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

摘要 在全球范围内，未感染艾滋病毒的儿童/青少年人数正在增加， 每年出生的婴儿1.有证据表明，使用高浓度铀的儿童发病率和死亡率增加， 神经认知得分高于未接触HIV的人（HUU）。母公司HOPE研究（NICHD R33103079）旨在比较HEU和HUU儿童的神经发育结局 在纵向队列中从6周龄到3岁，并在多中心交叉队列中评估长期效应， 分段年龄分层队列HOPE研究将评估母体病毒载量、ART时间和 高浓缩铀的结果，并探讨高浓缩铀的神经发育结果是否与 端粒长度（TL）。 行政补充：此补充申请福尔斯属于父母的工作范围 应用程序.母公司赠款的工作范围包括评估影响高浓缩铀/高浓缩铀的辅因子 神经发育结果，包括社会心理、端粒长度和感染性疾病。在这 行政补充提案，我们要求资金用于： ·目标1。描述家庭结构，探讨父母养育（包括父亲养育）的作用， 在HEU和HUU中使用参与性视觉定性研究儿童神经发育结果 方法.定性数据将补充来自1 000个高浓缩铀队列的大量定量数据， 1000 HUU了解照顾者结构如何影响神经发育结果， 一群一群的孩子 ·目标2。进行母体端粒测定（父母预算支持婴儿端粒测定），并使用此 数据，以更好地表征婴儿端粒长度（TL）的辅因子。母体TL测定[已批准 [KNH和UW伦理委员会]是婴儿TL的关键预测因子）。 ·目标3。进行SARS-CoV 2抗体检测[已获得UW人类受试者部批准]， 婴儿干血斑[DBS]已收集在6周和1，2，3岁），以评估产妇的影响 围产期SARS-COV 2对已经测量的纵向婴儿神经发育结果的影响。 这些目标利用了独特的HOPE队列，并能够对关键的 儿童神经发育的决定因素。

Abstract Globally, the number of HIV-exposed uninfected (HEU) children/adolescents is growing, with 1.2 million HEU infants born annually1. There is evidence that HEU children have increased morbidity and mortality, and lower neurocognitive scores than their HIV-unexposed (HUU) counterparts. The parent HOPE study (NICHD R33103079) has been designed to compare neurodevelopmental outcomes between HEU and HUU children from 6-weeks of age to 3 years in a longitudinal cohort and to assess longer term effects in a multi-site cross- sectional age-stratified cohort. The HOPE study will assess influence of maternal viral load, ART timing, and regimen on HEU outcomes, and explore whether HEU neurodevelopmental outcomes are associated with telomere length (TL). Administrative Supplement: This supplement application falls within the scope of work of the parent application. The parent grant scope of work included assessment of cofactors that influence HEU/HUU neurodevelopmental outcomes including psychosocial, telomere length, and infectious diseases. In this Administrative Supplement proposal, we request funding for: • Goal 1. To characterize family structures and explore the roles of parental caregiving (including paternal perspectives) in child neurodevelopmental outcomes in HEU and HUU using participatory visual qualitative methods. Qualitative data will complement extensive quantitative data from the cohort of 1000 HEU and 1000 HUU in understanding how caregiver structure influences neurodevelopmental outcomes in both groups of children. • Goal 2. To conduct maternal telomere assays (parent budget supports infant telomere assays) and use this data to better characterize cofactors of infant telomere length (TL). Maternal TL assays [already approved by KNH and UW ethical committees] are a key predictor of infant TL). • Goal 3. To conduct SARS-CoV2 antibody testing [already approved by UW Human Subjects Division] on infant dried blood spots [DBS] already collected at 6 weeks and 1, 2, 3 years) to assess impact of maternal peripartum SARS-COV2 on already measured longitudinal infant neurodevelopmental outcomes. These goals leverage the unique HOPE cohort and enable more comprehensive assessment of critical determinants of child neurodevelopment.