Cytomegalovirus Immunoglobulin G (IgG) Titer and Coronary Artery Disease in People With Human Immunodeficiency Virus (HIV)

Author:

Schnittman Samuel R1ORCID,Lu Michael T2,Mayrhofer Thomas23,Burdo Tricia H4,Fitch Kathleen V5,McCallum Sara5,Fulda Evelynne S5,Zanni Markella V5,Foldyna Borek2ORCID,Malvestutto Carlos6ORCID,Fichtenbaum Carl J7,Aberg Judith A8,Bloomfield Gerald S9,Overton Edgar T10,Currier Judith11,Tebas Pablo12,Sha Beverly E13,Ribaudo Heather J14,Flynn Jacqueline M4,Douglas Pamela S15,Erlandson Kristine M16,Grinspoon Steven K5ORCID

Affiliation:

1. Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital , Boston, Massachusetts , USA

2. Cardiovascular Imaging Research Center, Massachusetts General Hospital , Boston, Massachusetts , USA

3. School of Business Studies, Stralsund University of Applied Sciences , Stralsund , Germany

4. Department of Microbiology, Immunology, and Inflammation and Center for Neuro-Virology and Gene Editing, Temple University Lewis Katz School of Medicine , Philadelphia, Pennsylvania , USA

5. Metabolism Unit, Massachusetts General Hospital , Boston, Massachusetts , USA

6. Division of Infectious Diseases, The Ohio State University Wexner Medical Center , Columbus, Ohio , USA

7. Division of Infectious Diseases, Department of Medicine, University of Cincinnati , Cincinnati, Ohio , USA

8. Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai , New York, New York , USA

9. Division of Cardiology, Department of Medicine and Duke Clinical Research Institute, Duke University , Durham, North Carolina , USA

10. Division of Infectious Diseases, University of Alabama at Birmingham , Birmingham, Alabama , USA

11. Division of Infectious Diseases, University of California at Los Angeles , Los Angeles, California , USA

12. Department of Medicine, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania , USA

13. Division of Infectious Diseases, Department of Internal Medicine, Rush University Medical Center , Chicago, Illinois , USA

14. Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health , Boston, Massachusetts , USA

15. Duke Clinical Research Institute, Duke University School of Medicine , Durham, North Carolina , USA

16. Division of Infectious Diseases, Department of Medicine, University of Colorado , Aurora, Colorado , USA

Abstract

Abstract Background Cytomegalovirus (CMV) infection is thought to result in increased immune activation in people with human immunodeficiency virus (HIV, PWH). Although some data have linked asymptomatic CMV infection to cardiovascular disease among PWH, it remains unknown whether CMV is associated with increased or high-risk coronary plaque. Methods The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) enrolled PWH aged 40–75 years on stable antiretroviral therapy (ART) with low-to-moderate atherosclerotic cardiovascular disease (ASCVD) risk. Among a subset of US REPRIEVE participants, coronary plaque was assessed by coronary computed tomography angiography. Here, we assessed the relationship between CMV immunoglobulin G (IgG) titer and (1) levels of immune activation, (2) inflammatory biomarkers, and (3) coronary plaque phenotypes at study entry. Results Of 672 participants, mean age was 51 years, 83% were men, median ASCVD risk score was 4.5%, and 66% had current CD4+ T-cell count ≥500 cells/mm3. Higher CMV IgG quartile group was associated with older age and lower current and nadir CD4+ T-cell counts. CMV IgG titer was associated with specific inflammatory biomarkers (sCD163, MCP-1, interleukin [IL]-6, hsCRP) in univariate analysis, but not after controlling for HIV-specific factors. In contrast, CMV IgG titer was not associated with coronary artery disease indexes, including presence of plaque, coronary artery calcium (CAC) score >0, vulnerable plaque presence, or Leaman score >5. Conclusions No meaningful association was seen between CMV IgG titer and coronary artery disease indexes among ART-treated PWH at study enrollment. Longitudinal assessments in REPRIEVE will determine the relationship of CMV IgG titer to plaque progression and cardiovascular events. Clinical Trials Registration NCT02344290.

Funder

National Institutes of Health

National Heart, Lung, and Blood Institute

REPRIEVE Clinical Coordinating Center

REPRIEVE Data Coordinating Center

KOWA Pharmaceuticals

Gilead Sciences

ViiV Healthcare

National Institute of Allergy and Infectious Diseases

AIDS Clinical Trials Group

Leadership and Operations Center

ACTG

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

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