Effect of ritonavir on lipids and post-heparin lipase activities in normalsubjects

Background: Intensive therapy of HIV infection with highly active antiretro viral therapy (HAART) dramatically reduces viral loads and improves immune status. Abnormalities of lipid levels, body fiat distribution, and insulin resistance have been commonly reported after starting HAART. Whether the li pid abnormalities result from changes in metabolism after an improvement in HIV status or are partly attributable to the effects of protease inhibitor use is unknown. Methods: Twenty-one healthy volunteers participated in a 2 week double-blin d, placebo-controlled study on the effect of the protease inhibitor ritonav ir on total lipids, apolipoproteins, and post-heparin plasma lipase activit ies. Results: Those taking ritonavir (n = 11) had significantly higher levels of plasma triglyceride, VLDL cholesterol, IDL cholesterol, apolipoprotein B, and lipoprotein (a) compared with placebo (n = 8). HDL cholesterol was lowe r with therapy as a result of a reduction in HDL3 cholesterol. Post-heparin lipoprotein lipase (LpL) activity did not change but hepatic lipase activi ty decreased 20% (P < 0.01) in those taking ritonavirr-compared with placeb o. Although all lipoprotein subfractions became triglyceride enriched, most of the increase in triglyceride was in VLDL and not in IDL particles. Conclusion: Treatment with ritonavir in the absence of HIV infection or cha nges in body composition results in hypertriglyceridem ia that is apparentl y not mediated by impaired LpL activity or the defective removal of remnant lipoproteins, but could be caused by enhanced formation of VLDL. Long-term studies of patients with HIV infection receiving HAART will be necessary t o determine the impact of these drugs and associated dyslipidemia on the ri sk of coronary artery disease. (C) 2000 Lippincott Williams & Wilkins.