IMAGE: Neuroimaging to Investigate Brain Development in Children after Exposure to HIV and or Antiretrovirals

There is a growing number of children exposed to HIV who remain uninfected (CHEU) and increasing likelihood of antiretroviral (ARV) use in pregnancy for either HIV treatment or prevention. Even a small impact of HIV or ARV exposure on CHEU would have a large population-level effect in countries like Botswana, where 20% of children are HEU. Drivers of neurodevelopmental differences observed among CHEU remain unclear. Neuroimaging can assess neurobiological differences in children with differing HIV and ARV exposures. MRI studies of young CHEU suggest structural brain differences compared to children without HIV exposure (CHU), associated with functional outcomes like language. Yet, no longitudinal neuroimaging studies of CHEU map brain development trajectories through older childhood into adolescence, despite ongoing brain growth, and data from the era of dolutegravir (DTG) do not exist to date. Large, multi-country evaluations are especially needed as population-level standard distributions of brain metrics and neurodevelopment scores are not yet defined. Our proposal addresses key knowledge gaps by defining brain maturation of CHEU into adolescence for the first time in a large multi-country cohort, identifying pathways for developmental differences (e.g., ARV, HIV exposure), and clarifying the impact of neurobiological alterations among CHEU using novel MRI approaches that are now accessible in HIV priority settings. We propose a significant advancement to our prior work—a well- powered, prospective, multi-country, neuroimaging and neurodevelopment evaluation that leverages ongoing CHEU cohorts in Botswana and Kenya with exposure to various ART regimens (e.g., EFV, TDF, DTG), children who have only ARV exposure (PrEP), and children without HIV or ARV exposure. Our proposal is designed to examine brain development in HIV priority settings and will create pediatric HIV neuroimaging repository in a combined cohort to unravel neurobiological pathways following ARV/HIV exposure. We will extend follow up to 10 years with annual neuroimaging on all children (3 timepoints per child) to characterize brain metrics following ARV and/or HIV exposure (Aim 1). We will also test the hypothesis that smaller brain volumes are associated with poorer neurodevelopment in late childhood, especially in CHEU, by rigorously conducting standardized assessments across domains (attention/executive function, learning and memory, complex cognition, sensorimotor function, and processing speed) and testing whether domain scores differ by HIV and/or ARV exposure (Aim 2). Finally, we will examine if brain metrics are associated with school performance and neurocognition in adolescents who are HEU (Aim 3). Project 1 synergizes with the other U19 Projects by examining neurobiological factors that influence development. Project 1 will provide a large repository of pediatric neuroimaging data for future research, including neurobiological outcomes of other infectious diseases (e.g., malaria) and maternal exposures. Project Number: 1U19HD118601-01 | Fiscal Year: 2025 | NIH Institute/Center: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | Principal Investigator: Jillian Pintye | Institution: UNIVERSITY OF WASHINGTON, SEATTLE, WA | Award Amount: $559,276 | Activity Code: U19 | Study Section: Special Emphasis Panel[ZHD1 DSR-B (50)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11145406