Proteomic Signature of Subclinical Coronary Artery Disease in People With HIV: Analysis of the REPRIEVE Mechanistic Substudy.

Background: People with HIV (PWH) have subclinical coronary artery disease (CAD) despite low traditional atherosclerotic cardiovascular disease (ASCVD) risk scores. Coronary plaque in PWH presents as a unique phenotype, but little is known about the contributions of specific inflammatory pathways to plaque phenotypes in PWH.
Methods: The REPRIEVE Mechanistic Substudy enrolled PWH on ART without known cardiovascular disease. We used a targeted discovery proteomics approach to evaluate 246 unique proteins representing cardiovascular, inflammatory, and immune pathways. Proteomic signatures were determined for presence of coronary artery calcium (CAC > 0) and presence of coronary plaque.
Results: Data were available for 662 participants (aged 51 [SD 6] years, ASCVD risk score 4.9% [SD 3.1%]). Among 12 proteins associated with both CAC and presence of coronary plaque, independent of ASCVD risk score, the odds ratios were highest for NRP1: 5.1 (95% confidence interval [CI], 2.3-11.4) for CAC and 2.9 (95% CI, 1.4-6.1) for presence of plaque. Proteins uniquely related to presence of plaque were CST3, LTBR, MEPE, PLC, SERPINA5, and TNFSF13B; in contrast, DCN, IL-6RA, OSMR, ST2, and VCAM1 were only related to CAC.
Conclusions: Distinct immune and inflammatory pathways are differentially associated with subclinical CAD phenotypes among PWH. This comprehensive set of targets should be further investigated to reduce atherosclerosis and ASCVD in PWH.
Clinical Trials Registration: NCT02344290.
Competing Interests: Potential conflicts of interest. M. T. L. reports grant support through his institution from Kowa Pharmaceuticals America, Inc for the conduct of the study; grant support from MedImmune/AstraZeneca; and personal fees from PQ Bypass outside of the current work. M. V. Z. reports grant support through her institution from NIH/NIAID and Gilead Sciences, Inc, relevant to the conduct of the study; and grants from NIH/NIAID and NIH/NHLBI outside the submitted work. H. R. reports grants from NIH/NIAID and NIH/NHLBI during the conduct of the study; and grants from NIH/NIAID, NIH/NHLBI, NIH/NIDDK, and NIH/NIA, outside the submitted work. A. C. reports grants from NIH/NIAID during the conduct of the study; and grants from NIH/NIAID outside the submitted work. C. F. reports grant support through his institution from Gilead Sciences, ViiV Healthcare, GSK, Janssen, Abbvie, Merck, Amgen, and Cytodyn outside the submitted work. E. T. O. reports grant support through his institution from NIH, Giliead, ViiV, and GSK; and personal fees from Merck, ViiV Healthcare, and Theratechnologies outside the submitted work. J. A. A. reports institutional research support for clinical trials from Atea, Emergent Biosolutions, Frontier Technologies, Gilead Sciences, Glaxo Smith Kline, Janssen, Merck, Pfizer, Regeneron, and ViiV Healthcare; and personal fees for advisory boards from Glaxo Smith Kline and Merck, all outside the submitted work. J. C. reports consulting fees from Merck and Resvirlogix. S. K. G. reports grant support through his institution from Kowa Pharmaceuticals America, Inc, Gilead Sciences, Inc, and ViiV for the conduct of the study; grants from Theratechnologies and Navidea; and personal fees from Theratechnologies for consulting and ViiV for consulting, all outside the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
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