2nd International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 13-15 September 2000, Toronto, Canada

USE OF HIV PROTEASE INHIBITORS IS ASSOCIATED WITH ENDOTHELIAL DYSFUNCTION

Antiviral Therapy 2000; 5(Suppl. 5):16 (abstract no. O24)

J Sosman, M Klein, J Bellehumeur, S Aeschlimann and J Stein
University of Wisconsin, Madison, Wis., USA

OBJECTIVES: Although the use of HIV protease inhibitors (HIV PIs) is associated with central obesity, hypertriglyceridemia and glucose intolerance, it is not clear if these metabolic changes are atherogenic. To determine if use of HIV PIs impairs endothelial function, flow-mediated vasodilation (FMD) of the brachial artery (BA) was measured in 37 subjects with HIV infection.

DESIGN: A cross-sectional analysis was performed on non-smoking adults with HIV-1 infection who had been on a stable antiretroviral regimen for ≥6 months. Twenty-two subjects were receiving HIV PIs (PI); 15 were not (non-PI). FMD was measured by high-resolution BA ultrasound. Images were stored digitally and analysed in triplicate by two blinded readers.

RESULTS: PI and non-PI subjects were similar in regard to age (42±7 years), gender (78% men), time since diagnosis of HIV infection (88±38 months) and CD4 cell count (409±254/ml), all P≥0.290. PI subjects had impaired FMD, indicative of significant endothelial dysfunction (2.6±4.6%), but FMD was normal in non-PI subjects (8.1±6.7%, P=0.005). PI subjects weighed more (26.9 versus 23.7 kg/m², P=0.069) and had higher triglycerides (298 versus 170 mg/dl, P=0.023), but total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting glucose, and systolic blood pressure (SBP) levels were similar in both groups. In forward step-wise regression analysis, use of HIV PIs, SBP,heart rate, and BA diameter independently predicted FMD (all P<0.001). A multiple linear regression model that incorporated these variables explained 67.1% (r²) of the variance in FMD.

CONCLUSIONS: Use of HIV protease inhibitors is associated with endothelial dysfunction. The metabolic changes observed with these medications may predispose to atherosclerosis and increased vascular risk. As survival of HIV-infected individuals increases, atherosclerotic vascular disease may become an important HIV-related complication.

000913
O24

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