Neurodevelopmental Risk in HIV-Exposed Uninfected Children: Call for Developmental Surveillance

As global efforts to prevent mother-to-child transmission of HIV have expanded, the population of children born HIV-exposed, uninfected (HEU) has grown substantially. HEU children face distinctive biological and environmental exposures that may place them at risk for neurodevelopmental challenges. This narrative review synthesizes evidence from the past decade on the neurodevelopmental outcomes of HEU children, including cognitive, motor, and behavioral differences observed across multiple international cohorts. It explores contributing factors such as maternal immune alterations, residual viremia during pregnancy, antiretroviral drug exposure, and postnatal growth impairments. These exposures have been linked to measurable developmental delays in infancy and early childhood, with some effects persisting into school age. Despite these risks, developmental monitoring is not routinely included in the care of HEU children. This review underscores the need to integrate neurodevelopmental surveillance into pediatric HIV-exposed care, optimize anti-retroviral therapy regimens with consideration of fetal outcomes, and support caregiver- and community-based interventions that promote healthy development. Addressing the developmental needs of HEU children is critical to improving long-term outcomes and ensuring this growing population is not left behind.