This chapter reviews the epidemiology, clinical manifestations, and pathology of HIV-1-associated neurological disease and its associated encephalitis. Particular emphasis is placed on diagnosis, pathogenesis, and treatment options now available or under investigation. This chapter demonstrates how HIV-1 infection of the brain results in neuronal injury and death. Besides the significant morbidity induced by HIV-1 for cognitive, motor, and behavioral function, the CNS represents an important reservoir for continuous virus production and the emergence of viral strain variance. Moreover, the mechanisms of how mononuclear phagocytes (MP) secretory products may damage neurons have potential wide applicability for other neurodegenerative disorders where inflammation is an important component of disease pathogenesis. Adjunctive therapies such as N-methyl D-aspartate receptor (NMDAR) blockers, chemokine and cytokine effectors, antioxidants, caspase inhibitors, and p38MAPK inhibitors are all potential interventions and are being developed by many laboratories. If successful, these drugs may find utility in a broad range of neurodestructive processes.
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