Article

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

University of California, Department of Veterans Affairs Medical Center, San Francisco, CA 94121, USA.
Journal of NeuroVirology (Impact Factor: 3.32). 06/2009; 15(4):324-33. DOI: 10.1080/13550280902973960
Source: PubMed

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.

Full-text

Available from: Dieter Johannes Meyerhoff, Mar 25, 2014
0 Followers
 · 
85 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Combination antiretroviral therapy transformed human immunodefiency virus (HIV)-infection from a terminal illness to a manageable condition, but these patients remain at a significantly elevated risk of developing cognitive impairments and the mechanisms are not understood. Some previous neuroimaging studies have found hyperactivation in frontoparietal networks of HIV-infected patients, whereas others reported aberrations restricted to sensory cortices. In this study, we utilize high-resolution structural and neurophysiological imaging to determine whether alterations in brain structure, function, or both contribute to HIV-related cognitive impairments. HIV-infected adults and individually matched controls completed 3-Tesla structural magnetic resonance imaging (sMRI) and a mechanoreception task during magnetoencephalography (MEG). MEG data were examined using advanced beamforming methods, and sMRI data were analyzed using the latest voxel-based morphometry methods with DARTEL. We found significantly reduced theta responses in the postcentral gyrus and increased alpha activity in the prefrontal cortices of HIV-infected patients compared with controls. Patients also had reduced gray matter volume in the postcentral gyrus, parahippocampal gyrus, and other regions. Importantly, reduced gray matter volume in the left postcentral gyrus was spatially coincident with abnormal MEG responses in HIV-infected patients. Finally, left prefrontal and postcentral gyrus activity was correlated with neuropsychological performance and, when used in conjunction, these two MEG findings had a sensitivity and specificity of over 87.5% for HIV-associated cognitive impairment. This study is the first to demonstrate abnormally increased activity in association cortices with simultaneously decreased activity in sensory areas. These MEG findings had excellent sensitivity and specificity for HIV-associated cognitive impairment, and may hold promise as a potential disease marker. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
    Human Brain Mapping 11/2014; 36(3). DOI:10.1002/hbm.22674 · 6.92 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: HIV-infected individuals frequently exhibit brain dysfunction despite antiretroviral treatment. The neuropathological mechanisms underlying these abnormalities remain unclear, pointing to the importance of identifying biomarkers sensitive to brain dysfunction. We examined 74 medically stable HIV-infected individuals using T1-weighted MRI. Volumes of the cortical grey matter (GM), white matter (WM), caudate, putamen, globus pallidus, thalamus, hippocampus, amygdala, and ventricles were derived using automated parcellation. A panel of plasma cytokines was measured using multiplexed bead array immunoassay. A model selection algorithm was used to select the combination of clinical and cytokine markers that best predicted each brain volumetric measure in a series of linear regression models. Higher CD4 nadir, shorter HIV infection duration, and antiretroviral treatment were significantly related to higher volumes of the putamen, thalamus, hippocampus, and WM. Older age was related to lower volumes in most brain regions and higher ventricular volume. Higher IFN-γ, MCP-1, and TNF-α were related to higher volumes of the putamen, pallidum, amygdala, GM, and WM. Higher IL-1β, IL-6, IL-16, IL-18, IP-10, MIP-1β, and SDF-1α were related to lower volumes of the putamen, pallidum, thalamus, hippocampus, amygdala, GM, and WM; and higher ventricular volume. The current findings provide evidence linking smaller brain volumes to HIV disease history, antiretroviral treatment, and advanced age. Cytokine markers, especially IL-6 and IL-16, showed robust association with brain volumes even after accounting for other clinical variables, demonstrating their utility in examining the mechanisms of HIV-associated brain abnormalities.
    Journal of Neuroimmune Pharmacology 10/2014; 9(5). DOI:10.1007/s11481-014-9567-8 · 3.17 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of this study is to characterize brain gray matter volumetric changes in HIV seropositive without neurocognitive impairment and seronegative men in Asia. We investigate 36 males with HIV seropositive (mean age 34.5±9.1 years) and 33 age- and gender-matched seronegative controls (mean age 31.4±7.6 years) in Asia. The cognitive competence of 36 males with HIV seropositive has no impaired based on performance in the international HIV dementia scale. High-resolution T1-weighted magnetic resonance imaging is performed on a 3.0 T MR system using a standard 32-channel birdcage head coil. Voxel-based morphometry is used to derive volumetric measurements at the level of the individual voxel (p < 0.001, none corrected for multiple comparisons). Compared to the control group, HIV seropositive male lower gray matter volumes are found in left inferior frontal gyrus triangular part and orbital part, left superior temporal gyrus, right middle frontal gyrus and ant cingulum; significant increases gray matter volumes can be seen in Periaqueductal gray and gray around lateral ventricle. HIV infection can change the gray matter volume early without cognitive competence impaired and MR can recognize that changes.
    International Journal of Clinical and Experimental Medicine 01/2014; 7(10):3362-3369. · 1.42 Impact Factor