Department of Health and Human Services - 0 views
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MiamiOH OARS on 13 Sep 18HIV-associated neurological disorders (HAND) persist in up to 50% of HIV-patients even when HIV replication is suppressed by combination antiretroviral therapy (cART), which transformed HIV/AIDS from a fatal illness into a chronically managed long-term condition. HIV does not infect neurons, but infects microglia and macrophages in the brain, causing HAND associated neuropathology. HAND epitomizes a series of disorders include Asymptomatic Neurocognitive Impairment (ANI), Mild Neurocognitive Disorder (MND), and HIV-Associated Dementia (HAD). These neurocognitive deficits interfere with psychomotor speed and coordination, diminishing memory and executive functions, and reduce quality of life in long-standing aviremic HIV-positive patients. These clinical challenges mandate research for a better understanding of HIV neuropathology; however, currently there are no effective approaches for HIV-infected live human brain studies or realistic HIV-infected animal models for HIV neuropathology. Proposed projects MUST include the following components. Applications which lack these three components will be considered non-responsive to the FOA and will not be reviewed. The major thrust of the project MUST involve exploitation of induced microglia and cerebral organoids generated from patient derived iPSC lines to better understand the molecular and cellular mechanisms of HIV-Associated Neurocognitive Disorder (HAND). At least one aim or sub-aim MUST also involve either 1. opioid, cannabinoid, methamphetamine, nicotinic, dopaminergic, or other signaling pathways relevant to addictive substance use, or 2. exposure to addictive substances, or 3. analysis of samples from patients that have used addictive substances or have SUDs.