Clinical contributors to cerebral white matter integrity in HIV-infected individuals

Abstract

HIV-infected people frequently exhibit brain dysfunction characterized by preferential damage to the cerebral white matter. Despite suppressed viral load and reconstituted immune function afforded by combination antiretroviral therapy (CART), brain dysfunction continues to be observed even in medically stable individuals. To provide insight into the etiology of HIV-associated brain dysfunction in the CART era, we examined the effects of HIV disease markers, antiretroviral treatment, hepatitis C (HCV) coinfection, and age on DTI measures of white matter integrity in a cohort of 85 individuals aged 23 to 65 with chronic HIV infection. Fractional anisotropy (FA) and mean diffusivity (MD) were derived from 29 cerebral white matter regions, which were segmented on each individual brain using a high-resolution T1-weighted image and registered to diffusion images. Significant effects of clinical variables were found on white matter abnormalities in nearly all brain regions examined. Most notably, HCV coinfection and older age were associated with decreased anisotropy or increased diffusivity in the majority of brain regions. Individuals with higher current CD4 levels exhibited higher anisotropy in parietal lobe regions, while those undergoing antiretroviral treatment exhibited higher anisotropy in temporal lobe regions. The observed diffuse pattern of white matter injury suggests that future neuroimaging studies should employ methodologies that are not limited to circumscribed regions of interest. The current findings underline the multifactorial nature of HIV-associated brain dysfunction in the CART era, and the importance of examining the effect of HIV disease in the context of other comorbidities, in particular HCV coinfection and aging.

White matter measures are near normal in controlled HIV infection except in those with cognitive impairment and longer HIV duration

“…resulted in inconsistent results. Moreover, variations in the studied HIV+ participants in relation to their combination antiretroviral (cART) status, level of viral suppression, the nature of HIV disease , and their demographics (mainly age) (Towgood et al 2012;Chang et al 2008;Gongvatana et al 2011;Seider et al 2015) have probably contributed to a lack of consistency. Altogether, while DTI may be useful at characterizing the extent of WM injury in cases with moderate to severe HIV-associated neurocognitive disorder (HAND) (Chang et al 2008;Chen et al 2009;Gongvatana et al 2011) or advanced untreated HIV infection (Hoare et al 2011;Leite et al 2013;Pfefferbaum et al 2009) (when HIV replication is the cause of the WM damage), its use at elucidating what may be the HIV-related neuropathology substrate in virally suppressed HIV infection is less clear.…”

Disrupted Brain Networks in the Aging HIV+ Population

“…The volume of the supramarginal gyrus declines in ApoE4 carriers as they convert from mild cognitive impairment to AD (Spampinato et al, 2011). In a diffusion-based study, the regions underlying the gyrus showed suggestive negative associations between FA and age in HIV patients (Gongvatana et al, 2011). Brown et al (2011) also found a significant genetic effect in the supramarginal gyrus.…”

An Overview of Human Immunodeficiency Virus Type 1-Associated Common Neurological Complications: Does Aging Pose a Challenge?

“…On the other hand, HIV-negative and early HIV-infected (≤1 year of viral exposure) patients exhibit only disruption of the BBB and no significant alterations in WM integrity [248]. Moreover, aging HIV-infected patients exhibit greater WM hyper-intensities and lower fractional anisotropy in the anterior corona radiata due to hepatitis C virus coinfection, the more likely development of AIDS, and higher CD4-positive cell counts as a marker of hyper-activation of inflammatory responses [245, 249]. …”