Evidence for ongoing brain injury in human immunodeficiency virus–positive patients treated with antiretroviral therapy

Abstract

Treatment with antiretroviral therapy (ART) has greatly reduced the incidence of dementia. The goal of this longitudinal study was to determine if there are ongoing macrostructural brain changes in human immunodeficiency virus-positive (HIV+) individuals treated with ART. To quantify brain structure, three-dimensional T1-weighted magnetic resonance imaging (MRI) scans were performed at baseline and again after 24 months in 39 HIV+ patients on ART and 30 HIV− controls. Longitudinal changes in brain volume were measured using tissue segmentation within regions of interest and deformation morphometry. Measured by tissue segmentation, HIV+ patients on ART had significantly (all P < .05) greater rates of white matter volume loss than HIV− control individuals. Compared with controls, the subgroup of HIV+ individuals on ART with viral suppression also had significantly greater rates of white matter volume loss. Deformation morphometry confirmed these results with more specific spatial localization. Deformation morphometry also detected greater rates of gray matter and white matter loss in the subgroup of HIV+ individuals with detectable viral loads. These results provide evidence of ongoing brain volume loss in HIV+ individuals on stable ART, possibly suggesting ongoing cerebral injury. The presence of continuing injury raises the possibility that HIV+ individuals-even in the presence of viral suppression in the periphery-are at greater risk for future cognitive impairments and dementia and possibly faster cognitive decline. Therefore, HIV+ individuals on ART should be monitored for cognitive decline, and treatments that reduce ongoing neurological injury should be considered.

Cognitive function in treated HIV patients

“…In fact, in vivo cognitive impairment has been associated with postmortem neuropathologic changes 60 and with in vivo evidences at magnetic resonance imaging studies of white matter tract injury consistent with axonal or neuronal loss 61 and gray and white matter brain loss. 62 Other potential explanations of persistent cognitive impairment in patients treated with successful HAART include ongoing viral replication of compartmentalized HIV within the CNS 47 and insufficient penetration of some ARV drugs within the CNS. 9 Moreover, ongoing chronic inflammatory processes within the CNS and vascular factors might also contribute to persistent cognitive impairment in patients treated with HAART.…”

The Role of Medical Imaging in Defining CNS Abnormalities Associated with HIV-Infection and Opportunistic Infections

“…One important area of investigation will be the effect of anti-retroviral therapy on the pathologies described above. Studies to date on this issue regularly yield conflicting results [16,25,28,39], and many findings published prior to the HAART (highly active antiretroviral therapy) era have yet to be re-examined in the context of HAART. Additionally, MRI image acquisition and volumetric processing are continually improving, and the use of more sensitive and accurate protocols may confirm or call into question findings of previous studies.…”

A lipid storage–like disorder contributes to cognitive decline in HIV-infected subjects

“…8,9 Despite cART, there is evidence for ongoing neurologic damage that includes persistent astrocyte infection, brain volume loss, inflammation, synaptodendritic damage, and disruptions in white matter integrity. 5,[10][11][12] The mechanisms underlying these residual neuropathologic impairments remain obscure.…”

“…8,9 Despite cART, there is evidence for ongoing neurologic damage that includes persistent astrocyte infection, brain volume loss, inflammation, synaptodendritic damage, and disruptions in white matter integrity. 5,[10][11][12] The mechanisms underlying these residual neuropathologic impairments remain obscure.Several studies have suggested that dysregulations in CNS lipid metabolism may be involved in the pathogenesis of HAND. [13][14][15] In particular, roles for ceramides, sphingomyelins, and cholesterol have been described, but the interrelationships of these bioactive lipids to the temporal progression *These authors contributed equally to this work.…”