The Reprieve study comes to Canada
HIV infection is associated with an increased risk for cardiovascular disease. Part of the reason for this is that, according to some studies, there are very high rates of smoking among HIV-positive people. However, even after accounting for smoking, other studies have found that HIV-positive people tend to have a higher level of inflammation and immune systems that are chronically activated. Together, this inflammation and activation likely worsen the risk for injury to vital organs and systems, including the cardiovascular system. Initiating potent combination anti-HIV therapy (ART) early in the course of HIV disease and achieving and maintaining an undetectable viral load greatly reduces but does not eliminate HIV-associated immune activation and inflammation. Therefore, researchers are seeking other ways to reduce immune activation and inflammation as well as cardiovascular risk.
Small studies of lipid-lowering drugs called statins, such as atorvastatin (Lipitor) and rosuvastatin (Crestor), have shown that these drugs can significantly reduce levels of bad cholesterol (LDL-C). However, because these studies have been small and short in duration, they could not show any impact of statin therapy on heart attacks, stroke or death arising from complications of cardiovascular disease.
Enter Reprieve
Researchers in the U.S., Canada and Thailand are conducting a large study called Reprieve. Approximately 6,500 HIV-positive people will be recruited; half will receive a relatively new statin called pitavastatin 4 mg/day and the other half will receive placebo. Pitavastatin has been approved in the U.S. and Japan but not yet in Canada. Although it is not approved in Canada, pitavastatin can be used in clinical trials here. Reprieve is expected to last for up to six years.
Advantages of Reprieve
Reprieve is a large well-designed placebo-controlled study. As a result, researchers will be able to determine whether pitavastatin is able to reduce heart attacks, stroke, deaths related to cardiovascular disease and the need for cardiovascular surgery to improve the flow of blood. Researchers will also explore pitavastatin’s ability to reduce inflammation and narrowing of the arteries.
Researchers enrolling participants for Reprieve will be seeking people who are at low or moderate risk for heart disease. For more information about Reprieve, see these links from the Canadian HIV Trials Network:
About pitavastatin
In clinical trials with HIV-negative people, pitavastatin has been found to be effective at reducing levels of bad cholesterol. The drug was also found to be generally safe. Some statins have been associated with a small but increased risk for developing type 2 diabetes. Pitavastatin does not appear to carry such a risk.
A placebo-controlled study of pitavastatin has been done with 24 HIV-positive people in Thailand. All participants entered the study with abnormal lipid levels and had been taking ART based on a combination of atazanavir (Reyataz) and ritonavir and nucleoside analogues. They took pitavastatin 4 mg/day or placebo for 12 weeks and then stopped. After two subsequent weeks participants who were taking pitavastatin were given placebo and vice versa for 12 consecutive weeks and then stopped. In this study, pitavastatin significantly reduced levels of total cholesterol and LDL-C. These changes were detectable in as little as four weeks after starting the drug.
No side effects were reported in that study.
There were no significant changes to liver enzymes or any lab test results suggestive of toxicity. There were also no significant changes to levels of atazanavir in the blood of participants. Previous studies had found that there are no significant interactions between pitavastatin and darunavir (Prezista), ritonavir or efavirenz (Sustiva and in Atripla).
—Sean R. Hosein
REFERENCES:
- Wongprikorn A, Sukasem C, Puangpetch A, et al. Effects of pitavastatin on lipid profiles in HIV-infected patients with dyslipidemia and receiving atazanavir/ritonavir: A randomized, double-blind, crossover study. PLoS One. 2016 Jun 15;11(6):e0157531.
- Sponseller CA, Morgan RE, Kryzhanovski VA, et al. Comparison of the lipid-lowering effects of pitavastatin 4 mg versus pravastatin 40 mg in adults with primary hyperlipidemia or mixed (combined) dyslipidemia: a Phase IV, prospective, US, multicenter, randomized, double-blind, superiority trial. Clinical Therapeutics. 2014 Aug 1;36(8):1211-22.
- Nakagomi A, Shibui T, Kohashi K, et al. Differential effects of atorvastatin and pitavastatin on inflammation, insulin resistance, and the carotid intima-media thickness in patients with dyslipidemia. Journal of Atherosclerosis and Thrombosis. 2015;22(11):1158-71.
- Chamberlin KW, Baker WL. Benefit-risk assessment of pitavastatin for the treatment of hypercholesterolemia in older patients. Clinical Interventions in Aging. 2015 Apr 16;10:733-40.
- Mitka M. Exploring statins to decrease HIV-related heart disease risk. JAMA. 2015 Aug 18;314(7):657-9.