THE ROLE OF OXIDATIVE STRESS IN HIV DISEASE

Evidence has accumulated suggesting that HIV-infected patients are und er chronic oxidative stress. Perturbations to the antioxidant defense system, including changes in levels of ascorbic acid, tocopherols, car otenoids, selenium, superoxide dismutase, and glutathione, have been o bserved in various tissues of these patients. Elevated serum levels of hydroperoxides and malondialdehyde also have been noted and are indic ative of oxidative stress during HIV infection. Indications of oxidati ve stress are observed in asymptomatic HIV-infected patients early in the course of the disease. Oxidative stress may contribute to several aspects of HIV disease pathogenesis, including viral replication, infl ammatory response, decreased immune cell proliferation, loss of immune function, apoptosis, chronic weight loss, and increased sensitivity t o drug toxicities. Glutathione may play a role in these processes, and thus, agents that replete glutathione may offer a promising treatment for HIV-infected patients. Clinical studies are underway to evaluate the efficacy of the glutathione-repleting agents, L-2-oxothiazolidine- 4-carboxylic acid (OTC) and N-acetylcysteine (NAG), in HIV-infected pa tients.