Increased Macrophage-Specific Arterial Infiltration Relates to Noncalcified Plaque and Systemic Immune Activation in People With Human Immunodeficiency Virus. (20th July 2022)

• Record Type: Journal Article
• 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
• Is Part Of: Journal of infectious diseases. Volume 226:Number 10(2022)
• Page Start: 1823
• Page End: 1833
• Publication Date: 2022-07-20
• Subjects: HIV -- tilmanocept -- arterial inflammation -- macrophages -- CD206 -- SPECT -- T-cell senescence -- caspase-1 -- NLRP3 inflammasome -- noncalcified plaque; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiac301
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: Background: Persistent immune activation is thought to contribute to heightened atherosclerotic cardiovascular disease (ASCVD) risk among people with human immunodeficiency virus (PWH). Methods: 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 [ 99m Tc]–tilmanocept single photon emission computed tomography [SPECT]/CT) and comprehensive immune phenotyping. Results: Aortic 99m Tc-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 99m Tc-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 99m Tc-tilmanocept uptake volume. Conclusions: 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. Clinical Trials Registration: NCT02542371. Abstract : CD206 + macrophage-specific arterial infiltration (via 99m Tc-tilmanocept SPECT/CT) was higher among participants with vs without HIV and relates to noncalcified plaque (and not calcified plaque) among people with HIV. NLRP3 inflammasome activation, nonclassical monocytes, and T-cell senescence related to CD206 + macrophage-specific arterial infiltration.