Sources of Active Brain White Matter Injury in Virally Suppressed HIV Infection Revealed Through Fixel-Based Analysis

To better understand HIV and cardiovascular disease (CVD) effects on brain white matter during HIV infection, advanced diffusion imaging and comprehensive predictor analyses are essential.

Prospective observational cohort study.

84 virally suppressed people with HIV infection (PWH) and 48 uninfected controls underwent T1-weighted, FLAIR, and diffusion MRI at baseline and 24 months later (75 PWH and 40 controls). White Matter Hyperintensity (WMH) volumes were derived from structural scans. Fixel-based analysis tract-based metrics included fibre density (FD), fibre cross-section (FC) and fibre density and cross-section (FDC).

Relative to controls, mixed models showed significant reductions (p<.05 - p<.01) of FC, and lower FDC to a lesser extent, in multiple long cortical association tracts, and within striatal- and thalamic-frontoparietal connections in PWH at both time points. Higher CVD risk was associated with reduced FC in the arcuate fasciculus and FDC in the cingulate gyrus (p<.05). In PWH, more severe cognitive impairment and longer duration of HIV disease was associated with worse FDC across multiple tracts (p<.03 - p<.001). Lower baseline CD4 counts was associated with lower FD in the frontal association tracts (p<.05 - p<.005). Higher WMH volume was associated with higher CVD risk (periventricular p<.001, deep p<.03), but not HIV status.

Major brain white matter tracts are impacted by HIV status, HIV duration, cognitive impairment, baseline CD4, and CVD risk to a lesser extent, despite equal WMH burden between infection groups. Our study provides further evidence of active immuno-vascular underpinning of HIV neuropathogenesis on fine white matter structure despite controlled HIV.