This Program Project outlines a group of studies investigating one of the most cotton and devastating complications of AIDS, a neurological disorder characterize by cognitive, motor and behavioral abnormalities which we have termed the AIDS dementia complex (ADC). A Core Section and six individual Projects propose a coordinated and complementary group of studies dealing with the clinical character, epidemiology, natural history, viral pathogenesis and pathological neurobiology of the ADC. The Core will serve an overall administrative function as well as include centralized neurological and neuropsychological instrumentation, virology and immunology core facilities, and centralized data management and analysis. Projects 1-3 outline clinical studies aimed at more precise definition of the character of the ADC, its neurological and neuropsychological profile, natural history and epidemiology, as well as its immunological, virological and neuroradiological correlates. These 3 projects focus on complementary HIV-infected populations, ranging from individuals with symptomatic ADC to groups with high, moderate and low risk for developing the ADC. Project 4 uses positron emission tomography (PET) and fluorodeoxyglucose to define the metabolic anatomy of the ADC, metabolic descriptors of severity and progression of the disorder, and response to antiviral therapy. Project 5 investigates the viral pathogenesis of the ADC, including the character and localization of human immunodeficiency virus (HIV) brain infection, and attempts to define neurotropic variants of HIV responsible for the ADC using tissue culture systems and direct genetic sequence analysis. Project 6 evaluates the nature and localization of the T4 molecule, which serves as the cellular receptor for HIV, in brain and also seeks to develop a mouse model of AIDS and the ADC.
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