icon-    folder.gif   Conference Reports for NATAP  
  Conference on Retroviruses
and Opportunistic Infections
February 12-16, 2022
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Macrophage-specific arterial infiltration relates to plaque type and immune activation in HIV
  Mabel Toribio, MD
Massachusetts General Hospital
Boston, MA/ United States of America
program abstract

Persistent immune activation and downstream macrophage-specific arterial infiltration are thought to contribute to heightened atherosclerotic cardiovascular disease (ASCVD) risk among people with HIV (PWH) on ART. We applied a novel macrophage-specific imaging modality to investigate macrophage-specific infiltration among participants with vs without HIV in relation to atherosclerotic plaque and immune activation.
Twenty PWH on ART and 10 participants without HIV underwent systemic administration of the CD206 macrophage-specific radiotracer, 99mTc-tilmanocept, followed by SPECT/CT imaging to assess arterial inflammation. Participants were ≥18 yrs and without a history of symptomatic ASCVD. The volume of aortic tilmanocept uptake that was 3-6x background muscle activity (signal to background ratio, SBR) was measured. Aortic plaque volumes [total, non-calcified (Hounsfield units (HU) <130 and HU <300), and calcified plaque (HU≥130 and HU≥300)] were quantified using cardiac CT.
Participants with vs without HIV were similar in age (55.1 vs 58.4 yrs, P=0.12) and 10-yr ASCVD risk (7.3 vs. 8.1, P=0.70). Total, non-calcified, and calcified aortic plaque volume did not differ significantly between groups. Systemic markers of immune activation (caspase-1: P=0.01, MCP-1: P=0.02, and CXCL10: P=0.0004) and non-classical/homing monocytes (CD14-CD16+: P=0.02) were higher among PWH. Aortic tilmanocept uptake was higher across different uptake thresholds among PWH (P=0.03; Fig 1a-b). There was a significant interaction between HIV status and plaque volume in relation to arterial inflammation for non-calcified plaque (P=0.0001, Fig 1c) but not with calcified plaque (P=0.83) with significant relationships between non-calcified aortic plaque volume with each tilmanocept uptake threshold for PWH but not participants without HIV (Fig 1d). Markers of immune activation (sCD163 P=0.045 and caspase-1, P=0.02), immune cell subpopulations (CD14+CD16- P=0.0001, CD14+CD16+, P=0.02 and CD8+ T-cells P=0.01), and CD4+/CD8+ ratio (P=0.02) related to aortic tilmanocept uptake volume among PWH but not among participants without HIV.
These data applying a novel imaging modality provide unique evidence of macrophage-specific arterial inflammation among PWH on ART, which relates specifically to non-calcified plaque. Additionally, we characterize key immune pathways relating to increased arterial inflammation of relevance to identifying novel immunomodulatory therapies for CVD reduction.