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Browsing by Author "Navia, Bradford"
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Item Patterns of White Matter Injury in HIV Infection after Partial Immune Reconstitution: A DTI Tract-Based Spatial Statistics Study(Springer, 2013) Zhu, Tong; Zhong, Jianhui; Hu, Rui; Tivarus, Madalina; Ekholm, Sven; Harezlak, Jaroslaw; Ombao, Hernando; Navia, Bradford; Cohen, Ron; Schifitto, Giovanni; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public HealthHIV-infected individuals with severe immune suppression are more likely to develop HIV-associated neurocognitive disorders than those with preserved immune function. While partial immune reconstitution occurs in those with severe immune suppression after starting combined antiretroviral therapy, it is not established whether improvement in immune function reverses or prevents injury to the central nervous system (CNS). To address this question, 50 participants (nadir CD4 counts ≤ 200 cells/mm(3), on a stable antiretroviral regimen for at least 12 consecutive weeks prior to study) and 13 HIV negative participants underwent a comprehensive neurological evaluation followed by diffusion tensor imaging (DTI). Eighty-four percent of the 50 HIV participants were neurologically asymptomatic (HIVNA) and 16 % had mild cognitive impairment (HIVCI). Tract-based spatial statistics (TBSS) on DTI data revealed that mean diffusivity (MD) increased significantly in the posterior aspect of both hemispheres in HIVNA compared to controls. In HIVCI, compared to controls and HIVNA, increased MD extended to prefrontal areas. Fractional anisotropy decreased only in HIVCI, compared to either controls or HIVNA. Furthermore, DTI showed significant correlations to duration of HIV infection and significant associations with multiple cognitive domains. This study highlights that in partial immune reconstitution, injury to the CNS is present even in those that are neurologically asymptomatic and there are discrete spatial patterns of white matter injury in HIVNA subjects compared to HIVCI subjects. Our results also show that quantitative analysis of DTI using TBSS is a sensitive approach to evaluate HIV-associated white matter disease and thus valuable in monitoring central nervous system injury.Item Regional areas and widths of the midsagittal corpus callosum among HIV-infected patients on stable antiretroviral therapies(Springer US, 2011-08) Tate, David F.; Sampat, Mehul; Harezlak, Jaroslaw; Fiecas, Mark; Hogan, Joseph; Dewey, Jeffrey; McCaffrey, Daniel; Branson, Daniel; Russell, Troy; Conley, Jared; Taylor, Michael; Schifitto, Giavoni; Zhong, J.; Daar, Eric S.; Alger, Jeffrey; Brown, Mark; Singer, Elyse; Campbell, T.; McMahon, D.; Tso, Y.; Matesan, Janetta; Letendre, Scott; Paulose, S.; Gaugh, Michelle; Tripoli, C.; Yiannoutsos, Constantine; Bigler, Erin D.; Cohen, Ronald A.; Guttmann, Charles R. G.; Navia, Bradford; HIV Neuroimaging Consortium; Department of Biostatistics, Richard M. Fairbanks School of Public HealthRecent reports suggest that a growing number of human immunodeficiency virus (HIV)-infected persons show signs of persistent cognitive impairment even in the context of combination antiretroviral therapies (cART). The basis for this finding remains poorly understood as there are only a limited number of studies examining the relationship between CNS injury, measures of disease severity, and cognitive function in the setting of stable disease. This study examined the effects of HIV infection on cerebral white matter using quantitative morphometry of the midsagittal corpus callosum (CC) in 216 chronically infected participants from the multisite HIV Neuroimaging Consortium study currently receiving cART and 139 controls. All participants underwent MRI assessment, and HIV-infected subjects also underwent measures of cognitive function and disease severity. The midsagittal slice of the CC was quantified using two semi-automated procedures. Group comparisons were accomplished using ANOVA, and the relationship between CC morphometry and clinical covariates (current CD4, nadir CD4, plasma and CSF HIV RNA, duration of HIV infection, age, and ADC stage) was assessed using linear regression models. HIV-infected patients showed significant reductions in both the area and linear widths for several regions of the CC. Significant relationships were found with ADC stage and nadir CD4 cell count, but no other clinical variables. Despite effective treatment, significant and possibly irreversible structural loss of the white matter persists in the setting of chronic HIV disease. A history of advanced immune suppression is a strong predictor of this complication and suggests that antiretroviral intervention at earlier stages of infection may be warranted.