Structural brain abnormalities in successfully treated HIV infection: associations with disease and cerebrospinal fluid biomarkers.

Abstract

Background: Brain structural abnormalities have been reported in persons with HIV (PWH) on suppressive combination antiretroviral therapy (cART), but their pathophysiology remains unclear. Methods: We investigated factors associated with brain tissue volumes and white matter microstructure (fractional anisotropy) in 134 PWH on suppressive cART and 79 comparable HIV-negative controls, aged ≥45 years from the Co-morBidity in Relation to AIDS (COBRA) cohort, using multimodal neuroimaging and cerebrospinal fluid (CSF) biomarkers. Results: Compared to controls, PWH had lower grey matter volumes (-13.7 mL [95%-confidence interval -25.1, -2.2 mL]) and fractional anisotropy (-0.0073 [-0.012, -0.0024]), with the largest differences observed in those with prior clinical AIDS. Hypertension and CSF soluble CD14 concentration were associated with lower fractional anisotropy. These associations were independent of HIV serostatus (Pinteraction=0.32 and Pinteraction=0.59, respectively) and did not explain the greater abnormalities in brain structure in relation to HIV. Conclusions: The presence of lower grey matter volumes and more white matter microstructural abnormalities in well-treated PWH partly reflect a combination of historical effects of AIDS, as well as the more general influence of systemic factors such as hypertension and ongoing neuroinflammation. Additional mechanisms explaining the accentuation of brain structure abnormalities in treated HIV infection remain to be identified.