Statin Effects on Pericoronary Adipose Tissue Density in People With HIV: Insights From the REPRIEVE Trial

Borek Foldyna¹, Ibrahim Hadzic², Thomas Mayrhofer³, Júlia Karády⁴, Jana Taron⁵, Márton Kolossváry⁶, Vineet K Raghu², Sara McCallum⁷, Kayla Paradis², Marissa R Diggs⁷, Sarah M Chu⁷, Alex B Lu⁷, Charurut Somboonwit⁸, Jose I Bernardino⁹, Michael P Dubé¹⁰, Craig A Sponseller¹¹, Markella V Zanni⁷, Gerald S Bloomfield¹², Carlos D Malvestutto¹³, Carl J Fichtenbaum¹⁴, Judith A Aberg¹⁵, Judith S Currier¹⁶, Heather J Ribaudo¹⁷, Pamela S Douglas¹⁸, Michael T Lu², Steven K Grinspoon⁷

Affiliations

¹ Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. Electronic address: bfoldyna@mgh.harvard.edu.
² Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
³ Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Center for Preventive Medicine and Digital Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
⁴ Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Department of Medicine, Boston Children's Hospital, Boston, Massachusetts, USA; Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
⁵ Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Department of Radiology, Medical Center, University of Freiburg, Faculty of Medicine, Freiburg, Germany.
⁶ Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
⁷ Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
⁸ University of South Florida, Tampa, Florida, USA.
⁹ HIV Unit, Internal Medicine Department, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain.
¹⁰ AIDS Healthcare Foundation and University of Southern California Keck School of Medicine, Los Angeles, California, USA.
¹¹ Kowa Pharmaceuticals America, Montgomery, Alabama, USA.
¹² Department of Medicine, Duke Global Health Institute and Duke Clinical Research Institute, Duke University, Durham, North Carolina, USA.
¹³ Division of Infectious Diseases, The Ohio State University Medical Center, Columbus, Ohio, USA.
¹⁴ Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
¹⁵ Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
¹⁶ Division of Infectious Diseases, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California, USA.
¹⁷ Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
¹⁸ Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.

PMID: 41324519
PMCID: PMC12766717
DOI: 10.1016/j.jcmg.2025.10.012

Statin Effects on Pericoronary Adipose Tissue Density in People With HIV: Insights From the REPRIEVE Trial

Borek Foldyna et al. JACC Cardiovasc Imaging. 2025.

. 2025 Nov 24:S1936-878X(25)00594-7.

doi: 10.1016/j.jcmg.2025.10.012. Online ahead of print.

Authors

Affiliations

¹ Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. Electronic address: bfoldyna@mgh.harvard.edu.
² Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
³ Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Center for Preventive Medicine and Digital Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
⁴ Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Department of Medicine, Boston Children's Hospital, Boston, Massachusetts, USA; Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
⁵ Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Department of Radiology, Medical Center, University of Freiburg, Faculty of Medicine, Freiburg, Germany.
⁶ Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
⁷ Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
⁸ University of South Florida, Tampa, Florida, USA.
⁹ HIV Unit, Internal Medicine Department, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain.
¹⁰ AIDS Healthcare Foundation and University of Southern California Keck School of Medicine, Los Angeles, California, USA.
¹¹ Kowa Pharmaceuticals America, Montgomery, Alabama, USA.
¹² Department of Medicine, Duke Global Health Institute and Duke Clinical Research Institute, Duke University, Durham, North Carolina, USA.
¹³ Division of Infectious Diseases, The Ohio State University Medical Center, Columbus, Ohio, USA.
¹⁴ Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
¹⁵ Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
¹⁶ Division of Infectious Diseases, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California, USA.
¹⁷ Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
¹⁸ Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.

PMID: 41324519
PMCID: PMC12766717
DOI: 10.1016/j.jcmg.2025.10.012

Abstract

Background: The effects of statin therapy on pericoronary adipose tissue (PCAT) and its relationship with plaque progression and outcomes in people with HIV (PWH) remain poorly understood.

Objectives: The aim of this study was to evaluate PCAT density changes over time; statin effects on PCAT; and associations among PCAT changes, coronary plaque, and clinical outcomes.

Methods: In the REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) mechanistic computed tomographic (CT) substudy (n = 753, mean age 51 ± 6 years, 17% women), PCAT density was measured from noncontrast CT images at baseline and 2 years, while coronary plaque volumes (total, calcified, and noncalcified) were assessed from contrast-enhanced CT angiograms. Analyses were stratified by coronary artery disease burden (segment involvement score 0, 1-3, or ≥4) and adjusted for technical parameters, atherosclerotic cardiovascular disease risk, body mass index, inflammatory biomarkers, and statin allocation. Associations among PCAT, plaque changes, and events (all-cause mortality, major adverse cardiovascular events [MACE], and MACE or death) were evaluated.

Results: Baseline PCAT density was -87.7 ± 10.5 HU, increasing by 4.5 HU (95% CI: 3.8-5.2; P < 0.001) over 2 years. Pitavastatin prevented this increase in participants with segment involvement scores ≥4 (-1.7 HU vs +3.8 HU; P = 0.016, pitavastatin vs placebo, respectively). Greater PCAT density was associated with higher noncalcified plaque volume (per +10 HU, +5.0 mm³; P = 0.075) and reduced calcified plaque progression (-3.2 mm³; P = 0.031). Over a median of 6.3 years, 4.2% of patients died. Baseline PCAT density was independently associated with all-cause mortality (HR per +10 HU: 1.95; 95% CI: 1.03-3.69; P = 0.040), but not MACE.

Conclusions: PCAT density increases over time in PWH, but pitavastatin mitigates this in those with high coronary artery disease burden. PCAT density is associated with vulnerable plaque morphology and all-cause mortality, supporting its potential as a prognostic imaging biomarker in PWH. (Randomized Trial to Prevent Vascular Events in HIV [REPRIEVE]; NCT02344290).

Keywords: coronary artery disease; coronary plaque; major adverse cardiovascular events; people with HIV.

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Conflict of interest statement

Funding Support and Author Disclosures This work was supported by National Heart, Lung, and Blood Institute (NHLBI) grant R01HL170877 (to Dr Foldyna) and the Nutrition Obesity Research Center at Harvard (grant P30DK040561 to Dr Grinspoon). This study was also supported through National Institutes of Health grants U01HL123336 and 1UG3HL164285 (to the Clinical Coordinating Center) and grants U01HL123339 and 1U24HL164284 (to the Data Coordinating Center), as well as funding from Kowa Pharmaceuticals America, Gilead Sciences, and ViiV Healthcare. The National Institute of Allergy and Infectious Diseases supported this study through grant UM1 AI068636, which supports the Advancing Clinical Therapeutics Globally Leadership and Operations Center, and grant UM1 AI106701, which supports the Advancing Clinical Therapeutics Globally Laboratory Center. The views expressed in this paper are those of the authors and do not necessarily represent the views of the NHLBI; the National Institute of Allergy and Infectious Diseases; the National Institutes of Health; or the U.S. Department of Health and Human Services. Dr Foldyna has received institutional research support from the NHLBI, AstraZeneca, MedImmune, Cleerly, and MedTrace, all outside of the submitted work. Dr Taron has received funding from Deutsche Forschungsgesellschaft (German Research Foundation) grant TA 1438/1–2. Dr Kolossváry has received consulting fees from Elucid, outside of the submitted work. Dr Raghu has received support from American Heart Association Career Development Award 935176 and NHLBI grant K01HL168231; and has stock holdings in NVIDIA, Alphabet, Apple, Amazon, and Meta. Dr Dubé has received personal fees from Gilead, ViiV Healthcare, and Merck Sharpe & Dohme, outside of the submitted work. Dr Sponseller is an employee of Kowa Pharmaceuticals America. Dr Zanni has received grant support through her institution from the National Institute of Allergy and Infectious Diseases and Gilead Sciences, relevant to the conduct of the study; has received grants from the National Institute of Allergy and Infectious Diseases and the NHLBI; has received support for attending the Conference on Retroviruses and Opportunistic Infections and the International Workshop on Women and HIV from conference organizing committees as an abstract reviewer and/or speaker; and is a member of data and safety monitoring boards for National Institutes of Health–funded studies, outside of the submitted work. Dr Malvestutto has received institutional research support from Eli Lilly; and has received personal fees from ViiV Healthcare and Gilead Sciences for participation in advisory board meetings, outside of the submitted work. Dr Fichtenbaum has received grant support through his institution from Gilead Sciences, ViiV Healthcare, GlaxoSmithKline, and Merck, all outside of the submitted work. Dr Aberg received grants from Massachusetts General Hospital during the conduct of the study; has received institutional research support for clinical trials from Gilead Sciences, GlaxoSmithKline, Janssen, MacroGenics, Merck, Pfizer, Regeneron, and ViiV Healthcare; has received personal fees for advisory board membership from GlaxoSmithKline/ViiV Healthcare, Invivyd, Merck, and Regeneron; and has been a data and safety monitoring board member for Kintor Pharmaceuticals, all outside of the submitted work. Dr Currier has received consulting fees from Merck. Dr Ribaudo received grants from the NHLBI and Kowa Pharmaceuticals during the conduct of this study; and has received grants from the National Institute of Allergy and Infectious Diseases, the NHLBI, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Institute on Aging, outside of the submitted work. Dr Lu has received grant support through his institution from the NHLBI and Kowa Pharmaceuticals America, for the conduct of the REPRIEVE trial; has received grant support from the American Heart Association, Amgen, AstraZeneca, Ionis, Johnson & Johnson Innovation, MedImmune, the National Academy of Medicine, the NHLBI, and the Risk Management Foundation of the Harvard Medical Institutions, outside of the submitted work. Dr Grinspoon has received grants from the National Institutes of Health, Kowa Pharmaceuticals, Gilead Sciences, and ViiV Healthcare during the conduct of the study; has received personal consulting fees from TheraTechnologies and ViiV Healthcare; and has served on scientific advisory boards for Marathon Asset Management and Exavir Therapeutics, all outside of the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

**FIGURE 1. Examples of Baseline and Follow-Up PCAT Measurements in REPRIEVE**
The figure demonstrates the change in pericoronary adipose tissue (PCAT) in a representative participant in the high coronary artery disease burden (segment involvement score ≥14) group, randomized to statin therapy, changing from −98 to −104 HU over 2 years of follow-up. CT= computed tomographic; REPRIEVE = Randomized Trial to Prevent Vascular Events in HIV.

**FIGURE 2. Association Between Baseline PCAT Density and Coronary Plaque Volumes**
Forest plots showing the associations of baseline pericoronary adipose tissue (PCAT) density (per 10 HU) with total, calcified, and noncalcified plaque volumes. Estimates represent regression coefficients with 95% CIs. Asterisks indicate significance levels: *P < 0.05 and **P < 0.01. Results are based on patients with measurable coronary artery plaque (n = 253). Model 1 was adjusted for technical parameters (PCAT image noise [SD] and epicardial adipose tissue volume); model 2 was adjusted for model 1 parameters plus atherosclerotic cardiovascular disease and body mass index; and model 3: was adjusted for model 2 parameters plus biomarkers (interleukin-6 and high-sensitivity C-reactive protein).

See this image and copyright information in PMC

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Statin Effects on Pericoronary Adipose Tissue Density in People With HIV: Insights From the REPRIEVE Trial

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Statin Effects on Pericoronary Adipose Tissue Density in People With HIV: Insights From the REPRIEVE Trial

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Conflict of interest statement

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