Oxidative Stress, Micronutrients, and HIV Dementia

Cognitive impairment associated with human immunodeficiency virus (HIV) infection continues to be quite prominent, despite the widespread use and effectiveness of combined antiretroviral drug therapy (cART). Thus, while mortality associated with HIV infection has been significantly reduced by cART, these regimens show only modest central nervous system penetrability, and many HIV-infected individuals show evidence of neurocognitive decline that may produce a progressive dementia. An imbalance of endogenous antioxidant defenses and generation of reactive oxygen species (ROS) is a common characteristic of HIV infection, and preclinical evidence implicates some HIV virotoxins in stimulating the production of ROS to promote neurodegeneration. Antioxidant approaches to address ROS activity produced by these virotoxins have been employed in preclinical models and demonstrate effectiveness in attenuating neurodegeneration produced by exposure to the virotoxins Tat and gp120. However, only a modest clinical literature exists with regard to effects of vitamin E and other antioxidant compounds on HIV progression and HIV-associated cognitive impairment. Findings of these studies demonstrate either no or modest effects of antioxidant regimens on HIV-associated cognitive impairment. Thus, the current state of opinion on the possible efficacy of antioxidant approaches to treat HIV-associated neurocognitive impairment remains unresolved, as a clear need for additional research is evident.