Increasing CD4 levels are associated with more white matter abnormalities and increased gray matter over time in HIV: The CHARTER Study.

Type: Poster
Title: Increasing CD4 levels are associated with more white matter abnormalities and increased gray matter over time in HIV: The CHARTER Study.
Authors: Fennema-Notestine C, Archibald SL, Notestine RJ, TaylorMJ, Theilmann RJ, Julaton M, Letendre SL, Ellis RJ, Heaton RK, Gamst AC, Franklin, Jr. DR, Clifford DB, Collier AC, Gelman BB, Marra C, McArthur JC, McCutchan JA, Morgello S, Simpson DM, Grant I, Jernigan TL, for the CHARTER Group
Date: 11-13-2010
Abstract:Background: Human immunodeficiency virus (HIV) is a retrovirus that targets the immune system and enters the central nervous system (CNS) early in the course of infection and frequently results in neurologic dysfunction. Despite significant advances in anti-retroviral therapy (ART), CNS effects of HIV have remained prevalent. Neuroimaging may provide sensitive biomarkers to guide treatment, monitor therapeutic intervention, and identify individuals at risk for CNS decline. The national, multi-site CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) initiative has acquired magnetic resonance imaging (MRI) data to assess the brain’s response to HIV infection and treatment. Our recent study of 206 HIV+ individuals demonstrated associations between the level of most severe prior immunosuppression (nadir CD4), brain volume loss, and white matter damage. Of particular interest, findings also suggested an unexpected relationship between higher current CD4 levels, lower white and subcortical gray volumes, and increased cerebrospinal fluid (CSF). Methods: In this follow-up study, we examined longitudinal changes in a subset of this cohort with two MRI visits (n=63). Structural morphometry with multi-channel (T1, T2, and PD) segmentation and anatomical labeling indentified and measured isolated regions of abnormality in the white matter (e.g., hyperintensities on T2) along with total white matter, subregions of gray matter, and CSF volumes. A simultaneous multiple linear regression model was used to predict change in each MRI measure. Control variables in the model included age, scanner, time between scans, cranial vault volume, and serologic evidence of hepatitis C infection, a common comorbidity. Our primary variables of interest in the model were nadir CD4, detection of HIV RNA in CSF at baseline, and change in current CD4 level between visits. All morphometric variables and CD4 counts were log or square root transformed. Results: Current CD4 levels increased by >50 points in 33% of the sample. Results demonstrate that, in this subsample, increasing (improving) CD4 counts over time were related to increasing abnormal white matter (t=2.4, p<.05) and subcortical gray (t=2.6, p<.05), and reduced ventricular (t=-2.4, p<.05) volume. Detectable CSF viral load at baseline also tended to predict increasing abnormal white and gray matter volumes, although these effects did not reach significance (p<.15). Conclusions: These preliminary longitudinal findings suggest that brain tissue alterations in HIV-infection reflect both the cumulative history of HIV-related effects and potentially dynamic episodes of injury and repair over time that may be related to inflammation and immune recovery.