Indinavir impairs endothelial function in healthy HIV-negative men

Background Potent antiretroviral treatment has drastically reduced mortality in HIV-infected patients but may accelerate atherosclerotic disease, which could be partially mediated via endothelial dysfunction. Methods In 8 HIV-negative healthy males, leg blood flow responses to intraartery infusions of methacholine chloride (Mch), sodium nitroprusside, and N G -mono-methyl-l-arginine (l-NMMA) were measured before and after 4 weeks of daily oral indinavir. In the same subjects, we also assessed the effect of indinavir on lipids, insulin sensitivity, markers of inflammation, as well as oxidative stress. Results After 4 weeks of indinavir, the endothelium-dependent response to methacholine chloride was impaired (195% ± 38% vs 83% ± 13%, P N G -mono-methyl-l-arginine (nitric oxide–dependent tone) was nearly abrogated (−30% ± 4% vs −1% ± 11%, P P P Conclusions Four weeks of the HIV-1 protease inhibitor indinavir, in the absence of HIV-1 infection, causes vascular dysfunction most likely at the level of endothelial nitric oxide production. The vascular dysfunction may be mediated partially by the concomitant induction of insulin resistance but other mechanisms cannot be ruled out.