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Abstract #0024

Reduction of Brain Virus by Minocycline and Combination Anti-Retroviral Therapy Produces Neuronal Protection in a Primate Model of AIDS

Eva-Maria Ratai1, 2, Robert J. Fell3, Julian He, 23, Michael Piatak4, Jeffrey D. Lifson5, Tricia H. Burdo6, Jennifer Campbell6, Patrick Autissier6, Lakshmanan Annamalai7, Eliezer Masliah8, Susan V. Westmoreland, 27, Kenneth C. Williams6, R Gilberto Gonzlez, 23

1Neuroradiology Division, Department of Radiology , A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital , Charlestown, MA, United States; 2Harvard Medical School; 3Neuroradiology Division, Department of Radiology, A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States; 4SAIC Frederick, Inc., Frederick, MD, United States; 5SAIC Frederick, Inc., Frederick, MD, United States; 6Biology Department, Boston College, Chestnut Hill, MA, United States; 7Department of Pathology, New England Primate Research Center, Southborough, MA, United States; 8Department of Neurosciences, University of California at San Diego, La Jolla, CA, United States

MR spectroscopy was used to investigate the neuropathogenesis of HIV-Associated Neurocognitive Disorders (HAND). Twenty-three simian immunodeficiency virus-infected, CD8- T-lymphocyte depleted rhesus macaques were studied. Antiretroviral therapy and minocycline were used to modulate their disease progression. Both treatments resulted in the decrease of viral RNA in the brain. Severity of neuronal damage measured by NAA/Cr was shown to be dependent on CNS viral levels. The degree of CNS viral infection was directly influenced by plasma viral load and infected/activated monocytes that traffic virus into the brain. These findings suggest monocyte-directed therapies for a future direction of HAND treatment.

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Keywords

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