The first clinical trial to investigate whether treatment with a statin drug can reduce the increased cardiovascular disease risk in people infected with HIV has begun enrolling patients. Based at Massachusetts General Hospital (MGH), the six-year, $40 million REPRIEVE (Randomized Study to Prevent Vascular Events in HIV) trial will be conducted at around 100 sites in the U.S., Canada, Puerto Rico and Thailand with funding from the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the AIDS Clinical Trials Group (ACTG) and support from the National Institutes of Allergy and Infectious Diseases. As recently reported by the NIH, the study is the largest study ever conducted to focus on cardiovascular disease in HIV patients,
"This is the first major cardiovascular prevention trial for HIV-infected patients, a population with a major increase in risk of myocardial infarction and stroke, and may have implications for a number of diseases in which inflammatory mechanisms contribute to increased cardiovascular disease rates," says Steven Grinspoon, MD, director of the MGH Program in Nutritional Metabolism, professor of Medicine at Harvard Medical School and a principal investigator of REPRIEVE. "If successful, the study will change practice and save lives by targeting patients who often have no symptoms of cardiovascular disease but are at increased risk."
Studies by Grinspoon's team and other groups over the past decade have demonstrated that the risks of heart attack and stroke in HIV-infected individuals are from 50 to 100 percent greater than in uninfected people, regardless of the presence of traditional cardiovascular risk factors. Since statin drugs reduce inflammation and immune system activation - both of which are elevated in HIV infection - along with lowering lipid levels, the research team is investigating whether they can reduce the HIV-associated increase in cardiovascular risk.
The study is open to HIV-infected men and women ages 40 to 75 who are on antiretroviral therapy and who have no known cardiovascular disease and low traditional risk factors. Participants will be randomized to receive either pitavastatin - which is known to reduce low-density lipoprotein cholesterol in HIV patients without interacting with antiretroviral therapy drugs - for up to 72 months. A total of 6,500 participants will be enrolled, and along with evaluating whether pitavastatin reduces the incidence of cardiovascular events, more detailed assessment of 800 participants will examine the drug's effects on arterial plaques and on biomarkers of inflammation. Udo Hoffmann, MD, MPH, chief of the Division of Cardiovascular Imaging in the MGH Department of Radiology and a professor of Radiology at Harvard Medical School will direct the coronary imaging analysis as principal investigator of the study's Data Coordinating Center.
"The REPRIEVE trial has the potential to change the standard of care with regard to cardiovascular disease for individuals living with HIV," said Daniel Kuritzkes, MD, ACTG Network principal investigator and chief, Division of Infectious Diseases, Brigham and Women's Hospital. "The ACTG Network is thrilled to collaborate with Dr. Grinspoon and his team in conducting this landmark study."
Potential participants in the Boston area should contact:
Massachusetts General Hospital
Theresa Flynn, RN, MSN, ANP, BSN,
Brigham and Women's Hospital
Cheryl Keenan, RN
Additional information, including a list or a map of currently available study sites, is available at the REPRIEVE TRIAL website (http://reprievetrial.
In addition to Grinspoon and Hoffmann, trial leadership includes co-principal investigators Pamela Douglas, MD, professor of Medicine at Duke University, and Heather Ribaudo, PhD, senior biostatistician at the Harvard School of Public Health. Study drugs and additional funding are being provided by Kowa Pharmaceuticals.
Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $760 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine.