Neurotoxic profiles of HIV, psychostimulant drugs of abuse, and their concerted effect on the brain: Current status of dopamine system vulnerability in NeuroAIDS

There are roughly 30-40 million HIV-infected individuals in the world as of December 2007, and drug abuse directly contributes to one-third of all HIV infections in the United States. Antiretroviral therapy has increased the lifespan of HIV-seropositives, but CNS function often remains diminished, effectively decreasing quality of life. A modest proportion may develop HIV-associated dementia, the severity and progression of which is increased with drug abuse. HIV and drugs of abuse in the CNS target subcortical brain structures and DA systems in particular. This toxicity is mediated by a number of neurotoxic mechanisms, including but not limited to, aberrant immune response and oxidative stress. Therefore, novel therapeutic strategies must be developed that can address a wide variety of disparate neurotoxic mechanisms and apoptotic cascades. This paper reviews the research pertaining to the where, what, and how of HIV and cocaine/methamphetamine toxicity in the CNS. Specifically, where these toxins most affect the brain, what aspects of the virus are neurotoxic, and how these toxins mediate neurotoxicity. (C) 2008 Elsevier Ltd. All rights reserved.