The research, appearing in The Journal of Infectious Diseases (PMID:35856671), was led by Principal Investigator Steven Grinspoon, MD, Chief of the Metabolism Unit at Mass General Hospital and Professor of Medicine at Harvard Medical School.
Persistent immune activation and downstream macrophage-specific arterial infiltration are thought to contribute to increased atherosclerotic (plaque) cardiovascular disease risk among people with HIV on anti-retroviral therapy.
In this study, Tc99m tilmanocept imaging was applied to investigate macrophage-specific arterial inflammation among participants with versus matched participants without HIV.
The hypothesis was that people with HIV would demonstrate higher levels of aortic arterial inflammation in relation to atherosclerotic plaque and immune activation.
Results showed that patients with HIV on antiretroviral therapy had significantly higher macrophage-specific arterial inflammation demonstrated by Tc99m tilmanocept than risk-matched people without HIV.
Total, non-calcified, and calcified aortic plaque volume calculated from CT scans did not differ significantly between groups.
Macrophage-specific arterial inflammation related to non-calcified plaque among HIV patients (and not among participants without HIV) and additionally related to levels of specific inflammatory markers.
Aortic Tc99m-tilmanocept uptake was significantly higher across different uptake thresholds among participants with HIV (P=0.03) and demonstrated a steeper relationship between arterial inflammation and non-calcified plaque volume (P=0.0001 for interaction between HIV-status and plaque volume) but not calcified plaque volume (P=0.83 for interaction).
Among people with HIV (and not among participants without HIV), non-calcified aortic plaque volume related directly with aortic Tc99m-tilmanocept uptake at different uptake thresholds.
Macrophage-specific arterial inflammation, quantified using a novel molecular imaging approach, was higher among patients with HIV on ART compared to matched participants of similar atherosclerotic cardiovascular risk without HIV.
Arterial inflammation related to non-calcified plaque volume only among patients with HIV.
Cellular biomarkers of inflammation also related to macrophage-specific arterial inflammation.
These key immune pathways may contribute to heightened cardiovascular disease risk among people with HIV and are thus of relevance to identifying novel therapies.
These data suggest increased macrophage-specific arterial inflammation of noncalcified plaque may be a mechanism of increased cardiovascular risk in people with HIV.
Use of Tc99m tilmanocept imaging may help to identify future targets for novel immunomodulatory therapies to reduce atherosclerotic cardiovascular disease risk among people with HIV on ART.
Navidea Biopharmaceuticals, Inc. (NYSE American: NAVB) is a biopharmaceutical company focused on the development of precision immunodiagnostic agents and immunotherapeutics.
Navidea is developing multiple precision-targeted products based on its Manocept platform to enhance patient care by identifying the sites and pathways of disease and enable better diagnostic accuracy, clinical decision-making, and targeted treatment.
Navidea's Manocept platform is predicated on the ability to specifically target the CD206 mannose receptor expressed on activated macrophages.
The Manocept platform serves as the molecular backbone of Tc99m tilmanocept, the first product developed and commercialized by Navidea based on the platform.
Navidea's strategy is to deliver superior growth and shareholder return by bringing to market novel products and advancing the company's pipeline through global partnering and commercialization efforts.
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