Mechanisms of Neuronal Injury by Drugs of Abuse in Patients with HIV Infection

HIV infection is now largely driven by drug abusing populations and both HIV and drugs of abuse independently cause injury to the brain. However, researchers face multiple challenges in the design of studies that could address the combined effects of drugs of abuse and HIV infection. Drug abusers often use multiple drugs and the pattern of use may be erratic ranging from binge usage to drug withdrawal. Using in vitro models and transgenic animals with Hiv proteins, we have found that HIV proteins such as Tat and gp120 can synergize with opiates, cocaine or methamphetamine to cause neurotoxicity. This involves the activation of oxidative stress pathways, chemokine release and toxicity to dopaminergic pathways. We are now determining the effects of these substances on neural progenitor cells and are also determining the mechanisms by which the oxidative stress pathways are induced.