The metabolic effects of lopinavir/ritonavir in HIV-negative men.
BACKGROUND
Therapy with HIV protease inhibitors (PI) has been shown to worsen glucose and lipid metabolism, but whether these changes are caused by direct drug effects, changes in disease status, or body composition is unclear. Therefore, we tested the effects of the PI combination lopinavir and ritonavir on glucose and lipid metabolism in HIV-negative subjects.


METHODS
A dose of 400 mg lopinavir/100 mg ritonavir was given twice a day to 10 HIV-negative men. Fasting glucose and insulin, lipid and lipoprotein profiles, oral glucose tolerance, insulin sensitivity by euglycemic hyperinsulinemic clamp, and body composition were determined before and after lopinavir/ritonavir treatment for 4 weeks.


RESULTS
On lopinavir/ritonavir, there was an increase in fasting triglyceride (0.89 +/- 0.15 versus 1.63 +/- 0.36 mmol/l; P = 0.007), free fatty acid (FFA; 0.33 +/- 0.04 versus 0.43 +/- 0.06 mmol/l; P = 0.001), and VLDL cholesterol (15.1 +/- 2.6 versus 20 +/- 3.3 mg/dl; P = 0.05) levels. There were no changes in fasting LDL, HDL, IDL, lipoprotein (a), or total cholesterol levels. Fasting glucose, insulin, and insulin-mediated glucose disposal were unchanged, but on a 2 h oral glucose tolerance test glucose and insulin increased. There were no changes in weight, body fat, or abdominal adipose tissue by computed tomography.


CONCLUSIONS
Treatment with 4 weeks of lopinavir/ritonavir in HIV-negative men causes an increase in triglyceride levels, VLDL cholesterol, and FFA levels. Lopinavir/ritonavir leads to a deterioration in glucose tolerance at 2 h, but there is no significant change in insulin-mediated glucose disposal rate by euglycemic hyperinsulinemic clamp.
Lee
Grace A
GA
Metabolism Section (111F), San Francisco Department of Veterans Affairs Medical Center, San Francisco, CA 94121, USA. galee@itsa.ucsf.edu
Seneviratne
Tara
T
Noor
Mustafa A
MA
Lo
Joan C
JC
Schwarz
Jean-Marc
JM
Aweeka
Francesca T
FT
Mulligan
Kathleen
K
Schambelan
Morris
M
Grunfeld
Carl
C
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001823:Body Composition / Q000187:drug effects; D015243:Cholesterol, VLDL / Q000097:blood; D004338:Drug Combinations; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015309:Glucose Clamp Technique / Q000379:methods; D005951:Glucose Tolerance Test / Q000379:methods; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D018023:HIV Seronegativity / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood*; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D011744:Pyrimidinones / Q000494:pharmacology*; D019438:Ritonavir / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D015243:Cholesterol, VLDL; D004338:Drug Combinations; D005230:Fatty Acids, Nonesterified; D017320:HIV Protease Inhibitors; D007328:Insulin; D008055:Lipids; D011744:Pyrimidinones; D014280:Triglycerides; D061466:Lopinavir; D019438:Ritonavir