title: The protease inhibitor combination lopinavir/ritonavir does not decrease insulin secretion in healthy, HIV-seronegative volunteers.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, University of California, CA, USA.
authors.forename: Vivian Y
authors.initials: VY
authors.lastname: Pao
authors.forename: Grace A
authors.initials: GA
authors.lastname: Lee
authors.forename: Steven
authors.initials: S
authors.lastname: Taylor
authors.forename: Francesca T
authors.initials: FT
authors.lastname: Aweeka
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Schwarz
authors.forename: Kathleen
authors.initials: K
authors.lastname: Mulligan
authors.forename: Morris
authors.initials: M
authors.lastname: Schambelan
authors.forename: Carl
authors.initials: C
authors.lastname: Grunfeld
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D004338:Drug Combinations; D015309:Glucose Clamp Technique; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D018023:HIV Seronegativity; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050356:Lipid Metabolism / Q000187:drug effects; D008074:Lipoproteins / Q000378:metabolism; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D011744:Pyrimidinones / Q000008:administration & dosage / Q000494:pharmacology*; D019438:Ritonavir / Q000008:administration & dosage / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D007328:Insulin; D008074:Lipoproteins; D011744:Pyrimidinones; D014280:Triglycerides; C030104:lipoprotein cholesterol; D061466:Lopinavir; D002784:Cholesterol; D019438:Ritonavir