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This coinfection is associated with accelerated HIV-1 disease progression and reduced survival. However, the immunological and virological mechanisms driving this progression are incompletely understood. To address this knowledge gap, using pleural effusion samples from PLWH and TB, we investigated the HIV-1 genetic landscape and the anti-HIV-1 immune response impacted by a TB-associated microenvironment. Our results revealed an enrichment of genetically intact HIV-1 and impaired CD8+ T cell-mediated antiviral response at the site of HIV-1\/Mtb coinfection. These findings indicate that the TB-associated microenvironment promotes the persistence of cells infected with replication-competent HIV-1 by creating a niche of reduced antiviral immune pressure, potentially contributing to the worsened clinical outcomes observed in PLWH and TB.<\/jats:p>","DOI":"10.1101\/2025.10.14.682453","type":"posted-content","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:15:34Z","timestamp":1760573734000},"source":"Crossref","is-referenced-by-count":0,"title":["The tuberculosis-associated microenvironment promotes HIV-1 persistence by impairing CD8+ T cell-mediated viral control"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2652-4676","authenticated-orcid":false,"given":"Samantha","family":"Cronin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Simpson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Pereyra Casanova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josefina","family":"Marin Rojas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Freja","family":"Warner van Dijk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Fisher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zo\u00ef","family":"Vahlas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"O\u2019Neil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirstie","family":"Bertram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunok","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Turk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Florencia","family":"Quiroga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Kelleher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christel","family":"Verollet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7045-3572","authenticated-orcid":false,"given":"Luciana","family":"Balboa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Palmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel Alejandro","family":"Duette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.10.14.682453","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T09:49:13Z","timestamp":1768470553000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.10.14.682453"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,15]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1101\/2025.10.14.682453","relation":{},"subject":[],"published":{"date-parts":[[2025,10,15]]},"subtype":"preprint"}}