{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:28:18Z","timestamp":1786321698129,"version":"build-2736575974"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI24CIII\/00003"],"award-info":[{"award-number":["PI24CIII\/00003"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chronic inflammation driven by microbial translocation is implicated in the increased risk of skeletal-related events (SREs) among people with HIV (PWH) on antiretroviral therapy (ART). We aimed to assess the association between plasma biomarkers of gut barrier dysfunction and incident SREs in PWH on suppressive ART, and whether the host\u2019s baseline immune status modifies this association. We employed a nested case-cohort design within the Spanish CoRIS cohort. We quantified baseline plasma markers (zonulin-1, LPS, LBP, and flagellin) in 65 incident SRE cases and a randomly selected subcohort of 263 PWH. Borgan II-weighted Cox regression models were used to test for associations and interactions between log2-transformed biomarkers and baseline CD4+ T-cell counts (&amp;lt; 500 vs \u2265 500 cells\/mm\u00b3). In the overall population, zonulin-1 was not significantly associated with SRE risk (aHR 1.54; 95% CI, 0.90-2.62). However, we detected a significant interaction between zonulin-1 and immune status (interaction p\u2009&amp;lt;\u2009.001). In participants with suboptimal immune recovery (CD4+ &amp;lt;500 cells\/mm\u00b3), higher zonulin-1 levels were associated with incident SREs (aHR 5.14; 95% CI, 2.25-11.77; interaction q\u2009&amp;lt;\u2009.001). Conversely, this association was absent in participants with preserved immune status (CD4+ \u2265500 cells\/mm\u00b3; aHR 0.98; 95% CI, 0.58-1.67). LPS, LBP, and flagellin showed no association with SREs regardless of immune status. Gut barrier dysfunction, measured by plasma zonulin-1, is associated with a higher risk of SREs; however, this association is restricted to PWH with incomplete immune reconstitution. These findings support a \u201ctwo-hit\u201d model in which immune competence and aging modulate the skeletal consequences of gut leakage.<\/jats:p>","DOI":"10.1093\/gerona\/glag186","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T11:32:01Z","timestamp":1784633521000},"source":"Crossref","is-referenced-by-count":0,"title":["Immune status modifies the association between plasma zonulin-1 and skeletal-related events in treated HIV: a case-cohort study"],"prefix":"10.1093","volume":"81","author":[{"given":"Carlos","family":"Pita-Mart\u00ednez","sequence":"first","affiliation":[{"name":"Unidad de Infecci\u00f3n Viral e Inmunidad, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III , Majadahonda, Madrid,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III , Madrid,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Rava","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III , Madrid,","place":["Spain"]},{"name":"Unidad de Coordinaci\u00f3n de CoRIS, Centro Nacional de Epidemiolog\u00eda, Instituto de Salud Carlos III , Madrid,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Mu\u00f1oz-Gomez","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III , Madrid,","place":["Spain"]},{"name":"Unidad de Enfermedades Infecciosas, Hospital Cl\u00ednico San Carlos , IdiSSC, Madrid,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melchor","family":"Riera","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III , Madrid,","place":["Spain"]},{"name":"Servicio de Medicina Interna\u2014Infecciosas del Hospital Universitario Son Espases , Palma de Mallorca,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaquim","family":"Peraire","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III , Madrid,","place":["Spain"]},{"name":"Hospital Universitari Joan XXIII de Tarragona, Institut de Recerca Biom\u00e8dica Catalunya Sud, University Rovira i Virgili , Tarragona,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Novella-Mena","sequence":"additional","affiliation":[{"name":"Servicio de Medicina Interna. Hospital Universitario Pr\u00edncipe de Asturias , Alcal\u00e1 de Henares, Madrid,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Guill\u00e9n Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Unidad de Medicina Interna Infecciosas. Hospital General Universitario Santa Luc\u00eda , Cartagena, Espa\u00f1a"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Montero-Alonso","sequence":"additional","affiliation":[{"name":"Unidad de Enfermedades Infecciosas. Servicio de Medicina Interna. Hospital Universitario y Polit\u00e9cnico la Fe , Valencia,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda \u00c1ngeles","family":"Jim\u00e9nez-Sousa","sequence":"additional","affiliation":[{"name":"Unidad de Infecci\u00f3n Viral e Inmunidad, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III , Majadahonda, Madrid,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III , Madrid,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8783-0450","authenticated-orcid":false,"given":"Salvador","family":"Resino","sequence":"additional","affiliation":[{"name":"Unidad de Infecci\u00f3n Viral e Inmunidad, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III , Majadahonda, Madrid,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III , Madrid,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6262-9344","authenticated-orcid":false,"given":"Rub\u00e9n","family":"Mart\u00edn-Escolano","sequence":"additional","affiliation":[{"name":"Unidad de Infecci\u00f3n Viral e Inmunidad, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III , Majadahonda, Madrid,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III , Madrid,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"CoRIS 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