Elevated lactic acid in the bloodstream (hyperlactatemia) occurs in up to 20% of patients on antiretroviral therapy for HIV infection [1-11]. Hyperlactatemia may range from transient and asymptomatic, to rarely, a severe and potentially fatal lactic acidosis. However, we currently have no method to determine who is susceptible to developing these side effects or to detect toxicity prior to the development of symptoms. The precise metabolic changes that lead to hyperlactatemia have not been determined. Increases in both production and clearance of lactate may balance each other and lead to alterations in lactate metabolism being overlooked. The metabolic changes underlying hyperlactatemia may be more profound than the blood lactate level indicates. Understanding changes in lactate metabolism on antiretroviral therapy could provide the key to developing methods for early detection and prevention of toxicity from antiretroviral medications. We propose to conduct a cross sectional study of lactate production and clearance rates in HIV infected patients with and without toxicity from antiretroviral medications. Established [13C]lactate tracer """"""""methodology will be used to determine lactate production, metabolic clearance, oxidation and lactate to glucose conversion rates. We believe gaining this basic understanding of lactate metabolism is a key step in learning how to prevent and treat hyperlactatemia and other serious side effects of antiretroviral medications that result from mitochondrial toxicity.
