{ "abstract": "Background\n\nPersistent immune dysregulation in people with HIV (PWH) on antiretroviral therapy (ART) contributes to an increased risk of skeletal-related events (SREs), serving as a critical paradigm for understanding accelerated aging and age-related diseases. We investigated the association between plasma biomarkers of immune regulation and senescence with incident SRE risk and evaluated potential effect modification by sex.Methods\n\nIn a case-cohort study nested within the Spanish CoRIS cohort (65 incident SRE cases; 252 subcohort, including 5 overlapping cases), we quantified 24 baseline biomarkers of immune checkpoints and senescence-associated secretory phenotype factors. We estimated adjusted hazard ratios (aHR) using Borgan II-weighted cause-specific Cox regression models adjusted for clinical confounders (age, region of origin, prior AIDS diagnosis, CD4 + T-cell count, coinfections, and lifestyle factors). Sex-biomarker interactions were assessed as exploratory endpoints.Results\n\nNineteen biomarkers were independently associated with increased SRE risk (p < 0.05 & q < 0.10). Angiogenic factors (VEGF-A; aHR = 1.94; 95% CI, 1.40-2.68), immune checkpoints (PD-L2; aHR = 1.95; 95% CI, 1.09-3.49), and tissue remodeling markers (MMP-1; aHR = 1.91; 95% CI, 1.08-3.39) displayed independent associations, alongside consistent signals for TIM-3, PD-L1, and IL-8. Pairwise correlation analysis demonstrated clustering between checkpoints and inflammatory cytokines. Exploratory interaction analysis indicated that sex modified these associations; signals for seven markers (e.g., IL-1α, VEGF-A) were stronger in females, although the limited number of events warrants caution.Conclusions\n\nCirculating biomarkers of immune exhaustion, inflammation, and senescence are independently associated with incident SREs in PWH on long-term ART. Our findings indicate a systemic pro-inflammatory signature and suggest that females exhibit higher sensitivity to inflammatory damage.", "abstract_shown": true, "affiliations": [ "Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, Spain.", "Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.", "Centro Nacional de Epidemiología (CNE), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.", "Servicio de Enfermedades Infecciosas. Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain.", "Universidad de Alcalá, Alcalá de Henares, Madrid, Spain.", "Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, Spain.", "Infectious Diseases Service, Hospital Universitario Marqués de Valdecilla- IDIVAL, Santander, Spain.", "Unidad de Enfermedades Infecciosas, Servicio de Medicina Interna del Complejo Hospitalario Universitario a Coruña (CHUAC), A Coruña, Spain.", "Grupo de Virología Clínica INIBIC-UDC, A Coruña, Spain.", "Servicio de Infecciosas. Hospital Universitari MutuaTerrassa, Terrassa, Barcelona, Spain.", "Servicio de Medicina Interna. Hospital Universitario Severo Ochoa. Leganés, Madrid, Spain.", "Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, Spain. sresino@isciii.es.", "Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. sresino@isciii.es.", "Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, Spain. r.martin@isciii.es.", "Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. r.martin@isciii.es." ], "article_type": "research article", "arxiv": null, "author_total": 14, "authors": [ { "affs": [ 0, 1 ], "name": "Carlos Pita-Martínez" }, { "affs": [ 1, 2 ], "name": "Marta Rava" }, { "affs": [ 0, 1 ], "name": "Ana Virseda-Berdices" }, { "affs": [ 0, 1 ], "name": "Isidoro Martínez" }, { "affs": [ 1, 3, 4 ], "name": "Santiago Moreno" }, { "affs": [ 1, 5 ], "name": "Carmen Elena Gómez Rodríguez" }, { "affs": [ 1, 6 ], "name": "Carlos Armiñanzas" }, { "affs": [ 7, 8 ], "name": "Álvaro Mena de Cea" }, { "affs": [ 9 ], "name": "Laura Gisbert Pérez" }, { "affs": [ 10 ], "name": "Rafael Rodríguez-Rosado" }, { "affs": [ 0, 1 ], "name": "María Ángeles Jiménez-Sousa" }, { "affs": [ 11, 12 ], "name": "Salvador Resino" }, { "affs": [ 13, 14 ], "name": "Rubén Martín-Escolano" }, { "name": "CoRIS cohort" } ], "bibtex": "https://research.draconitic.com/paper/3jrptfjs64ytd.bib", "cited_by": 0, "doi": "10.1186/s12979-026-00583-7", "fulltext_url": "https://europepmc.org/articles/PMC13689328", "id": "3jrptfjs64ytd", "issns": [ "1742-4933" ], "landing_url": "https://europepmc.org/article/MED/42907879", "language": "eng", "licence": "CC-BY-NC-ND", "licence_label": "CC BY-NC-ND", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/", "metadata_licence": null, "native_subjects": [ [ "lcc", "RC581-607" ], [ "lcc", "RC952-954.6" ], [ "openalex", "2711|HIV-related health complications and treatments" ] ], "openalex": "W7171363013", "pdf_url": "https://europepmc.org/articles/PMC13689328?pdf=render", "pmcid": "PMC13689328", "pmid": "42907879", "published": "2026-07-01", "publisher": "BMC", "ris": "https://research.draconitic.com/paper/3jrptfjs64ytd.ris", "sources": [ { "first_seen": "2026-10-30T12:19:57Z", "native_id": "MED:42907879", "source": "europepmc", "url": "https://europepmc.org/article/MED/42907879" }, { "first_seen": "2026-10-30T13:46:24Z", "native_id": "986f82080c9549ec8d40265dfa7ad434", "source": "doaj", "url": "https://doi.org/10.1186/s12979-026-00583-7" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2711|HIV-related health complications and treatments", "subfield": "general" } ], "title": "Plasma biomarkers of immune regulation and senescence are associated with incident skeletal-related events in people with HIV: a case-cohort study.", "title_text": "Plasma biomarkers of immune regulation and senescence are associated with incident skeletal-related events in people with HIV: a case-cohort study.", "type": "peer-reviewed", "updated_at": "2026-10-30T13:46:24Z", "url": "https://research.draconitic.com/paper/3jrptfjs64ytd", "venue": "Immunity & ageing : I & A", "versions": [] }