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, and combination antiretroviral therapy (cART), as well as gender and smoking. DESIGN:A cross-sectional study of 51 HIV-uninfected (HIV–) 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 (e.g. viral load, CD4, etc.) on brain volumes and NP were investigated using penalized regression (LASSO). RESULTS:Two components of interest were visualized using PCA. 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 as well as 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 NP scores and nadir CD4, while subcortical volume loss was associated with recent viral load. CONCLUSIONS:Cortical regions showed the most prominent volumetric changes due to aging and HIV. Within HIV+ participants, cortical volumes were associated with immune history while 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.