Serum inflammation markers associated with altered brain white matter microstructure in people with HIV on antiretroviral treatment

Background Many studies have reported reduced brain white matter fractional anisotropy (FA) and increased mean diffusivity (MD) on diffusion tensor imaging (DTI) of people with HIV (PWH). Few, however, have linked individual blood inflammatory markers with white matter tract-specific FA and MD. Methods PWH 50 years old or older from New York, NY, USA, were invited to a cross-sectional study. Demographic data, blood samples, and brain DTI were obtained. Least absolute shrinkage and selection operator (LASSO) regression was used to examine associations between biomarkers and white matter tract-specific FA and MD. All models included age, sex, race, ethnicity, diabetes, hypertension, smoking, and viral load as control variables. Results Seventy-two cases were analyzed. Mean age was 60 ± 6 years, 47% were women, 21% were Hispanic, and 78% were black. All had asymptomatic HIV infection and were on antiretroviral therapy. Eighty-nine percent had CD4 count >200 cell/mm 3 and 78% were virally suppressed. Vascular endothelial growth factor (VEGF) and macrophage inflammatory proteins (MIP) 1β and 1α were consistently associated with lower FA and higher MD across white matter tracts. Conclusions Elevated serum VEGF, MIP-1α, and MIP-1β were associated with altered white matter microstructure. These blood biomarkers may help predict HIV-associated white matter damage.