Pitavastatin is approved in the U.S. but not yet in Canada for the normalization of cholesterol levels. A clinical trial of pitavastatin, called Reprieve, is underway in Canada and other countries.

Pitavastatin is a potent statin. A one-year clinical trial has found that it can help to normalize cholesterol levels in HIV-positive people. This study was called Intrepid and compared the effects of 4 mg/day of pitavastatin against an older statin called pravastatin (40 mg/day) in 252 HIV-positive participants. Researchers found that levels of “bad” cholesterol (LDL-C) were reduced by about 31% in pitavastatin users vs. 21% in pravastatin users. Pitavastatin was able to significantly reduce the following measures of inflammation:

• levels of oxidized LDL-C (which can increase inflammation in the arteries)
• a protein called soluble CD14 (some studies have found elevated levels of sCD14 to be associated with HIV-related inflammation and immune activation)
• an enzyme called Lp-PLA2 (which is associated with inflammation in HIV-negative people; HIV-positive people can have elevated levels of this enzyme, which is associated with an increased risk for cardiovascular disease in both HIV-negative and HIV-positive people)

Taken together, these reductions in proteins associated with inflammation and the decrease of bad cholesterol strongly suggest that long-term use of pitavastatin has potential to reduce the risk of heart attack and stroke.

Importantly, neither drug increased the risk for developing type 2 diabetes.

In general, both drugs were well tolerated. Common side effects in the study were as follows:

• diarrhea (in 10% of pitavastatin users)
• upper respiratory tract infection (in 10% of pravastatin users)

The results from Intrepid strongly support the ongoing Reprieve clinical trial to assess pitavastatin’s impact on reducing the risk of heart attack, stroke and death from cardiovascular complications. More information about the Reprieve study appears later in this issue of TreatmentUpdate.

—Sean R. Hosein

REFERENCES:

1. Aberg JA, Sponseller CA, Ward DJ, et al. Pitavastatin versus pravastatin in adults with HIV-1 infection and dyslipidaemia (INTREPID): 12-week and 52-week results of a phase 4, multicentre, randomised, double-blind, superiority trial. Lancet HIV. 2017 Jul;4(7):e284-e294.
2. Toribio M, Fitch KV, Sanchez L, et al. Effects of pitavastatin and pravastatin on markers of immune activation and arterial inflammation in HIV. AIDS. 2017 Mar 27;31(6):797-806.