Gray matter asymmetry alterations in perinatally HIV-exposed adolescents: evidence from structural neuroimaging

Perinatal exposure to human immunodeficiency virus (HIV) may disrupt typical neurodevelopment, even without infection. Hemispheric lateralization is a key hallmark of this progress, but it remains poorly characterized in this context. This study investigated gray matter (GM) asymmetry in perinatally HIV-exposed adolescents, both infected and uninfected.

Observational cross-sectional study comparing GM volume and asymmetry across three matched adolescent groups.

Adolescents aged 11-17 years were recruited: adolescents with HIV (AWH, n  = 35), HIV-exposed uninfected (HEU, n  = 70), and typically developing controls (TD, n  = 30). All participants underwent high-resolution 3D T1-weighted MRI. GM volume and asymmetry index (AI) were quantified using voxel-wise analyses, with validation based on homotopic parcellation. Group differences were tested using one-way ANOVA with correction for multiple comparisons.

Significant group effects in GM volume were observed across sensorimotor, visual, frontal, limbic, and cerebellar regions. Both AWH and HEU differed from TD across widespread regions, whereas differences between AWH and HEU were more spatially restricted (precentral gyrus, calcarine sulcus and superior frontal gyrus). For GM asymmetry, ANOVA revealed differences in the amygdala, insula, orbitofrontal cortex, and thalamus. Both AWH and HEU showed notable differences from TD, while differences between AWH and HEU were confined to specific thalamic subregions. Regions of interest (ROI)-wise and meta-analytic validation supported these voxel-wise findings.

Perinatal HIV exposure is associated with atypical GM asymmetry and structural organization in adolescence. Both AWH and HEU exhibit deviations from TD peers, with infection status contributing additional localized alterations.