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- Title
Increased Macrophage-Specific Arterial Infiltration Relates to Noncalcified Plaque and Systemic Immune Activation in People With Human Immunodeficiency Virus.
- Authors
Toribio, Mabel; Wilks, Moses Q; Hedgire, Sandeep; Lu, Michael T; Cetlin, Madeline; Wang, Melissa; Alhallak, Iad; Durbin, Claudia G; White, Kevin S; Wallis, Zoey; Schnittman, Samuel R; Stanley, Takara L; El-Fakhri, Georges; Lee, Hang; Autissier, Patrick; Zanni, Markella V; Williams, Kenneth C; Grinspoon, Steven K
- Abstract
<bold>Background: </bold>Persistent immune activation is thought to contribute to heightened atherosclerotic cardiovascular disease (ASCVD) risk among people with human immunodeficiency virus (PWH).<bold>Methods: </bold>Participants (≥18 years) with or without human immunodeficiency virus (HIV) and without history of clinical ASCVD were enrolled. We hypothesized that increased macrophage-specific arterial infiltration would relate to plaque composition and systemic immune activation among PWH. We applied a novel targeted molecular imaging approach (technetium-99m [99mTc]-tilmanocept single photon emission computed tomography [SPECT]/CT) and comprehensive immune phenotyping.<bold>Results: </bold>Aortic 99mTc-tilmanocept uptake was significantly higher among PWH (n = 20) than participants without HIV (n = 10) with similar 10-year ASCVD risk (P = .02). Among PWH, but not among participants without HIV, noncalcified aortic plaque volume related directly to aortic 99mTc-tilmanocept uptake at different uptake thresholds. An interaction (P = .001) was seen between HIV status and noncalcified plaque volume, but not calcified plaque (P = .83). Systemic levels of caspase-1 (P = .004), CD14-CD16+ (nonclassical/patrolling/homing) monocytes (P = .0004) and CD8+ T cells (P = .005) related positively and CD4+/CD8+ T-cell ratio (P = .02) inversely to aortic 99mTc-tilmanocept uptake volume.<bold>Conclusions: </bold>Macrophage-specific arterial infiltration was higher among PWH and related to noncalcified aortic plaque volume only among PWH. Key systemic markers of immune activation relating to macrophage-specific arterial infiltration may contribute to heightened ASCVD risk among PWH.<bold>Clinical Trials Registration: </bold>NCT02542371.
- Subjects
SINGLE-photon emission computed tomography; HIV; CLINICAL trial registries; HIV infections; MACROPHAGES; ATHEROSCLEROSIS; RESEARCH funding
- Publication
Journal of Infectious Diseases, 2022, Vol 226, Issue 10, p1823
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiac301