Multiple mechanisms appear to contribute to neuronal stress and injury underlying HIV-associated neurocognitive disorders (HAND), which occur despite the successful introduction of combination antiretroviral therapy (cART). Evidence is accumulating that components of cART can itself be neurotoxic upon long-term exposure. In addition, abuse of psychostimulants, such as methamphetamine (METH), seems to compromise antiretroviral therapy and aggravate HAND. However, the combined effect of virus and recreational and therapeutic drugs on the brain is still incompletely understood. However, several lines of evidence suggest a shared critical role of oxidative stress, compromised neuronal energy homeostasis and autophagy in promotion and prevention of neuronal dysfunction associated with HIV-1 infection, cART and psychostimulant use. In this review, we present a synopsis of recent work related to neuronal stress and injury induced by HIV infection, antiretrovirals (ARVs) and the highly addictive psychostimulant METH.
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