{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T13:08:58Z","timestamp":1779368938321,"version":"3.53.0"},"reference-count":22,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    People with HIV (PWH) on antiretroviral therapy (ART) exhibit a heightened risk of non\u2010AIDS\u2010defining cancers (NADCs), linked to chronic inflammation driven by microbial translocation. We investigated whether plasma biomarkers of gut barrier dysfunction are associated with NADC risk, hypothesizing this association is modified by immune status. We conducted a case\u2010cohort study nested within the Spanish CoRIS cohort. Plasma levels of zonulin\u20101, lipopolysaccharide, LPS\u2010binding protein, and flagellin were measured in 71 incident NADC cases and a 261\u2010individuals subcohort. Multivariable Cox proportional hazards models were used to estimate NADC risk, testing for effect modification by baseline CD4\u2009+\u2009T\u2010cell count. Zonulin\u20101 was not independently associated with NADC risk. However, a strong statistical interaction with baseline CD4\u2009+\u2009T\u2010cell count was detected (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.001). Among individuals with suboptimal immune recovery (defined as CD4\u2009+\u2009T\u2010cell count &lt;\u2009500 cells\/mm\u00b3), higher zonulin\u20101 levels were associated with a nearly threefold increased NADC risk (aHR\u2009=\u20092.94 (1.28\u20136.76)). Conversely, no association was observed in those with robust immune reconstitution (\u2265\u2009500 cells\/mm\u00b3; aHR=\u20090.84 (0.41\u20131.72)). Other biomarkers showed no association. This supports a \u201ctwo\u2010hit\u201d model of carcinogenesis where a compromised gut barrier and impaired immune competence are associated with an increased risk of cancer. Zonulin\u20101 is a key biomarker for identifying this high\u2010risk phenotype, suggesting targeted cancer prevention strategies restoring gut integrity.\n                  <\/jats:p>","DOI":"10.1002\/jmv.70884","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T13:23:51Z","timestamp":1774531431000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Elevated Zonulin\u20101 is Associated With an Increased Risk of Non\u2010AIDS\u2010Defining Cancers in People With HIV With Suboptimal Immune Recovery: A Case\u2010Cohort Study"],"prefix":"10.1002","volume":"98","author":[{"given":"Carlos","family":"Pita\u2010Mart\u00ednez","sequence":"first","affiliation":[{"name":"Unidad de Infecci\u00f3n Viral e Inmunidad, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, Majadahonda Madrid Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Mu\u00f1oz\u2010Garc\u00eda","sequence":"additional","affiliation":[{"name":"Unidad de Infecci\u00f3n Viral e Inmunidad, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, Majadahonda Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isidoro","family":"Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Unidad de Infecci\u00f3n Viral e Inmunidad, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, Majadahonda Madrid Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III Madrid 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 Spain"},{"name":"Centro Nacional de Epidemiolog\u00eda, Instituto de Salud Carlos III Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azucena","family":"Bautista Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III Madrid Spain"},{"name":"Servicio de Enfermedades Infecciosas, Hospital Universitario de Galdakao\u2010Usansolo Bizkaia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juncal","family":"P\u00e9rez\u2010Somarriba","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III Madrid Spain"},{"name":"Servicio de Enfermedades Infecciosas, Hospital Cl\u00ednico San Carlos Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoni","family":"Campins","sequence":"additional","affiliation":[{"name":"Servicio de Medicina Interna \u2010 Infecciosas. Hospital Universitario Son Espases. Instituto de Investigaci\u00f3n Sanitaria de las Islas Baleares (IdISBa) Palma de Mallorca 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 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Vera","sequence":"additional","affiliation":[{"name":"Servicio de Medicina Interna. Hospital General Universitario Santa Luc\u00eda Murcia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Montero\u2010Alonso","sequence":"additional","affiliation":[{"name":"Unidad de Enfermedades Infecciosas. Hospital Universitario y Polit\u00e9cnico la Fe, Instituto de Investigaci\u00f3n Sanitaria La Fe Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1945-6169","authenticated-orcid":false,"given":"Mar\u00eda \u00c1ngeles","family":"Jim\u00e9nez\u2010Sousa","sequence":"additional","affiliation":[{"name":"Unidad de Infecci\u00f3n Viral e Inmunidad, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, Majadahonda Madrid Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III Madrid 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 Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6262-9344","authenticated-orcid":false,"given":"Rub\u00e9n","family":"Mart\u00edn\u2010Escolano","sequence":"additional","affiliation":[{"name":"Unidad de Infecci\u00f3n Viral e Inmunidad, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, Majadahonda Madrid Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"CoRIS 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