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

摘要 有大量儿童/青少年暴露于艾滋病毒而未受感染，而且人数在不断增加。 在撒哈拉以南非洲（SSA）。有新的证据表明，胎儿暴露于母体感染， 药物可能导致不良的成人/青少年心理健康结果;胎儿暴露于 艾滋病毒或抗逆转录病毒药物（ART）也可能同样影响长期结果。尽管有证据表明增长乏力 和神经发育缺陷，系统监测神经发育和精神 在人口一级，缺乏高浓缩铀的健康结果。了解是否有增加 由于胎儿接触艾滋病毒/抗逆转录病毒疗法， 由于难以定义适当的对照队列，改变PMTCT治疗指南， 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推广到 实施，进行大规模评估，并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。我们建议平行纵向和人口 城市和农村地区6周大的婴儿/儿童/青少年 到18岁，以确定神经发育和心理健康结果的差异。R61阶段 将累积2000名接受选项B+预防母婴传播治疗的高浓缩铀/高浓缩铀婴儿的纵向同质队列 方案，在R33期延长随访，共4年，并评估 神经发育、心理健康、听力、生长结果和端粒长度。老年人调查方法 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、抗逆转录病毒疗法 方案和时间，以及来自病历的病毒载量数据将在R61阶段进行试点，并扩大到 R33阶段的100个艾滋病毒诊所。选定的神经发育/心理健康筛查和诊断工具， 基于开源可用性、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; 将在一个讲习班上向利益攸关方散发，以制定一个综合高浓缩铀框架 公共卫生机构的筛查计划。 该提案利用了团队在先前纵向母婴传播队列、国家儿童和 青少年调查、高浓缩铀招募、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，全面了解高浓缩铀的负担、机制和结果。 让利益攸关方参与，有可能根据调查结果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.