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; 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 针对艺术毒性的监视监测（SMARTT）研究是由小儿开发的 艾滋病毒/艾滋病队列研究（PHACS）网络评估子宫抗逆转录病毒（ARV）的安全性 艾滋病毒母亲出生的孩子。这项研究的生产力很高，通知了国家和国际 怀孕期间安全有效的ARV方案指南。 Smartt研究使用了创新 基于触发的监视方法，用于识别可能归因于产前和的广告事件（AES） 围产期ARV治疗暴露。所有儿童都会接受定期临床和实验室评估，只有 达到某些阈值或“触发器”会获得其他评估以评估特定AE标准 被指定为“案例”。这项研究于2007年开始入学，从2019年10月开始 艾滋病毒母亲出生的4000名艾滋病毒暴露但未感染的婴儿和未感染的儿童。到2019年， 33％的儿童在至少一个领域达到了案件状态。感染艾滋病毒的孕妇越来越多 在概念时接受组合抗逆转录病毒治疗，并批准了更新的ARV药物 在过去的十年中 生日和其他不利的生日成果。作为治疗艾滋病毒妊娠进化的景观，有一个 需要开发最具成本效益和信息丰富的研究设计，以使ARV安全的未来监控 在Cheu中。 在PHACS网络的既定经验的基础上，我们将注册200对母 从21个临床部位开始超过5年，以评估潜在的不良出生结果和增长的改变和改变 基于从出生到5岁的随访，神经发育以及心脏代谢，母体和口腔健康 （密集的后续队列）。我们还将在17岁之前进行针对性的长期随访 在基于Smartt Trigger设计的AE案件的CHEU中，以及比较队列 800个随机选择的CHEU（由临床研究地点分层），以评估持久性，解决方案和 跨多个感兴趣领域的健康功能的纵向谱（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飞行员的平台，并允许协同作用 与其他PHAC项目。创新的流行病学和统计方法将用于分析这一大型 数据集以促进与艾滋病毒有关的儿童和孕产妇健康的了解。