Udo Hoffmann1, Michael T Lu2, Devvora Olalere2, Elizabeth C Adami2, Michael T Osborne2, Alex Ivanov2, John Sukumar Aluru2, Saeyun Lee2, Nadja Arifovic2, Edgar Turner Overton3, Carl J Fichtenbaum4, Judith A Aberg5, Beverly Alston-Smith6, Karin L Klingman6, Myron Waclawiw7, Tricia H Burdo8, Kenneth C Williams9, Markella V Zanni10, Patrice Desvigne-Nickens7, Katharine Cooper-Arnold7, Kathleen V Fitch10, Heather Ribaudo11, Pamela S Douglas12, Steven K Grinspoon10. 1. Cardiac MR PET CT Program and Department of Radiology, Massachusetts General Hospital, Boston, MA. Electronic address: uhoffmann@mgh.harvard.edu. 2. Cardiac MR PET CT Program and Department of Radiology, Massachusetts General Hospital, Boston, MA. 3. Division of Infectious Diseases, University of Alabama at Birmingham School of Medicine, Birmingham, AL. 4. Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, OH. 5. Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY. 6. DAIDS, NIAID, NIH, Bethesda, MD. 7. National Institutes of Health/National Heart, Lung, and Blood Institute, Bethesda, MD. 8. Department of Neuroscience, Temple University School of Medicine, Philadelphia, PA. 9. Department of Biology, Boston College, Chestnut Hill, MA. 10. MGH Program in Nutritional Metabolism and Harvard Medical School, Boston, MA. 11. Center for Biostatistics in AIDS Research, Department of Biostatistics, Harvard TH Chan School of Public Health, Boston, MA. 12. Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.
Abstract
BACKGROUND:People with HIV (PWH) have increased cardiovascular events, inflammation, and high-risk coronary atherosclerosis. Statin therapy has been shown to lower the risk of cardiovascular disease (CVD) in the general population, but whether this results from reductions in coronary atherosclerosis and is mediated by decreased inflammation remains unknown. METHODS: REPRIEVE is a randomized, placebo-controlled trial of pitavastatin calcium (4 mg/day) vs. placeboenrolling at least 7500 PWH between 40-75 years, on antiretroviral therapy (ART), with low to moderate traditional CVD risk. The Mechanistic Substudy of REPRIEVE (A5333s) is co-enrolling 800 participants from 31 US sites. These participants undergo serial contrastenhanced coronary computed tomography angiography (CCTA) and measurements of biomarkers of inflammation and immune activation at baseline and after 2 years of follow-up. The primary objectives are to determine the effects of pitavastatin on noncalcified coronary atherosclerotic plaque (NCP) volume, low attenuation plaque, and positive remodeling and on changes in immune activation and inflammation and to assess relationships between the two. Changes in CAD will be assessed in a standardized fashion by a core lab with expert readers blinded to time points and participant information; immune activation and inflammation assessment is also performed centrally. RESULTS: To date the Mechanistic Substudy has completed planned enrollment, with 805 participants. CONCLUSION: This study represents the first large, randomized, CCTA-based assessment of the effects of a primary prevention strategy for CVD on high-risk CAD, immune activation and inflammation among PWH. The study will assess pitavastatin's effects on coronary plaque, and the interrelationship of these changes with biomarkers of immune activation and inflammation in PWH to determine mechanisms of CVD prevention and improved outcomes in this population.
RCT Entities:
BACKGROUND:People with HIV (PWH) have increased cardiovascular events, inflammation, and high-risk coronary atherosclerosis. Statin therapy has been shown to lower the risk of cardiovascular disease (CVD) in the general population, but whether this results from reductions in coronary atherosclerosis and is mediated by decreased inflammation remains unknown. METHODS: REPRIEVE is a randomized, placebo-controlled trial of pitavastatin calcium (4 mg/day) vs. placebo enrolling at least 7500 PWH between 40-75 years, on antiretroviral therapy (ART), with low to moderate traditional CVD risk. The Mechanistic Substudy of REPRIEVE (A5333s) is co-enrolling 800 participants from 31 US sites. These participants undergo serial contrast enhanced coronary computed tomography angiography (CCTA) and measurements of biomarkers of inflammation and immune activation at baseline and after 2 years of follow-up. The primary objectives are to determine the effects of pitavastatin on noncalcified coronary atherosclerotic plaque (NCP) volume, low attenuation plaque, and positive remodeling and on changes in immune activation and inflammation and to assess relationships between the two. Changes in CAD will be assessed in a standardized fashion by a core lab with expert readers blinded to time points and participant information; immune activation and inflammation assessment is also performed centrally. RESULTS: To date the Mechanistic Substudy has completed planned enrollment, with 805 participants. CONCLUSION: This study represents the first large, randomized, CCTA-based assessment of the effects of a primary prevention strategy for CVD on high-risk CAD, immune activation and inflammation among PWH. The study will assess pitavastatin's effects on coronary plaque, and the interrelationship of these changes with biomarkers of immune activation and inflammation in PWH to determine mechanisms of CVD prevention and improved outcomes in this population.
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