HEU outcomes: population-evaluation and screening strategies (HOPE)

HEU 结果：人群评估和筛查策略 (HOPE)

• 批准号: 10645291
• 负责人: Grace John-Stewart
• 金额: $ 66.35万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-07 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10645291
• 关键词: Adolescence; Adolescent; Adult; Adult Children; Affect; Africa South of the Sahara; Age; Anti-Retroviral Agents; Anxiety; Assessment tool; Attention deficit hyperactivity disorder; Biological Markers; Blood; Brain imaging; Caring; Child; Clinic; Clinical Data; Cognitive; Collaborations; Communities; Complement; Computerized Medical Record; Cost Analysis; Data; Depression and Suicide; Development; Diagnostic; Early Intervention; Educational workshop; Enrollment; Epidemiology; Evaluation; Exposure to; Future; General Population; Growth; Guidelines; HIV; HIV antiretroviral; HIV-exposed uninfected infant; Health; Hearing; Income; Individual; Infant; Infection; Inflammation; Intervention; Kenya; Length; Link; Longitudinal Studies; Longitudinal cohort; Medical; Medical Records; Mental Depression; Mental Health; Monitor; Morbidity - disease rate; Mother-to-child HIV transmission; Mothers; Neurodevelopmental Deficit; Outcome; Performance; Perinatal; Persons; Pharmaceutical Preparations; Phase; Policies; Population; Pregnancy; Prevention; Public Health; Regimen; Risk; Sampling Studies; Screening procedure; Site; Spottings; Surveys; System; Treatment Protocols; Viral Load result; Woman; Work; adverse outcome; aged; autism spectrum disorder; base; clinically relevant; cofactor; cohort; cost estimate; design; diagnostic tool; efavirenz; epidemiology study; experience; fetal; follow-up; health assessment; imaging study; infancy; insight; mortality; neurodevelopment; novel strategies; open source; pilot test; population based; prenatal exposure; prevent; programs; recruit; rural setting; screening; screening program; telomere; tool; treatment guidelines; urban setting

ABSTRACT There is a substantial and growing population of children/adolescents who are HIV exposed uninfected (HEU) in sub-Saharan Africa (SSA). There is emerging evidence that fetal exposure to maternal infections and medications may result in adverse adult/adolescent mental health outcomes; it is plausible that fetal exposure to HIV or antiretrovirals (ART) could similarly influence long-term outcomes. Despite evidence for poor growth and neurodevelopmental deficits, programs to systematically monitor neurodevelopmental and mental health outcomes among HEU at a population level are lacking. Understanding whether there are increased adverse neurodevelopmental and mental health outcomes in HEU due to fetal HIV/ART exposure has been challenged by difficulties in defining appropriate comparator cohorts, changing PMTCT treatment guidelines, and lack of validated, scale-able assessment tools. Our team has a unique track record for moving novel approaches for screening and testing from pilot to implementation, conducting large scale evaluations, and conducting neurodevelopmental and mental health assessments in HIV-affected children and adolescents. We propose parallel longitudinal and population based HEU/HUU cohorts, in urban and rural settings, spanning infants/children/adolescents age 6 weeks to 18 years to determine differences in neurodevelopmental and mental health outcomes. The R61 phase will accrue a longitudinal homogenous cohort of 2000 HEU/HUU infants exposed to Option B+ PMTCT treatment regimens, with extended follow-up in the R33 phase for a total of for 4 years, and assessed for neurodevelopmental, mental health, hearing, growth outcomes and telomere length. An approach to survey older HEU/HUU (age 3-18) for neurodevelopmental and mental health outcomes and collect maternal medical, ART regimen and timing, and viral load data from medical records will be piloted in the R61 phase and expanded to 100 HIV clinics in the R33 phase. Selected neurodevelopmental/mental health screening and diagnostic tools to be used are based on open source availability, diagnostic or screening performance, cultural appropriateness, accessibility, and clinical relevance. In the national R33 survey, cost analysis will complement clinical data; and together, will be disseminated to stakeholders at a workshop to develop a framework for an integrated HEU screening program in public health settings. This proposal leverages extensive team experience in prior longitudinal MTCT cohorts, in national child and adolescent surveys, HEU recruitment, neurodevelopmental and mental health assessment, and medical record extraction and analysis at scale, to comprehensively understand burden, mechanism and outcomes in HEU. Engaging stakeholders has the potential to enhance HEU management programmatically based on findings.

抽象的 有大量未感染艾滋病毒的儿童/青少年 (HEU)，而且数量还在不断增加 撒哈拉以南非洲 (SSA)。越来越多的证据表明，胎儿接触母体感染和 药物可能会导致成人/青少年心理健康不良结果；胎儿暴露于 HIV 或抗逆转录病毒药物 (ART) 可能同样影响长期结果。尽管有证据表明增长不佳 和神经发育缺陷，系统监测神经发育和心理的计划 HEU 在人口层面上的健康结果缺乏。了解是否增加 胎儿 HIV/ART 暴露导致 HEU 神经发育和心理健康不良结果已被证实 面临着难以确定适当的比较队列、改变预防母婴传播治疗指南的挑战，以及 缺乏经过验证的、可扩展的评估工具。 我们的团队在将筛选和测试的新颖方法从试点转移到 实施、进行大规模评估以及进行神经发育和心理健康 对受艾滋病毒影响的儿童和青少年进行评估。我们提出平行纵向和总体 基于 HEU/HUU 队列，在城市和农村环境中，涵盖 6 周龄的婴儿/儿童/青少年 至 18 岁，以确定神经发育和心理健康结果的差异。 R61相 将产生一个由 2000 名接受选项 B+ PMTCT 治疗的 HEU/HUU 婴儿组成的纵向同质队列 方案，在 R33 阶段进行总共 4 年的延长随访，并评估 神经发育、心理健康、听力、生长结果和端粒长度。调查老年人的方法 HEU/HUU（3-18 岁）用于神经发育和心理健康结果并收集孕产妇医疗、ART 治疗方案和时间安排以及病历中的病毒载量数据将在 R61 阶段进行试点，并扩展到 R33 阶段有 100 个 HIV 诊所。精选的神经发育/心理健康筛查和诊断工具 使用基于开源可用性、诊断或筛查性能、文化适宜性、 可及性和临床相关性。在国家R33调查中，成本分析将补充临床数据；和 将在研讨会上向利益相关者传播，以制定综合高浓铀框架 公共卫生机构的筛查计划。 该提案利用了先前纵向 MTCT 队列、全国儿童和儿童群体中的丰富团队经验。 青少年调查、HEU 招募、神经发育和心理健康评估以及医疗记录 大规模提取和分析，全面了解高浓铀的负担、机制和结果。 利益相关者的参与有可能根据调查结果有计划地加强高浓铀管理。