Oxidative stress and therapeutic approaches in HIV dementia

Despite the rapidly increasing incidence of HIV infection worldwide and the increasing prevalence of HIV-associated cognitive impairment, even in patients adequately treated with antiretroviral therapy, currently no effective treatment exists for HIV dementia. A broad range of studies using either brain or cerebrospinal fluid (CSF) tissues from well-characterized patients with HIV dementia, animal models, and in vitro studies from several laboratories using HIV-infected cells or HIV proteins provide overwhelming evidence for oxidative stress in mediating neuronal injury in this patient population. These studies also suggest that patients with apolipoprotein E (ApoE) 4 allele are more susceptible to such oxidative damage. In this review, we provide a critical analysis of these studies, including the few clinical trials that have used antioxidants to treat HIV dementia. We also discuss several novel agents with potent antioxidative properties and provide a rationale for combination antioxidant and neuroprotective therapy.