The effects of HIV protease inhibitors atazanavir and lopinavir/ritonavir on insulin sensitivity in HIV-seronegative healthy adults.

Abstract

BACKGROUND:

Therapy with some HIV protease inhibitors (PI) contributes to insulin resistance and type 2 diabetes mellitus, by inhibition of insulin-sensitive glucose transporters. Atazanavir (ATV) is a new PI with substantially less in vitro effect on glucose transport than observed with other PI, including lopinavir (LPV) or ritonavir (RTV).

METHODS:

Randomized, double-blind, crossover study of the effect of 5 days of administering ATV, lopinavir/ritonavir (LPV/r) or placebo on insulin-stimulated glucose disposal in 30 healthy HIV-negative subjects. Each subject was studied on two of three possible treatments with a wash-out period between treatments.

RESULTS:

The mean insulin-stimulated glucose disposal (mg/min per kg body weight) per unit insulin (microU/ml) (M/I) was 9.88, 9.80 and 7.52 for placebo, ATV and LPV/r, respectively (SEM, 0.84 for all). There was no significant difference between ATV and placebo. The M/I for LPV/r was 23% lower than that for ATV (P = 0.010) and 24% lower than that for placebo (P = 0.008). The mean glycogen storage rates were 3.85, 4.00 and 2.54 mg/min per kg for placebo, ATV and LPV/r, respectively (SEM, 0.39 for all). There was no significant difference between ATV and placebo. The glycogen storage rate for LPV/r was 36% lower than ATV (P = 0.003) and 34% lower than placebo (P = 0.006).

CONCLUSIONS:

ATV given to healthy subjects for 5 days did not affect insulin sensitivity, while LPV/r induced insulin resistance. This observation is consistent with differential in vitro effects of these PI on glucose transport. Further data are needed to assess clinical implications for body composition.

• Authors: Mustafa A Noor, Rex A Parker, Edward O'Mara, Dennis M Grasela, Alexander Currie, Sally L Hodder, Fred T Fiedorek, David W Haas
• Journal: AIDS (London, England) (AIDS) Vol. 18 Issue 16 Pg. 2137-44 (Nov 05 2004) ISSN: 0269-9370 [Print] England
• PMID: 15577646 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Fatty Acids, Nonesterified
• HIV Protease Inhibitors
• Lipids
• Oligopeptides
• Pyridines
• Pyrimidinones
• Lopinavir
• Atazanavir Sulfate
• Glycogen

Topics

• Adult
• Analysis of Variance
• Atazanavir Sulfate
• Cross-Over Studies
• Double-Blind Method
• Energy Metabolism
• Fatty Acids, Nonesterified (blood)
• Glycogen (metabolism)
• HIV Protease Inhibitors (pharmacology)
• HIV Seronegativity
• Humans
• Insulin Resistance
• Lipids (blood)
• Lipodystrophy (metabolism)
• Lopinavir
• Oligopeptides (pharmacology)
• Pyridines (pharmacology)
• Pyrimidinones (pharmacology)