Statin Use in HIV Patients Taking Protease Inhibitors

HIV infection is a proinflammatory condition predisposing patients to arteriosclerosis, diabetes mellitus, dyslipidemia, and vascular thrombosis.

HIV-positive patients have up to twice the risk of cardiovascular disease than the general population independent of hypertension, cholesterol, and smoking. The Veterans Aging Cohort Study found that HIV-infected patients are 50% more likely to experience acute myocardial infarction, as well.

HIV patients receiving antiviral therapy with protease inhibitors are particularly at risk, as protease inhibitors increase serum cholesterol and triglyceride levels, induce insulin resistance and coronary artery calcification, and cause central obesity. Statins, which act on intracellular adhesion molecule-1, have effects beyond dyslipidemia, including reducing viral particle production and preventing viral cellular entry.

Providers prefer pravastatin in HIV patients because it has fewer drug-drug interaction potential with protease inhibitors. However, past studies enrolling HIV-positive patients have found that statins’ serum lipid effects are inconsistent.

The journal Pharmacological Research published an article ahead-of-print indicating that the statin class reduces HIV-infected patients’ low-density lipoprotein (LDL) and total cholesterol, while it raises high-density lipoprotein (HDL) cholesterol and has no effect on triglycerides. This meta-analysis surveyed randomized, controlled trials published as of October 2015 with either parallel or cross-over designs using statins for lipid control.

Statins decreased mean LDL, total, and non-HDL cholesterol by 27.8 mg/dL, 39.8 mg/dL, and 31.3 mg/dL, respectively. Statins increased HDL cholesterol by 2.8 mg/dL and decreased triglycerides by a statistically insignificant 14.3 mg/dL.

All studies found that statins affected LDL and HDL cholesterol similarly, and atorvastatin was slightly more effective for lowering total cholesterol. A 2015 study found that fluvastatin and pravastatin were the safest to use with protease inhibitors, suggesting that providers dose-reduce atorvastatin and closely monitor for toxicity, as well as avoid lovastatin and simvastatin in HIV positive patients.

Protease inhibitors decrease the area under the curve of pravastatin. Researchers hypothesize that this effect is caused by competition at the p-glycoprotein pump. A large double-blind placebo-controlled trial is underway using pitavastatin for cardiovascular disease primary prevention.

This meta-analysis confirmed that statins lower HIV infected patients’ LDL, total, and non-HDL cholesterol, boost HDL cholesterol, and don’t affect triglycerides. Large-scale, randomized, controlled trials are needed to compare the relative intraclass efficacy of statins.