HIV Therapies and Atherosclerosis

The widespread use of nucleoside analog reverse transcriptase inhibitors (NRTIs) and HIV protease inhibitors (PIs) in Western countries has substantially reduced morbidity and mortality in patients with HIV infection. Concomitantly, however, adverse effects associated with long-term use of these agents are becoming recognized. A growing body of literature suggests that many adverse effects associated with the use of NRTIs such as lactic acidosis, hepatic steatosis, myopathy, cardiomyopathy, peripheral neuropathy, pancreatitis and lipodystrophy syndrome are due to mitochondrial toxicity.1–4 In contrast, the adverse effects associated with the use of PIs, hyperlipidemia, lipodystrophy,5 and perhaps, the resulting accelerated atherosclerosis,6,7 have not been attributed to mitochondrial toxicity. In the October 2002 issue of Atherosclerosis, Thrombosis and Vascular Biology, Zhong et al8 challenge this paradigm by demonstrating PI-mediated mitochondrial dysfunction in endothelial cells and the resultant apoptosis-independent cytotoxicity and suggest that PI-induced endothelial cell toxicity contributes to accelerated atherosclerosis in HIV patients.