The protease inhibitor combination lopinavir/ritonavir does not decrease insulin secretion in healthy, hiv-seronegative volunteers

BACKGROUND: HIV protease inhibitors have been shown to worsen glucose and lipid metabolism. Recent studies have suggested that protease inhibitors can impair insulin secretion in HIV-infected patients. We studied the effects of the protease inhibitor combination lopinavir and ritonavir on insulin secretion, insulin sensitivity, and lipid metabolism in HIV-negative persons. METHODS: A combination dose of lopinavir 400 mg and ritonavir 100 mg was given twice daily to eight HIV-seronegative men for 4 weeks. Fasting glucose, insulin, lipid, and lipoprotein profiles; oral glucose tolerance; insulin secretion and insulin-mediated glucose disposal by hyperglycemic clamp; and body composition by dual energy X-ray absorptiometry were determined before and after lopinavir/ritonavir administration. RESULTS: There was no change in first-phase insulin secretion (2.82 ± 0.30 versus 2.71 ± 0.31 nmol/l; P = 0.60), as well as fasting insulin and glucose levels, oral glucose tolerance, or insulin-mediated glucose disposal after 4 weeks administration of lopinavir/ritonavir. However, there were significant increases in fasting triglycerides (1.02 ± 0.13 versus 2.20 ± 0.31 mmol/l; P = 0.001), total cholesterol (4.42 ± 0.30 versus 5.70 ± 0.60 mmol/l; P = 0.007), and apo B-100 levels (0.86 ± 0.07 versus 1.07 ± 0.11 g/l; P = 0.0009). High-density lipoprotein cholesterol decreased (0.99 ± 0.11 versus 0.82 ± 0.10 mmol/l; P = 0.005). There were no changes in body composition, weight, or body fat. CONCLUSION: Although administration of lopinavir/ritonavir to healthy, HIV-seronegative volunteers for 4 weeks resulted in increased triglyceride and decreased high-density lipoprotein cholesterol levels, there was no change in first-phase insulin secretion during the hyperglycemic clamp. The reported effects of protease inhibitor on insulin secretion in HIV-infected individuals may be due to changes in HIV-related factors and not a direct drug effect.