HIV Treatment Bulletin - Vol. 6, No. 1, December 2004 / January 2005
Graham McKerrow, HIV i-Base

Treatment for 4 weeks with indinavir (IDV, Crixivan) monotherapy markedly impairs endothelial function and insulin-mediated vasodilation, without significant impairment of whole-body glucose disposal, according to an American study. So it appears unlikely that insulin resistance plays a major role in the induction of endothelial dysfunction.

Dubé and colleagues hypothesised that IDV-induced endothelial dysfunction occurred because of IDV-induced insulin resistance. Their study assessed insulin sensitivity, endothelial function, and insulin-mediated vasodilation in 16 lean, healthy, male subjects before and after 4 weeks of IDV 800mg TID.

Subjects were 37±3 years old, with BMI of 25±1 kg/m², body fat of 19.6±1.9%, total cholesterol: 171±8 mg/dL; LDL-cholesterol: 98±7 mg/dL; HDL-cholesterol: 50±4 mg/dL; triglycerides: 140±39 mg/dL, and resting leg blood flow (LBF) of 0.207±0.015 L/min. There was no significant change in any of these parameters after IDV. Plasma adiponectin levels increased after IDV (16.4±2.2 µg/ml pre-IDV, 19.1±2.3 µg/ml post-IDV, p<0.05). Normal, robust endothelium-dependent and insulin-mediated vasodilatory responses were present at baseline. After IDV, there was a marked blunting of endothelium-dependent vasodilation (258±43% pre-IDV vs 60±13% post, p<0.05) and insulin-mediated vasodilation (70±10% pre-IDV vs 16±6% post, p<0.05). In spite of these dramatic effects on vascular function, there was no significant change in the steady-state whole body glucose-disposal rate with IDV (8.0±0.6 mg/kg/min pre-IDV vs 7.5±0.6 post, p=NS).

Ref: Dubé MP, Shankar SS, Considine RV et al. Marked impairment of endothelial function without insulin resistance in healthy men treated with the HIV-1 protease inhibitor indinavir. Antiviral Therapy 2004; 9:L55 Abstract 95.

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