White Matter Changes in HIV+ Women with a History of Cocaine Dependence

Abstract

Cocaine use is associated with the transmission of human immunodeficiency (HIV) virus through risky sexual behavior. In HIV+ individuals, cocaine use is linked with poor health outcomes, including HIV-medication non-adherence and faster disease progression. Both HIV and cocaine dependence are associated with reduced integrity of cerebral white matter (WM), but the effects of HIV during cocaine abstinence have not yet been explored. We used diffusion tensor imaging (DTI) to understand the effect of combined HIV+ serostatus and former cocaine dependence on cerebral WM integrity. DTI data obtained from 15 HIV+ women with a history of cocaine dependence (COC+/HIV+) and 21 healthy females were included in the analysis. Diffusion-based measures [fractional anisotropy (FA), radial diffusivity (RD), mean diffusivity, and axial diffusivity] were examined using tract-based spatial statistics and region-of-interest analyses. In a whole-brain analysis, COC+/HIV+ women showed significantly reduced FA and increased RD in all major WM tracts, except the left corticospinal tract for RD. The tract with greatest percentage of voxels showing significant between-group differences was the forceps minor (FA: 75.6%, RD: 59.7%). These widespread changes in diffusion measures indicate an extensive neuropathological effect of HIV and former cocaine dependence on WM.

A meta‐analysis of tract‐based spatial statistics studies examining white matter integrity in cocaine use disorder

“…The leave‐one‐out jackknife permutation sensitivity analysis supported the overall pattern of results, with all permutations maintaining statistical significance at the primary threshold. Moreover, all but two permutations supported significance at the exploratory conservative threshold as well (removing the Bell et al 26 or the Wakim et al 27 publications resulted in nonsupported findings at the conservative threshold). Further, although Egger's test of publication bias is problematic for meta‐analyses with fewer than 10 studies, we note that the test did not support publication bias.…”

Structural connectome differences in HIV infection: brain network segregation associated with nadir CD4 cell count

“…More specifically, HIV has been associated with diffuse decreases in FA across projection, association, and commissural WM tracts (Chen et al, 2009; Stubbe-Drager et al, 2012; Su et al, 2016; Wakim et al, 2017). Increased MD has been reported in internal and external capsule fibers and superior cingulate bundles (Pfefferbaum et al, 2009).…”

“…Whole-brain analyses have shown overall decreased FA and increased MD in HIV-positive individuals when compared to HIV-negative controls; these deficits are associated with severity of HIV disease and neurologic dysfunction (Heaps et al, 2011; Ragin et al, 2005; Stubbe-Drager et al, 2012; Su et al, 2016). More specifically, HIV has been associated with diffuse decreases in FA across projection, association, and commissural WM tracts (Chen et al, 2009; Stubbe-Drager et al, 2012; Su et al, 2016; Wakim et al, 2017). Increased MD has been reported in internal and external capsule fibers and superior cingulate bundles (Pfefferbaum et al, 2009).…”

Withaferin A Suppresses Beta Amyloid in APP Expressing Cells: Studies for Tat and Cocaine Associated Neurological Dysfunctions

“…These powerfully addictive stimulant drug molecules have been studied to have an exaggerating effect during HIV infection (Jayant et al, 2017 ). Cocaine (coc), a very common abused drug within PLWH, exerts malicious effects on the CNS (Javadi-Paydar et al, 2017 ; Meade et al, 2017 ; Wakim et al, 2017 ). In the presence of coc, the additive effect of HIV-1 Tat and coc may increase Aβ aggregation, which is a common factor in aging and HIV associated neurological disorders.…”