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

摘要 有大量且不断增长的儿童/青少年未感染艾滋病毒(HEU) 在撒哈拉以南非洲(SSA)。有新的证据表明，胎儿接触母体感染和 药物可能会导致成人/青少年的不良心理健康结果；胎儿暴露在 艾滋病毒或抗逆转录病毒药物(ART)同样会影响长期结果。尽管有证据表明增长不佳 和神经发育缺陷，系统地监测神经发育和智力的计划 在人口层面上，高浓缩铀的健康结果是缺乏的。了解是否有增加的 由胎儿HIV/ART暴露引起的HEU的不良神经发育和心理健康后果一直是 在确定适当的对照队列、改变防止母婴传播治疗指南方面遇到困难，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方法从试点转移到 实施，进行大规模评估，并开展神经发育和心理健康 对感染艾滋病毒的儿童和青少年的评估。我们提出并行的纵向和总体 以HEU/HUU为基础的队列，在城市和农村环境中，跨越6周大的婴儿/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阶段 接受选择B母婴传播治疗的2000名HEU/HUU婴儿的纵向同质性队列 方案，在R33阶段延长随访，共4年，并评估为 神经发育、心理健康、听力、生长结果和端粒长度。一种调查老年人的方法 HEU/HUU(3-18岁)关于神经发育和心理健康结果的调查，并收集孕产妇医学，ART 方案和时间，以及来自医疗记录的病毒载量数据将在R61阶段试行，并扩大到 100家艾滋病毒诊所处于R33期。精选的神经发育/心理健康筛查和诊断工具 基于开放源码可用性、诊断或筛查性能、文化适当性、 可及性和临床相关性。在全国R33调查中，成本分析将补充临床数据；以及 将在一次研讨会上一起向利益攸关方传播，以制定一个综合高浓缩铀框架 公共卫生环境中的筛查计划。 这项建议利用了在以前的纵向MTCT队列中的丰富团队经验，在国家儿童和 青少年调查、HEU招募、神经发育和精神健康评估以及医疗记录 在规模上提取和分析，全面了解高浓缩铀的负担、机制和结果。 利益攸关方的参与有可能在调查结果的基础上以方案方式加强高浓缩铀管理。

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.