The Impact of Alcohol Use on Frontal White Matter in HIV

BACKGROUND: Alcohol use disorder (AUD) is prevalent among individuals diagnosed with human immunodeficiency virus (HIV), and both HIV and alcohol use have been shown to negatively affect the integrity of white matter pathways in the brain. Behavioral, functional, and anatomical impairments have been linked independently to HIV and alcohol use, and these impairments have bases in specific frontally-mediated pathways within the brain. METHODS: Magnetic Resonance Imaging (MRI) data were acquired for 37 HIV+ participants without dementia or hepatitis C. Imaging data were processed through the FreeSurfer and TraCULA pipelines to obtain four bilateral frontal white matter tracts for each participant. Diffusion metrics of white matter integrity along the highest probability pathway for each tract were analyzed with respect to demographics, disease-specific variables, and reported substance use. RESULTS: Significantly increased Axial Diffusivity (AD; decreased axonal integrity) and a trending increase in Mean Diffusivity (MD) were observed along the Anterior Thalamic Radiation (ATR) in participants with a history of AUD. A diagnosis of AUD explained over 36% of the variance in diffusivity along the Anterior Thalamic Radiation overall when accounting for clinical variables including Nadir CD4 and age-adjusted HIV infection length. CONCLUSIONS: The present study provides evidence of HIV-related associations between alcohol use and indicators of axonal integrity loss along the ATR, a frontal pathway involved in the inhibition of addictive or unwanted behaviors. Reduced axonal integrity of this pathway was greatest in HIV+ participants with an AUD, even when considering the effect of age-adjusted disease length and severity (Nadir CD4). This finding implicates a potential biological mechanism linking reduced integrity of frontal white matter to the high prevalence of AUD in an HIV+ population without dementia or hepatitis C.