The protease inhibitor combination lopinavir/ritonavir does not decrease insulin secretion in healthy,...

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.

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.

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.

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.