Surveillance Monitoring for ART Toxicities (SMARTT) Study

ART 毒性监测 (SMARTT) 研究

• 批准号: 10663919
• 负责人: PAIGE L WILLIAMS
• 金额: $ 9.98万
• 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/10663919
• 关键词: 17 year old; 5 year old; Adult; Adverse effects; Adverse event; Age; Anti-Retroviral Agents; Birth; Child; Child Health; Clinical; Clinical stratification; Conceptions; Databases; Enrollment; Epidemiologic Methods; Evaluation; Funding; Future; Goals; Growth; Guidelines; HIV; Health; Hearing; Infant; Infant Health; Infection; Insulin Resistance; International; International Maternal Pediatric Adolescent AIDS Clinical Trials; Investigation; Laboratories; Language; Lipids; Longterm Follow-up; Maternal Health; Metabolic; Monitor; Mothers; Oral health; Outcome; Pediatric HIV/AIDS Cohort Study; Perinatal; Periodicals; Pharmaceutical Preparations; Pregnancy; Pregnant Women; Premature Birth; Prevention; Productivity; Public Health; Random Allocation; Recommendation; Regimen; Reporting; Research; Research Design; Resolution; Risk; Safety; Statistical Methods; Suggestion; System; Tenofovir; Time; Toxic effect; Treatment-related toxicity; Woman; Zidovudine; adverse birth outcomes; adverse outcome; antiretroviral therapy; 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; maternal safety; 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.

项目摘要/摘要 ART毒性监测(SMARTT)研究是由儿科 HIV/AIDS队列研究(PHACS)网络评估宫内抗逆转录病毒(ARV)暴露的安全性 艾滋病毒携带者母亲所生的孩子。这项研究卓有成效，为国内和国际提供了信息 怀孕期间安全有效的抗逆转录病毒疗法指南。Smartt的研究使用了一种创新的 基于触发的监测方法，用于识别可能归因于产前和 围产期抗逆转录病毒治疗暴露。所有儿童都会接受定期的临床和实验室评估，只有 达到某些阈值或“触发因素”会收到额外的评估，以评估特定的AE标准 指定为“个案”。该研究于2007年开始招生，截至2019年10月，已有超过 4,000名感染艾滋病毒但未感染的婴儿和儿童(CHEU)，其母亲感染艾滋病毒。到2019年， 33%的儿童至少在一个领域达到了病例状态。携带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，并批准新的抗逆转录病毒药物 在过去的十年中提出了对可能增加的先天异常风险的担忧，早产 分娩，以及其他不利的分娩后果。随着妊娠期间治疗艾滋病毒的格局的演变，有一种 需要为未来的抗逆转录病毒安全性监测开发最具成本效益和信息量最大的研究设计 在Chu中。 根据PHACS网络的既定经验，我们将招收200对母婴 从21个临床地点进行5年以上的评估，以评估潜在的不良分娩结局和生长发育和 神经发育，心脏代谢，母亲和口腔健康，基于从出生到5岁的跟踪调查 (密集跟踪队列)。我们还将进行有针对性的长期随访，直至17岁 在根据Smartt触发器设计确定为AE病例的CHEU中，以及比较队列 随机选择的800个CHEU(按临床研究站点分层)，以评估持久性、分辨率和 多个感兴趣领域的卫生功能的纵向概况(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，并允许协同 与其他PHACS项目合作。创新的流行病学和统计学方法将被用来分析这个大的 数据集，以促进更好地了解儿童和产妇健康与艾滋病毒的关系。