Effects of statins on endothelial function and lipid profile in HIV infected persons receiving protease inhibitor-containing anti-retroviral combination therapy: a randomised double blind crossover trial.

I ntroduction of anti-retroviral combination therapy has profoundly altered both the course and prognosis of the disease in HIV infected persons. Recent data, however, have raised concerns that anti-retroviral combination therapy is associated with premature manifestation of coronary artery disease. In particular, protease inhibitors have been linked to metabolic changes such as insulin resistance, abnormalities in lipid metabolism and lipodystrophy, and increased coronary artery calcification. While previous studies have reached conflicting conclusions about the incidence of myocardial infarction, the most substantial database recently provided by Friis-Møller and co-workers demonstrated an increased incidence in HIV infected persons receiving protease inhibitors or non-nucleoside reverse transcriptase inhibitor-containing therapy. One of the postulated mechanisms of pro-atherogenic effects of protease inhibitors is the promotion of atherosclerotic lesion formation by an increase in CD36-dependent cholesteryl ester accumulation in macrophages. Additionally, hypercholesterolaemia promotes a CD36-dependent and endothelial nitric oxide synthase mediated endothelial dysfunction. Endothelial dysfunction is associated with future risk of adverse cardiovascular events. Impaired endothelial function was previously shown in HIV infected persons receiving protease inhibitor therapy. The effect of statins (hydroxy-methyl-glutaryl coenzyme A reductase inhibitors) in anti-retroviral combination therapy associated dyslipidaemia remains to be determined. As most statins are metabolised by the cytochrome P450 3A4 isoform, and thus interfere with the metabolism of many anti-retroviral drugs, resulting in increased toxicity, cytochrome P450 independent statins, such as pravastatin, may be advantageous. Hence, the present study aimed to evaluate the effects of pravastatin on endothelial function and plasma lipid profile in persons on protease inhibitor-containing anti-retroviral combination therapy.