Topographies of Cortical and Subcortical Volume Loss in HIV and Aging in the cART Era

Objectives: Studies of HIV-associated brain atrophy often focus on a priori brain regions of interest, which can introduce bias. A data-driven, minimally biased approach was used to analyze changes in brain volumetrics associated with HIV and their relationship to aging, viral factors, combination antiretroviral therapy (cART), and gender, and smoking. Design: A cross-sectional study of 51 HIV-uninfected (HIV2) and 146 HIV-infected (HIV+) participants. Methods: Structural MRI of participants was analyzed using principal component analysis (PCA) to reduce dimensionality and determine topographies of volumetric changes. Neuropsychological (NP) assessment was examined using global and domain-specific scores. The effects of HIV disease factors (eg, viral load, CD4, etc.) on brain volumes and neuropsychological were investigated using penalized regression (LASSO). Results: Two components of interest were visualized using principal component analysis. An aging effect predominated for both components. The first component, a cortically weighted topography, accounted for a majority of variance across participants (43.5% of variance) and showed independent effects of HIV and smoking. A secondary, subcortically weighted topography (4.6%) showed HIV-status accentuated age-related volume loss. In HIV+ patients, the cortical topography correlated with global neuropsychological scores and nadir CD4, whereas subcortical volume loss was associated with recent viral load. Conclusions: Cortical regions showed the most prominent volumetric changes because of aging and HIV. Within HIV+ participants, cortical volumes were associated with immune history, whereas subcortical changes correlated with current immune function. Cognitive function was primarily associated with cortical volume changes. Observed volumetric changes in chronic HIV+ patients may reflect both past infection history and current viral status.