2026-06-19T22:33:11Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/273812026-03-31T00:20:45Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19608col_20.500.12105_19609
Repisalud
author
Pita-Martínez, Carlos
author
Muñoz-García, Paula
author
Martinez, Isidoro
author
Rava, Marta
author
Bautista Hernández, Azucena
author
Pérez-Somarriba, Juncal
author
Campins, Antoni
author
Novella Mena, María
author
Vera, Francisco
author
Montero-Alonso, Marta
author
Jimenez-Sousa, Maria Angeles
author
Resino, Salvador
author
Martín-Escolano, Rubén
author
CoRIS cohort
funder
Instituto de Salud Carlos III
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Agencia Estatal de Investigación (España)
funder
Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas)
funder
Comunidad de Madrid (España)
funder
Centro de Investigación Biomédica en Red - CIBERBBN (Bioingeniería, Biomateriales y Nanomedicina)
2026-03-30T17:52:19Z
2026-03-30T17:52:19Z
2026-04
C.Pita-Martínez, P.Muñoz-García, I.Martínez, et al., “Elevated Zonulin-1 is Associated With an Increased Risk of Non-AIDS-Defining Cancers in People With HIV With Suboptimal Immune Recovery: A Case-Cohort Study,” Journal of Medical Virology98 (2026): e70884. https://doi.org/10.1002/jmv.70884.
10.1002/jmv.70884
Journal of Medical Virology
41885575
https://hdl.handle.net/20.500.12105/27381
People with HIV (PWH) on antiretroviral therapy (ART) exhibit a heightened risk of non-AIDS-defining 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-cohort study nested within the Spanish CoRIS cohort. Plasma levels of zonulin-1, lipopolysaccharide, LPS-binding protein, and flagellin were measured in 71 incident NADC cases and a 261-individuals subcohort. Multivariable Cox proportional hazards models were used to estimate NADC risk, testing for effect modification by baseline CD4 + T-cell count. Zonulin-1 was not independently associated with NADC risk. However, a strong statistical interaction with baseline CD4 + T-cell count was detected (p = 0.001). Among individuals with suboptimal immune recovery (defined as CD4 + T-cell count < 500 cells/mm³), higher zonulin-1 levels were associated with a nearly threefold increased NADC risk (aHR = 2.94 (1.28-6.76)). Conversely, no association was observed in those with robust immune reconstitution (≥ 500 cells/mm³; aHR= 0.84 (0.41-1.72)). Other biomarkers showed no association. This supports a "two-hit" model of carcinogenesis where a compromised gut barrier and impaired immune competence are associated with an increased risk of cancer. Zonulin-1 is a key biomarker for identifying this high-risk phenotype, suggesting targeted cancer prevention strategies restoring gut integrity.
eng
CD4 + T‐cell
NADCs
PWH
Biomarkers
Microbial translocation
Zonulin‐1
Elevated Zonulin-1 is Associated With an Increased Risk of Non-AIDS-Defining Cancers in People With HIV With Suboptimal Immune Recovery: A Case-Cohort Study.
research article
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ElevatedZonulin‐1AssociatedIncreased_2026.pdf