Glucose Kinetics in HIV Infected Patients on Antiretroviral Therapy During Rest and Exercise

Abstract

Background. Nucleoside Reverse Transcriptase Inhibitor (NRTI) therapy for treatment of HIV infection has been implicated in causing mitochondrial toxicity, which may reduce oxidative capacity and can lead to lactic acidosis. We hypothesized that NRTI patients with elevated lactate turnover, but without lactic acidosis, would have increased rates of glycolysis and a greater reliance on non-oxidative means of glucose disposal via gluconeogenesis (GNG) compared with HIV uninfected historical controls (CON), previously reported in Bergman et al. 1999. Methods. Glucose turnover was determined with [6, 6-2H]glucose and lactate incorporation into glucose by use of [3-13C]lactate during 90 min of rest and 1 hr of cycle ergometry at 45% of each subject’s peak oxygen consumption (VO2peak). Results. There were no significant differences between CON (n=9) and NRTI (n=7) groups for glucose appearance rate (Ra, 2.4±.2 mg/kg/min), Rd (same), GNG (.11±.03mg/kg/min) and %glucose Ra from GNG (4.7±1.1%). Furthermore, within each group all parameters during exercise were significantly elevated over rest (+41–65%) except %glucose Ra from GNG. Conclusions. NRTI patients without lactic acidosis have normal glucose flux rates, comparable to CON. Substrate oxidation does not appear to be limited, suggesting mitochondrial toxicity is minimal when lactate levels are normal. NIH R21 AI 058770, R01 042906