Persistent neuroimmune alterations in children who are HIV-exposed but uninfected at age 6–7 years: Associations with language development in a South African birth cohort

Background: Children who are HIV-exposed but uninfected (HEU) are at increased risk of neurodevelopmental delays, yet neuroimmune pathways linking perinatal HIV exposure to school readiness remain unclear. Methods: In the Drakenstein Child Health Study, 268 children (94 HEU, 174 HIV-unexposed [HU]) underwent magnetic resonance spectroscopy in midline parietal grey and left parietal white matter regions at 6-7 years. Peripheral blood serum immune markers were measured in pregnancy and in children at 6 weeks, 2, 3, and 5 years. Linear mixed-effects models characterised child immune trajectories and linear regressions tested associations with creatine-referenced neurometabolite ratios and school readiness scores. Results: Mothers living with HIV had higher sCD14 and lower MMP-9, NGAL, and GM-CSF than mothers without HIV (p