Clonal Hematopoiesis and Major Adverse Cardiac Events in People With HIV: Insights From the REPRIEVE Trial

Liying Xue, Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA (L.X., R. Bhattacharya, M.M.U., T.N., A.P., A.B., P.N.).
Romit Bhattacharya, Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA (L.X., R. Bhattacharya, M.M.U., T.N., A.P., A.B., P.N.).
Md Mesbah Uddin, Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA (L.X., R. Bhattacharya, M.M.U., T.N., A.P., A.B., P.N.).
Tetsushi Nakao, Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA (L.X., R. Bhattacharya, M.M.U., T.N., A.P., A.B., P.N.).
Roger Zou, Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston (R. Bhattacharya, T.N., R.Z., A.P., S.H., V.V., D.P., A.B., P.F., R. Bernardo, W.H., P.N.).
Aniruddh Patel, Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA (L.X., R. Bhattacharya, M.M.U., T.N., A.P., A.B., P.N.).
Sara Haidermota, Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston (R. Bhattacharya, T.N., R.Z., A.P., S.H., V.V., D.P., A.B., P.F., R. Bernardo, W.H., P.N.).
Abhishek Niroula, Cancer Program, Broad Institute, Cambridge, MA (A.N.).
Victoria Viscosi, Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston (R. Bhattacharya, T.N., R.Z., A.P., S.H., V.V., D.P., A.B., P.F., R. Bernardo, W.H., P.N.).
Darina Postupaka, Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston (R. Bhattacharya, T.N., R.Z., A.P., S.H., V.V., D.P., A.B., P.F., R. Bernardo, W.H., P.N.).
Aarushi Bhatnagar, Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA (L.X., R. Bhattacharya, M.M.U., T.N., A.P., A.B., P.N.).
Phoebe Finneran, Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston (R. Bhattacharya, T.N., R.Z., A.P., S.H., V.V., D.P., A.B., P.F., R. Bernardo, W.H., P.N.).
Rachel Bernardo, Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston (R. Bhattacharya, T.N., R.Z., A.P., S.H., V.V., D.P., A.B., P.F., R. Bernardo, W.H., P.N.).
Marissa R. Diggs, Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston. (M.R.D., K.V.F., S.M. C., S.M., M.V.Z., S.K.G.).
Kathleen V. Fitch, Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston. (M.R.D., K.V.F., S.M. C., S.M., M.V.Z., S.K.G.).
Sarah M. Chu, Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston. (M.R.D., K.V.F., S.M. C., S.M., M.V.Z., S.K.G.).
Sara McCallum, Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston. (M.R.D., K.V.F., S.M. C., S.M., M.V.Z., S.K.G.).
Judith S. Currier, Division of Infectious Diseases, David Geffen School of Medicine, University of California Los Angeles (J.S.C.).
Carl J. Fichtenbaum, Division of Infectious Diseases, University of Cincinnati College of Medicine, OH (C.J.F.).
Carlos D. Malvestutto, Division of Infectious Diseases, Ohio State University Medical Center, Columbus (C.D.M.).
Judith A. Aberg, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY (J.A.A.).
Gerald S. Bloomfield, Department of Medicine, Duke Global Health Institute and Duke Clinical Research Institute, Duke University, Durham, NC (G.S.B.).
Heather J. Ribaudo, Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA (H.J.R.).
Markella V. Zanni, Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston. (M.R.D., K.V.F., S.M. C., S.M., M.V.Z., S.K.G.).
Peter Libby, Department of Medicine, Harvard Medical School, Boston, MA (R. Bhattacharya, A.P., P.L., P.N.).
Whitney Hornsby, Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston (R. Bhattacharya, T.N., R.Z., A.P., S.H., V.V., D.P., A.B., P.F., R. Bernardo, W.H., P.N.).
Michael T. Lu, Department of Radiology, Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston. (M.T.L.).
Pamela S. Douglas, Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (P.S.D.).
Steven K. Grinspoon, Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston. (M.R.D., K.V.F., S.M. C., S.M., M.V.Z., S.K.G.).
Pradeep Natarajan, Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA (L.X., R. Bhattacharya, M.M.U., T.N., A.P., A.B., P.N.).

Document Type

Journal Article

Publication Date

11-6-2025

Journal

Arteriosclerosis, thrombosis, and vascular biology

DOI

10.1161/ATVBAHA.125.322896

Keywords

cardiovascular diseases; clonal hematopoiesis; myocardial infarction; pitavastatin; risk factors

Abstract

BACKGROUND: People with HIV (PWH) experience higher cardiovascular disease event rates not fully explained by traditional risk factors. Clonal hematopoiesis of indeterminate potential (CHIP), an emerging risk factor for cardiovascular disease in the general population, has been reported to be more prevalent in PWH. METHODS: Using high-coverage targeted CHIP sequencing in the REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) cardiovascular disease prevention trial, we investigated whether CHIP increases the risk of major adverse cardiovascular events (MACE) among PWH, as well as whether HIV-associated factors were associated with greater CHIP prevalence among PWH. We analyzed whole-exome and targeted sequencing from 4490 PWH without known cardiovascular disease; 1653 (36.8%) were female, and 2039 (45.4%) were Black. MACE was defined by including cardiovascular death, myocardial infarction, hospitalization for unstable angina, stroke, transient ischemic attack, peripheral artery disease, revascularization, or death from an undetermined cause. RESULTS: A total of 837 (18.6%) had CHIP driver mutations, with 385 (8.6%) at variant allele fraction ≥2% and 61 (1.4%) at variant allele fraction ≥10%. Although overall CHIP was not associated with MACE, the presence of large CHIP (variant allele fraction ≥10%) was associated with increased odds for the first occurrence of myocardial infarction or cardiac catheterization, or revascularization, despite low overall event rates. Adjustments for pitavastatin treatment did not attenuate this association. Furthermore, a larger CHIP clone size was associated with lower CD4 nadir and with increased risk of MACE. CONCLUSIONS: In PWH in the REPRIEVE trial who were low-to-moderate risk for incident cardiovascular disease, CHIP was not associated with increased prospective risk of MACE. However, a large CHIP was associated with increased risk of myocardial infarction and revascularization. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02344290.

Department

School of Medicine and Health Sciences Student Works

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