Use of human immunodeficiency virus-1 protease inhibitors is associated with atherogenic lipoprotein changes and endothelial dysfunction

Background-Human immunodeficiency virus protease inhibitors (HIV PIs) are a ssociated with hyperlipidemia, hyperglycemia, and obesity; however, it is n ot known whether they increase risk of atherosclerotic vascular disease. Th e purposes of this study were to characterize the lipoprotein abnormalities associated with use of HIV PIs in individuals with HSV infection and to de termine the pathophysiological significance of these changes by assessing t heir effect on endothelial dysfunction. Methods and Results-This was a cross-sectional study of 37 adults with HIV- 1 infection who were receiving antiretroviral therapy. Twenty-two were taki ng HIV PIs (group 1); 15 were not (group 2). Lipids and lipoproteins were m easured by enzymatic techniques and nuclear magnetic resonance spectroscopi c analysis. Flow-mediated vasodilation (FMD) of the brachial artery was mea sured by high-resolution ultrasound. Subjects in both groups were similar i n regard to age, time since diagnosis of HIV infection, and CD4 cell count. Group 1 subjects had higher total cholesterol (5.68 versus 4.42 mmol/L, P= 0.007) and triglyceride (4.43 versus 1.98 mmol/L, P=0.009) levels, characte rized by elevated levels of IDL and VLDL. Subjects in group 1 had impaired FMD (2.6 +/-4.6%), indicative of significant endothelial dysfunction, Group 2 subjects had normal FMD (8.1 +/- 6.7%, P = 0.005). In group 1, chylomicr on, VLDL, IDL, and HDL cholesterol levels predicted FMD. Conclusions-Use of HIV PIs is associated with atherogenic lipoprotein chang es and endothelial dysfunction. Because these metabolic and vascular change s predispose to atherosclerosis, monitoring and treatment of dyslipidemia i n patients taking these medications is warranted.