. 2025 Apr 15;4(1):e001132.

doi: 10.1136/bmjmed-2024-001132. eCollection 2025.

Statins for primary prevention of cardiovascular events in people with HIV: target trial and modelling study

Henock G Yebyo¹, Huldrych F Guenthard^{2

3}, Eva A Rehfuess^{4

5}, Nicola Serra^{6

7}, Sarah R Haile¹, Oliver Senn⁸, Gregory M Lucas⁹, Oliver Langselius⁵, Jennifer E Thorne¹⁰, Vincent C Marconi¹¹, Sally B Coburn¹², Raynell Lang¹³, Jonathan A Colasanti¹⁴, Michael J Silverberg¹⁵, Sonia Napravnik¹⁶, Mona Loutfy¹⁷, Maile Karris¹⁸, Timothy R Sterling¹⁹, Greer A Burkholder²⁰, Keri N Althoff¹⁰, Milo A Puhan^{1

10}

Affiliations

¹ Epidemiology, Biostatistics, and Prevention Institute, University of Zurich, Zurich, Switzerland.
² Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
³ Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
⁴ Institute for Medical Information Processing, Biometry, and Epidemiology, Ludwig-Maximilians-Universität München, Munich, Germany.
⁵ Pettenkofer School of Public Health, Ludwig-Maximilians-Universität München, Munich, Germany.
⁶ Physics Institute, University of Zurich, Zurich, Switzerland.
⁷ European Organisation for Nuclear Research, Geneva, Switzerland.
⁸ Institute of Primary Care, University of Zurich and University Hospital Zurich, Zurich, Switzerland.
⁹ Division of Infectious Diseases, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
¹⁰ Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
¹¹ School of Medicine and Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
¹² Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
¹³ Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
¹⁴ Department of Medicine, Grady Health System, Emory University, Atlanta, Georgia, USA.
¹⁵ Division of Research, Kaiser Permanente, Oakland, California, USA.
¹⁶ Division of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
¹⁷ Maple Leaf Medical Clinic, Women's College Hospital, Toronto, Ontario, Canada.
¹⁸ Department of Medicine, University of California San Diego, La Jolla, California, USA.
¹⁹ Vanderbilt University Medical Center, Nashville, Tennessee, USA.
²⁰ Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, USA.

PMID: 40395649
PMCID: PMC12090529
DOI: 10.1136/bmjmed-2024-001132

Statins for primary prevention of cardiovascular events in people with HIV: target trial and modelling study

Henock G Yebyo et al. BMJ Med. 2025.

. 2025 Apr 15;4(1):e001132.

doi: 10.1136/bmjmed-2024-001132. eCollection 2025.

Authors

Affiliations

¹ Epidemiology, Biostatistics, and Prevention Institute, University of Zurich, Zurich, Switzerland.
² Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
³ Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
⁴ Institute for Medical Information Processing, Biometry, and Epidemiology, Ludwig-Maximilians-Universität München, Munich, Germany.
⁵ Pettenkofer School of Public Health, Ludwig-Maximilians-Universität München, Munich, Germany.
⁶ Physics Institute, University of Zurich, Zurich, Switzerland.
⁷ European Organisation for Nuclear Research, Geneva, Switzerland.
⁸ Institute of Primary Care, University of Zurich and University Hospital Zurich, Zurich, Switzerland.
⁹ Division of Infectious Diseases, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
¹⁰ Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
¹¹ School of Medicine and Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
¹² Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
¹³ Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
¹⁴ Department of Medicine, Grady Health System, Emory University, Atlanta, Georgia, USA.
¹⁵ Division of Research, Kaiser Permanente, Oakland, California, USA.
¹⁶ Division of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
¹⁷ Maple Leaf Medical Clinic, Women's College Hospital, Toronto, Ontario, Canada.
¹⁸ Department of Medicine, University of California San Diego, La Jolla, California, USA.
¹⁹ Vanderbilt University Medical Center, Nashville, Tennessee, USA.
²⁰ Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, USA.

PMID: 40395649
PMCID: PMC12090529
DOI: 10.1136/bmjmed-2024-001132

Erratum in

Correction: Statins for primary prevention of cardiovascular events in people with HIV: target trial and modelling study.
[No authors listed] [No authors listed] BMJ Med. 2025 Jul 7;4(1):e001132corr1. doi: 10.1136/bmjmed-2024-001132corr1. eCollection 2025. BMJ Med. 2025. PMID: 40735510 Free PMC article.

Abstract

Objective: To evaluate the effectiveness and benefit-harm balance of various statins for the primary prevention of cardiovascular disease in people with HIV.

Design: Target trial and modelling study.

Setting: North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), 1995 to 2019. NA-ACCORD integrates individual level data from >20 HIV cohorts across the US and Canada from people with HIV who have successfully linked into care.

Participants: 157 699 people with HIV enrolled in one of the cohorts of NA-ACCORD. 54 165 eligible individuals, aged 40-75 years, were enrolled in the target trial.

Main outcome measures: The primary outcomes for the target trial were the 10 year effects of statins on cardiovascular disease events (fatal and non-fatal myocardial infarction, hospital admission for unstable angina, coronary or arterial revascularisation, fatal and non-fatal stroke, or transient ischaemic attack) and harm outcomes (type 2 diabetes, mild cognitive impairment, rhabdomyolysis, and myopathy). The secondary outcome was the 10 year risk threshold where the reduction in cardiovascular disease outweighed the increased risk of harm outcomes, showing an overall net benefit of statins.

Results: Participants who first started receiving treatment with statins (statin initiators) had a 21% reduction in cardiovascular disease events (hazard ratio 0.79, 95% confidence interval (CI) 0.72 to 0.87) and a 26% reduction in the combined risk of stroke and myocardial infarction (0.74, 0.56 to 0.98), but a 12% increase in the risk of type 2 diabetes (1.12, 1.01 to 1.25) compared with participants who developed the indication but did not take statins (non-initiators). The effects on cognitive impairment (hazard ratio 1.13, 95% CI 0.82 to 1.56), myopathy (1.10, 0.76 to 1.61), and rhabdomyolysis (1.09, 0.68 to 1.75) were not statistically significant. On average, the benefit of statins exceeded harms for individuals with a 10 year baseline risk of cardiovascular disease of ≥13.8%. Subgroup specific thresholds included men (14.2%), women (11.1%), ages 40-64 years (13.8%) versus 65-75 years (15.1%), and CD4 count >200 cells/mm³ (13.6%) versus <200 cells/mm³ (15.3%). Varying weights for cardiovascular disease yielded thresholds ranging from 11.6% to 54.0%, whereas weights for harm outcomes resulted in thresholds ranging from 5.0% to >30.0%.

Conclusions: In this study, statins benefitted individuals with HIV with a moderate or high risk of cardiovascular disease, but the threshold for net benefit varied by patient subgroup and preference, implying the need to customise statin treatment to individual risks, preferences, and treatment goals. Given the limitations of observational data, further controlled studies are needed to evaluate the efficacy and safety of statins in people with HIV receiving modern antiretroviral therapy.

Keywords: Cardiology; Hiv; Preventive medicine.

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Conflict of interest statement

All authors have completed the ICMJE unifform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from Swiss National Science Foundation, National Institutes of Health (NIH), Centers for Disease Control and Prevention, Agency for Healthcare Research and Quality, Health Resources and Services Administration, Canadian Institutes of Health Research, National Institute of Allergy and Infectious Diseases (NIAID), National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Human Genome Research Institute (NHGRI), National Institute for Mental Health (NIMH), National Institute on Drug Abuse (NIDA), National Institute on Aging (NIA), National Institute of Dental and Craniofacial Research (NIDCR), National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Nursing Research (NINR), National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institute on Deafness and Other Communication Disorders. (NIDCD), and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) for the submitted work; funds from Merck Foundation, Gilead Sciences, ViiV Healthcare, Johnson and Johnson, Janssen, GSK and Novartis, Eli Lilly, Med-IQ, Bayer, NIH/NIAID, and TrioHealth that might have an interest in the submitted work in the previous three years; Coursera (five course specialisation), TrioHealth (advisory board), and NIH (consultation) that could appear to have influenced the submitted work; no financial relationships with any other organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Figures

Figure 1. 10 year cumulative incidence of cardiovascular disease events (fatal and non-fatal myocardial infarction, hospital admission for unstable angina, coronary or arterial revascularisation, fatal and non-fatal stroke, or transient ischaemic attack) and harm outcome events (type 2 diabetes, mild cognitive impairment, myopathy, and rhabdomyolysis) in participants who first started receiving statin treatment (statin initiators) and in those who developed the indication but did not take statins (non-initiators)

Figure 2. Distribution of benefit-harm balance across the baseline cardiovascular disease risk spectrum for all statins and for specific statins. Threshold for baseline cardiovascular disease risk, above which the prevention of cardiovascular disease outweighed the harmful outcomes, was 13.8% over 10 years (dotted lines)

See this image and copyright information in PMC

References

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Statins for primary prevention of cardiovascular events in people with HIV: target trial and modelling study

Affiliations

Statins for primary prevention of cardiovascular events in people with HIV: target trial and modelling study

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

Figures

References

Grants and funding

LinkOut - more resources

Full Text Sources

Research Materials