Surveillance Monitoring for ART Toxicities (SMARTT) Study

ART 毒性监测 (SMARTT) 研究

• 批准号: 10264952
• 负责人: PAIGE L WILLIAMS
• 金额: $ 10.21万
• 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/10264952
• 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; Treatment-related toxicity; 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; 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.

项目总结/摘要 ART毒性监测（SMARTT）研究由儿科开发 艾滋病毒/艾滋病队列研究（PHACS）网络，以评估子宫内抗逆转录病毒（ARV）暴露对 艾滋病毒携带者母亲所生的儿童。这项研究成果丰硕，为国家和国际社会提供了信息， 怀孕期间安全有效的抗逆转录病毒治疗指南。SMARTT研究采用了一种创新的 用于识别可能归因于产前和产后疾病的不良事件（AE）的基于患者的监测方法 围产期抗逆转录病毒治疗暴露。所有儿童都接受定期的临床和实验室评估，只有那些 满足某些阈值或“触发因素”的患者接受额外评估，以评价特定AE标准 称为“案件”。该研究于2007年开始招募，截至2019年10月，已招募了超过 4 000名艾滋病毒感染母亲所生的艾滋病毒暴露但未感染的婴儿和儿童。到2019年， 33%的儿童在至少一个领域符合病例状态。感染艾滋病毒的孕妇越来越多 在受孕时接受抗逆转录病毒联合治疗，并批准了新的抗逆转录病毒药物 在过去的十年中，已经引起了对先天性异常、早产 分娩和其他不良的分娩结果。随着妊娠期艾滋病治疗的发展， 需要为未来的抗逆转录病毒药物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CHEU之间。 根据PHACS网络的既定经验，我们将招募200对母婴 来自21个临床研究中心的5年以上的研究，以评估潜在的不良出生结局和生长变化， 神经发育、心脏代谢、孕产妇和口腔健康，基于从出生到5岁的随访 （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病例的CHEU中，沿着的是比较队列 800例随机选择的CHEU（按临床研究中心分层），以评价持久性、消退和 跨多个关注领域的健康功能纵向概况（扩展随访队列）。这 一个大的队列将作为多个单独资助的新兴研究试点的平台，并允许协同作用 其他PHACS项目。创新的流行病学和统计方法将被用来分析这一大规模的 数据集，以促进更好地了解儿童和孕产妇健康与艾滋病毒的关系。