Risk-benefit of HMG-CoA reductase inhibitors in the treatment of HIV protease inhibitor-related hyperlipidaemia

HIV protease inhibitors decrease mortality and improve quality of life in patients with HIV infection. However, these drugs have been associated with serum lipid elevations, which may pose an increased risk of cardiovascular disease and pancreatitis. Treatment of protease inhibitor-related hyperlipidaemia (PIH) is complicated by drug interactions, which significantly increase concentrations of most 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins). Although pravastatin and atorvastatin effectively lower cholesterol and triglyceride concentrations in HIV-infected patients, a significant number of patients did not achieve their National Cholesterol Education Program low density lipoprotein concentration goals. Nonetheless, due to the increased risk of rhabdomyolysis with elevated statin concentrations, atorvastatin should be considered a second-line agent. The limited available PIH data supports the fact that pravastatin and atorvastatin are well-tolerated in HIV-infected individuals. More data are needed on the appropriate starting doses, maximum safe doses, role of combination statin-fibrate therapy, documentation of coronary heart disease benefit and incidence of myotoxicity and hepatotoxicity. Pravastatin has an acceptable risk-benefit ratio in PIH, while theoretical toxicity concerns exist with atorvastatin.