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Effects of nadir CD4 count and duration of human immunodeficiency virus infection on brain volumes in the highly active antiretroviral therapy era |
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| Authors: | Ronald A Cohen Jaroslaw Harezlak Giovanni Schifitto George Hana Uraina Clark Assawin Gongvatana Robert Paul Michael Taylor Paul Thompson Jeffery Alger Mark Brown Jianhui Zhong Thomas Campbell Elyse Singer Eric Daar Deborah McMahon Yuen Tso Constantin T Yiannoutsos Bradford Navia |
| Institution: | 1. Department of Psychiatry and Human Behavior and the Brain Science Program, Brown University School of Medicine, Providence, Rhode Island, USA 3. Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA 4. Department of Neurology, Rochester School of Medicine, Rochester, New York, USA 5. Department of Psychology, University of Missouri, St. Louis, Missousi, USA 6. Department of Psychiatry, University of California-San Diego, La Jolla, California, USA 7. Departments of Neurology and Radiological Science, University of California, Los Angeles, Westwood, California, USA 8. Departments of Psychiatry and Internal Medicine, University of Colorado-Denver, Aurora, Colorado, USA 9. Department of Medicine, Harbor-UCLA Medical Center, Los Angeles, CA, USA 10. Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA 11. Department of Neurology, Stanford University School of Medicine, Palo Alto, California, USA 12. Department of Public Health and Community Medicine, Tufts University School of Medicine, 150 Harrison Ave, 02111, Boston, MA 13. Department of Neurology, Tufts University School of Medicine, Boston, Massachusetts, USA |
| Abstract: | Cerebral atrophy is a well-described, but poorly understood complication of human immunodeficiency virus (HIV) infection. Despite reduced prevalence of HIV-associated dementia in the highly active antiretroviral therapy (HAART) era, HIV continues to affect the brains of patients with chronic infection. In this study we examine patterns of brain volume loss in HIV-infected patients on HAART, and demographic and clinical factors contributing to brain volume loss. We hypothesized that nadir CD4+ lymphocyte count, duration of HIV infection, and age would be associated with reduced cortical volumes. Volumes of cortical and subcortical regions in 69 HIV-infected neuroasymptomatic (NA) individuals and 13 with at least mild acquired immunodeficiency syndrome (AIDS) dementia complex (ADC) were measured using voxel-based morphometry. Demographic and clinical factors (age, plasma HIV RNA level, current and nadir CD4 counts, duration of infection, central nervous system CNS] penetration of antiretroviral regimen) along with their interactions were entered into a regression model selection algorithm to determine the final models that best described regional brain volumes. Relative to NA, individuals with ADC exhibited decreased total gray matter and parietal cortex volumes and increased total ventricular volumes. Final regression models showed overall cerebral volume, including gray and white matter volume and volumes of the parietal, temporal, and frontal lobes and the hippocampus, were most strongly associated with disease history factors (nadir CD4 and duration of infection). In contrast, basal ganglia volumes were related most strongly to current disease factors, most notably plasma HIV RNA. These findings indicate that individuals with a history of chronic HIV infection with previous episodes of severely impaired immune function, as reflected by reduced nadir CD4+ lymphocyte count, may be at greatest risk for cerebral atrophy. The pattern of HIV-associated brain loss may be changing from a subcortical to a cortical disease among patients who are largely asymptomatic on HAART. |
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