No Effect of Atazanavir or Lopinavir/r on Endothelial Function or Insulin Sensitivity

Keith Henry, MD


AIDS Clinical Care 

Unlike indinavir, atazanavir and lopinavir/ritonavir do not induce endothelial dysfunction or change insulin sensitivity in healthy, HIV-negative men.

PI use has been linked to an increased risk for cardiovascular disease (AIDS Clin Care Apr 25 2007). Dyslipidemia is at least partially responsible, but other mechanisms are also being explored. In previous studies, indinavir has been shown to cause both endothelial dysfunction and a decrease in insulin sensitivity. Now, investigators have evaluated these same parameters for the newer PIs atazanavir and lopinavir/ritonavir. (One of the investigators has consulted for or received research support from the makers of both drugs.)

Thirty healthy, nonobese, HIV-negative men were randomized to receive atazanavir (400 mg daily), lopinavir/r (400/100 mg twice daily), or placebo for 4 weeks. At baseline and week 4, participants were assessed for endothelial function (using methacholine and sodium nitroprusside infusion vasodilation studies) and for insulin sensitivity (using euglycemic hyperinsulinemic clamp studies). Neither drug had a significant effect on these parameters, leading the authors to conclude that endothelial dysfunction is not a class-specific effect of PIs.

The important point here is that the metabolic and vascular effects of individual PIs appear to be quite diverse. We await updated reports from ongoing major cohort studies to see whether the newer PI-based regimens still contribute excessively to increased cardiovascular risk.

— Keith Henry, MD

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