White matter fiber bundle lengths are shorter in cART naive HIV: an analysis of quantitative diffusion tractography in South Africa

This study examines white matter microstructure using quantitative tractography diffusion magnetic resonance imaging (qtdMRI) in HIV+ individuals from South Africa who were naive or early in the initiation of antiretroviral therapy. Fiber bundle length (FBL) metrics, generated from qtdMRI, for whole brain and six white matter tracts of interest (TOI) were assessed for 135 HIV+ and 21 HIV- individuals. The association between FBL metrics, measures of disease burden, and neuropsychological performance were also investigated. Results indicate significantly reduced sum of whole brain fiber bundle lengths (FBL, p<0.001), but not average whole brain FBL in the HIV+ group compared to the HIV- controls. The HIV+ group exhibited significantly shorter sum of FBL in all six TOIs examined: the anterior thalamic radiation, cingulum bundle, inferior and superior longitudinal fasciculi, inferior frontal occipital fasciculus, and the uncinate fasciculus. Additionally, average FBLs were significantly shorter select TOIs including the inferior longitudinal fasciculus, cingulum bundle, and the anterior thalamic radiation. Shorter whole brain FBL sum metrics were associated with poorer neuropsychological performance, but were not associated with markers of disease burden. Taken together these findings suggest HIV affects white matter architecture primarily through reductions in white matter fiber numbers and, to a lesser degree, the shortening of fibers along a bundle path.