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

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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.