DRUG ABUSE AND NEURO-AIDS^*

In certain populations around the world, the HIV pandemic is driven by drug abuse. Mounting evidence suggests that these patient populations may have accelerated and more severe neurocognitive dysfunction as compared to non-drug abusing HIV infected populations. Many drugs of abuse are CNS stimulants, hence it stands to reason that these drugs may synergize with neurotoxic substances released during the course of HIV infection. Clinical and laboratory evidence suggest that the dopaminergic systems are most vulnerable to such combined neurotoxicity although multiple regions of the brain may be involved. Identifying common mechanisms of neuronal injury is critical to developing therapeutic strategies for drug abusing HIV-infected populations. This chapter reviews 1) the current evidence for neurodegeneration in the setting of combined HIV infection and use of methamphetamine, cocaine, heroin or alcohol, 2) the proposed underlying mechanisms involved in this combined neurotoxicity, and 3) future directions for research. This manuscript also suggests therapeutic approaches based on our current understanding of the neuropathogenesis of dementia due to HIV infection and drugs of abuse.