Boosting dose ritonavir does not alter peripheral insulin sensitivity in healthy HIV-seronegative volunteers.
BACKGROUND
Some HIV protease inhibitors (PIs), including full-dose ritonavir (800 mg) and ritonavir-boosted lopinavir, acutely induce insulin resistance in the absence of HIV infection and changes in body composition. Boosting dose ritonavir (100-200 mg) is the most commonly prescribed PI, yet its effects on glucose metabolism have not been described in the absence of another PI.


METHODS
In this randomized, double-blind, cross-over study, a single dose of ritonavir 200 mg or placebo was given to healthy HIV-seronegative volunteers before assessment of insulin sensitivity by euglycemic hyperinsulinemic clamp.


RESULTS
Boosting dose ritonavir had no effect on insulin-mediated glucose disposal (M/I, placebo: 8.59 ± 0.83 vs. ritonavir: 8.51 ± 0.64 mg/kg per minute per μU/mL insulin, P = 0.89).


CONCLUSIONS
A single boosting dose of ritonavir does not alter insulin sensitivity, suggesting lopinavir is likely responsible for the induction of insulin resistance demonstrated in prior short-term studies of lopinavir/ritonavir. There is a dose-dependent effect of ritonavir on insulin sensitivity.
Taylor
Steven A
SA
Department of Medicine, University of California, San Francisco, CA, USA.
Lee
Grace A
GA
Pao
Vivian Y
VY
Anthonypillai
Jayaranjan
J
Aweeka
Francesca T
FT
Schwarz
Jean-Marc
JM
Mulligan
Kathleen
K
Schambelan
Morris
M
Grunfeld
Carl
C
D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005947:Glucose / Q000378:metabolism; D006805:Human Experimentation; D006801:Humans; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects*
D019380:Anti-HIV Agents; D007328:Insulin; D010919:Placebos; D005947:Glucose; D019438:Ritonavir