Cytomegalovirus IgG is Associated With Physical Function But Not Muscle Density in People With HIV

Author:

Abidi Maheen Z.1ORCID,Umbleja Triin2,Overton Edgar T.3,Burdo Tricia4,Flynn Jacqueline M.4,Lu Michael T.5,Taron Jana56,Schnittman Samuel R.78,Fitch Kathleen V.8,Zanni Markella V.8,Fichtenbaum Carl J.9,Malvestutto Carlos10,Aberg Judith A.11,Fulda Evelynne S.8,Eckard Allison Ross12,Manne-Goehler Jennifer13,Tuan Jessica J.14,Ribaudo Heather J.2,Douglas Pamela S.15,Grinspoon Steven K.8,Brown Todd T.16,Erlandson Kristine M.1ORCID

Affiliation:

1. Division of Infectious Diseases, Department of Medicine, University of Colorado, Denver, CO;

2. Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA;

3. Division of Infectious Diseases, University of Alabama at Birmingham School of Medicine, Birmingham, AL;

4. Department of Microbiology, Immunology, and Inflammation and Center for Neurovirology and Gene Editing, Temple University Lewis Katz School of Medicine, Philadelphia, PA;

5. Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA;

6. Department of Radiology, Medical Center, University of Freiburg, Freiburg, Germany;

7. Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA;

8. Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA;

9. Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, OH;

10. Division of Infectious Diseases, Ohio State University Medical Center, Columbus, OH;

11. Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY;

12. Departments of Pediatrics and Medicine, Divisions of Infectious Diseases, Medical University of South Carolina, Charleston, SC;

13. Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA;

14. Division of Infectious Diseases, Yale University School of Medicine, New Haven, CT;

15. Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC; and

16. Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.

Abstract

Background: Cytomegalovirus (CMV) seropositivity is associated with poor outcomes, including physical function impairment, in people without HIV. We examined associations between CMV IgG titer and physical function in virologically suppressed people with HIV (PWH). Methods: REPRIEVE is a double-blind randomized trial evaluating pitavastatin for primary prevention of atherosclerotic cardiovascular disease in PWH. This analysis focused on participants enrolled in a substudy with additional biomarker testing, imaging [coronary CT angiography], and physical function measures at entry. CMV IgG was measured using quantitative enzyme immunoassay, physical function by Short Physical Performance Battery, and muscle density and area by CT. Associations between CMV IgG (risk factor) and outcomes were evaluated using the partial Spearman correlation and linear and log-binomial regression. Results: Among 717 participants, 82% male, the median CMV IgG was 2716 (Q1, Q3: 807, 6672) IU/mL, all above the limit of quantification. Among 631 participants with imaging, there was no association between CMV IgG and CT-based muscle density or area, controlling for age (r = −0.03 and r = −0.01, respectively; P ≥ 0.38). Among 161 participants with physical function data, higher CMV IgG was associated with poorer overall modified Short Physical Performance Battery score (P = 0.02), adjusted for age, nadir CD4, and high-sensitivity C-reactive protein. Conclusions: Higher CMV IgG titer was associated with poorer physical function, not explained by previous immune compromise, inflammation, or muscle density or area. Further mechanistic studies are needed to understand this association and whether CMV-specific therapy can affect physical function in PWH.

Publisher

Ovid Technologies (Wolters Kluwer Health)

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