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We quantified and compared expression levels of complement components (C2, C3a, C5a, C9), markers for coagulation (vWF-A2, ADAMTS13, tissue factor (TF), protein C, fibrinogen), and neutrophil activation (MPO, MMP-9) in plasma between virally suppressed PLWH (n\u2009=\u200940) and people living without HIV (PLWoH; n\u2009=\u200939). Platelet and activated platelet (CD62P+ cells) counts in the plasma samples were examined by flow cytometry analysis. To determine whether PLWH\u2019s plasma promotes neutrophil extracellular traps (NETs) and whether C2 and C5a levels correlate with NET formation, an ex vivo NET assay was performed. PLWH showed significantly altered C2 and C5a levels in plasma that correlated strongly with protein C and MPO. C2 also showed a positive correlation with proinflammatory markers (SSA, SAP, IL-1\u03b2, and VEGF). Furthermore, HIV status was a significant predictor of C2 and C5a levels. CD62P expression on platelets was significantly increased in PLWH. In addition, treatment of healthy neutrophils with PLWH\u2019s plasmapromoted NET formation, and this effect was inhibited by C5aR antibody treatment and platelet removal. These data suggest that activated platelets and soluble factors, such as higher C5a levels, contribute to NET formation in PLWH. Our findings provide evidence of complement dysregulation associated with inflammation and coagulation in PLWH. Altered soluble factors and platelet activation promote NET formation, potentially driving age-related non-AIDS comorbidities (NACMs).<\/jats:p>","DOI":"10.1093\/jimmun\/vkaf227","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T20:59:00Z","timestamp":1758315540000},"page":"2871-2880","source":"Crossref","is-referenced-by-count":5,"title":["Dysregulation of complement components associated with inflammation and coagulation in virally suppressed people living with HIV"],"prefix":"10.1093","volume":"214","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5096-7983","authenticated-orcid":false,"given":"Natalie T","family":"Subia","sequence":"first","affiliation":[{"name":"Department of Tropical Medicine, Medical Microbiology, and Pharmacology, John A. Burns School Medicine, University of Hawai\u2019i at M\u0101noa , Honolulu, HI 96813,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas K","family":"Awamura","sequence":"additional","affiliation":[{"name":"Department of Tropical Medicine, Medical Microbiology, and Pharmacology, John A. Burns School Medicine, University of Hawai\u2019i at M\u0101noa , Honolulu, HI 96813,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8699-0513","authenticated-orcid":false,"given":"Logan S","family":"Dean","sequence":"additional","affiliation":[{"name":"Department of Tropical Medicine, Medical Microbiology, and Pharmacology, John A. Burns School Medicine, University of Hawai\u2019i at M\u0101noa , Honolulu, HI 96813,","place":["United States"]},{"name":"Hawaii Center for AIDS, University of Hawai\u2019i at M\u0101noa , M\u0101noa, HI 96813,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keona","family":"Loftis","sequence":"additional","affiliation":[{"name":"Department of Tropical Medicine, Medical Microbiology, and Pharmacology, John A. Burns School Medicine, University of Hawai\u2019i at M\u0101noa , Honolulu, HI 96813,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6714-9294","authenticated-orcid":false,"given":"Louie Mar","family":"Gangcuangco","sequence":"additional","affiliation":[{"name":"Hawaii Center for AIDS, University of Hawai\u2019i at M\u0101noa , M\u0101noa, HI 96813,","place":["United States"]},{"name":"Department of Medicine, John A. Burns School of Medicine, University of Hawai\u2019i at M\u0101noa , Honolulu, HI 96813,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain","family":"MacPherson","sequence":"additional","affiliation":[{"name":"Department of Tropical Medicine, Medical Microbiology, and Pharmacology, John A. Burns School Medicine, University of Hawai\u2019i at M\u0101noa , Honolulu, HI 96813,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8535-964X","authenticated-orcid":false,"given":"Sandra","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Tropical Medicine, Medical Microbiology, and Pharmacology, John A. Burns School Medicine, University of Hawai\u2019i at M\u0101noa , Honolulu, HI 96813,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7395-038X","authenticated-orcid":false,"given":"Dominic C","family":"Chow","sequence":"additional","affiliation":[{"name":"Hawaii Center for AIDS, University of Hawai\u2019i at M\u0101noa , M\u0101noa, HI 96813,","place":["United States"]},{"name":"Department of Medicine, John A. Burns School of Medicine, University of Hawai\u2019i at M\u0101noa , Honolulu, HI 96813,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia M","family":"Shikuma","sequence":"additional","affiliation":[{"name":"Department of Tropical Medicine, Medical Microbiology, and Pharmacology, John A. Burns School Medicine, University of Hawai\u2019i at M\u0101noa , Honolulu, HI 96813,","place":["United States"]},{"name":"Hawaii Center for AIDS, University of Hawai\u2019i at M\u0101noa , M\u0101noa, HI 96813,","place":["United States"]},{"name":"Department of Medicine, John A. Burns School of Medicine, University of Hawai\u2019i at M\u0101noa , Honolulu, HI 96813,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9873-0137","authenticated-orcid":false,"given":"Juwon","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Tropical Medicine, Medical Microbiology, and Pharmacology, John A. 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