; Pharmaceutical Preparations; Pregnancy; Pregnant Women; Premature Birth; Public Health; Recommendation; Regimen; Reporting; Research; Research Design; Resolution; Risk; Safety; Statistical Methods; Suggestion; System; Tenofovir; Time; Toxic effect; Woman; Zidovudine; adverse birth outcomes; adverse outcome; antiretroviral therapy; base; cardiometabolism; case-based; clinical research site; clinically relevant; cohort; comparison group; congenital anomaly; cost effective; design; experience; follow-up; high risk; hospitalization rates; improved; in utero; innovation; interest; large datasets; meetings; mortality; neurodevelopment; perinatal HIV; postnatal; pregnant; prenatal; safety outcomes; success; surveillance study; synergism; transmission process; treatment guidelines; treatment optimization

Project Summary/Abstract The Surveillance Monitoring for ART Toxicities (SMARTT) study was developed by the Pediatric HIV/AIDS Cohort Study (PHACS) network to evaluate the safety of in utero antiretroviral (ARV) exposures on children born to mothers with HIV. The study has been highly productive, informing national and international guidelines for safe and effective ARV regimens during pregnancy. The SMARTT study uses an innovative trigger-based surveillance approach for identifying adverse events (AEs) that may be attributed to prenatal and perinatal ARV therapy exposure. All children receive periodic clinical and laboratory evaluations and only those meeting certain thresholds or “triggers” receive additional assessments to evaluate specific AE criteria designated as “cases”. The study opened to enrollment in 2007, and as of October 2019 has enrolled over 4000 infants and children who are HIV-exposed but uninfected (CHEU) born to mothers with HIV. By 2019, 33% of children had met case status in at least one domain. Pregnant women living with HIV are increasingly receiving combination antiretroviral treatment at the time of conception, and newer ARV medications approved over the last decade have raised concerns regarding possible increased risk of congenital anomalies, preterm birth, and other adverse birth outcomes. As the landscape of treating HIV in pregnancy evolves, there is a need to develop the most cost-effective and informative study designs for future monitoring of ARV safety among CHEU. Building on the established experience of the PHACS network, we will enroll 200 mother-infant pairs over 5 years from 21 clinical sites to evaluate potential adverse birth outcomes and alterations in growth and neurodevelopment, and cardiometabolic, maternal, and oral health based on follow-up from birth through age 5 (intensive follow-up cohort). We will also conduct targeted long-term follow-up through age 17 years among CHEU identified as AE cases based on the SMARTT trigger design, along with a comparison cohort of 800 randomly-selected CHEU (stratified by clinical research site), to evaluate persistence, resolution, and longitudinal profiles of health functioning across multiples domains of interest (extended follow-up cohort). This large cohort will serve as a platform for multiple separately funded emerging research pilots, and allow synergy with other PHACS projects. Innovative epidemiologic and statistical methods will be used to analyze this large dataset to promote improved understanding of both child and maternal health in relation to HIV.

项目概要/摘要 ART 毒性监测 (SMARTT) 研究由儿科开发 HIV/艾滋病队列研究 (PHACS) 网络评估子宫内抗逆转录病毒 (ARV) 暴露的安全性 感染艾滋病毒的母亲所生的孩子。该研究成果丰硕，为国内和国际提供了信息 妊娠期间安全有效的抗逆转录病毒疗法指南。 SMARTT 研究采用创新的 基于触发的监测方法，用于识别可能归因于产前和产后的不良事件 (AE) 围产期抗逆转录病毒治疗暴露。所有儿童都会定期接受临床和实验室评估，并且只有那些 满足某些阈值或“触发点”接受额外评估以评估特定的 AE 标准 指定为“案例”。该研究于 2007 年开始招募，截至 2019 年 10 月，已招募超过 感染艾滋病毒的母亲所生的 4000 名暴露于艾滋病毒但未感染的婴儿和儿童 (CHEU)。到 2019 年， 33% 的儿童至少在一个领域遇到过病例状态。感染艾滋病毒的孕妇越来越多 在受孕时接受联合抗逆转录病毒治疗，并批准更新的抗逆转录病毒药物 在过去的十年中，人们对先天性异常、早产的风险可能增加表示担忧 出生和其他不良出生结果。随着妊娠期艾滋病毒治疗领域的不断发展，出现了一种 需要开发最具成本效益和信息丰富的研究设计，以用于未来 ARV 安全性监测 CHEU 之中。 基于PHACS网络的既定经验，我们将招募200对母婴 历时 5 年，来自 21 个临床中心，评估潜在的不良出生结果以及生长和发育的变化 基于从出生到 5 岁的随访的神经发育、心脏代谢、孕产妇和口腔健康 （密集随访队列）。我们还将进行有针对性的长期随访直至17岁 根据 SMARTT 触发设计确定为 AE 的 CHEU 病例以及比较队列 800 个随机选择的 CHEU（按临床研究地点分层），以评估持久性、分辨率和 跨多个感兴趣领域的健康功能的纵向概况（扩展的随访队列）。这 大型队列将作为多个单独资助的新兴研究试点的平台，并实现协同作用 与其他 PHACS 项目。将使用创新的流行病学和统计方法来分析这一大规模的 数据集，以促进更好地了解与艾滋病毒相关的儿童和孕产妇健康。