In new study data, pitavastatin (Livalo, Kowa Pharmaceuticals America, Inc.) significantly reduced key arterial inflammation and immune-activation markers in patients with human immunodeficiency virus (HIV) infection receiving chronic antiretroviral therapy (ART) compared with pravastatin, a commonly prescribed statin for HIV-infected patients with dyslipidemia.
The INTREPID (HIV PatieNts and TREatment With Pitavastatin Versus PravastatIn for Dyslipidemia) trial was a randomized, double-blind, double-dummy, active-controlled, parallel-group, superiority study conducted at 45 sites in the United States and Puerto Rico. The study included 252 HIV-infected men and women who had received ART for more than six months. Select inflammatory and immune-activation biomarkers were assessed at baseline, at week 12, and at week 52. The participants were randomly assigned to receive pitavastatin 4 mg once daily and a matching pravastatin placebo or pravastatin 40 mg once daily and a matching pitavastatin placebo. Baseline demographic characteristics, including gender, total cholesterol, log HIV RNA, and baseline levels of inflammatory markers, were not significantly different between the two treatment groups.
At week 52, participants treated with pitavastatin demonstrated significantly greater reductions in soluble cluster of differentiation 14 (–8.2% versus 0.6%; P = 0.007), in oxidized low-density lipoprotein (–26.6% versus –17.6%; P = 0.02), and in lipoprotein-associated phospholipase A2 (–25.0% versus –14.9%; P = 0.003) compared with participants treated with pravastatin. Changes in other markers were similar between the two groups at 52 weeks. Superior reductions in low-density lipoprotein cholesterol (LDL-C) levels were seen in the pitavastatin group compared with the pravastatin group (–31% versus –21%, respectively). Adverse event profiles and overall safety were similar for pitavastatin 4 mg and pravastatin 40 mg.
Pitavastatin is a 3-hydroxy-3-methylglutaryl-coenzyme (HMG-CoA) reductase inhibitor indicated for patients with primary hyperlipidemia or mixed dyslipidemia as an adjunctive therapy to diet to reduce elevated total cholesterol, LDL-C, apolipoprotein B, and triglycerides, and to increase high-density lipoprotein cholesterol. It is a synthetic lipid-lowering agent for oral administration.
Pitavastatin inhibits HMG-CoA reductase, a rate-determining enzyme involved in the biosynthesis of cholesterol, in a manner of competition with the substrate so that it inhibits cholesterol synthesis in the liver. As a result, the expression of LDL receptors is accelerated, which in turn increases the uptake of LDL from the blood to the liver, and plasma total cholesterol decreases. In addition, the sustained inhibition of cholesterol synthesis in the liver reduces levels of very-low-density lipoproteins.
The findings were presented at the American Society for Microbiology Microbe 2016 conference in Boston.