Background and PurposeThere are an estimated 1.5 million children living with HIV (CLHIV), most residing in sub-Saharan Africa. A common hospital presentation of CLHIV is the occurrence of seizure, for which imaging is helpful but is not routinely performed due to scarce resources. We present imaging findings and their association with clinical risk factors and outcomes in a cohort of Zambian CLHIV presenting with new-onset seizure. MethodsIn this prospective cohort study, participants were recruited at the University Teaching Hospital (UTH) in Lusaka, Zambia. Various clinical and demographic characteristics were obtained. Either CT or MRI, or both, were obtained during admission or shortly after discharge. If both studies were available, MRI data was used. Two neuroradiologists interpreted images using REDCap-based NeuroInterp, a tool which quantifies brain imaging findings. Age-dependent neuropsychological assessments were administered. Results19/39 (49%) children had a brain MRI, 16/39 (41%) had CT and 4/39 (10%) had both. Mean age was 6.8 years (SD = 4.8). Children with advanced HIV disease had higher odds of atrophy (OR 7.2 95% CI 1.1 to 48.3). Focal abnormalities were less likely in children receiving ART (OR 0.22 95% CI 0.05 to 1.0). Children with neurocognitive impairment were more likely to have atrophy (OR 8.4 95% CI 1.3 to 55.4) and less likely to have focal abnormalities (OR 0.2 95% CI 0.03 to 0.9). ConclusionFocal brain abnormalities on MRI were less likely in CLHIV on ART. Brain atrophy was the most common imaging abnormality, which was linked to severe neurocognitive impairment.