{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:54:58Z","timestamp":1790762098733,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,1,9]],"date-time":"2021-01-09T00:00:00Z","timestamp":1610150400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009139","name":"Deutsches Zentrum f\u00fcr Infektionsforschung","doi-asserted-by":"publisher","award":["80185MDCAH"],"award-info":[{"award-number":["80185MDCAH"]}],"id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009139","name":"Deutsches Zentrum f\u00fcr Infektionsforschung","doi-asserted-by":"publisher","award":["8018804915"],"award-info":[{"award-number":["8018804915"]}],"id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HIV Medicine"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>Despite its importance as an HIV anatomic sanctuary, little is known about the characteristics of the HIV reservoir in the terminal ileum (TI). In blood, the immune checkpoint inhibitor programmed\u2010death\u20101 (PD\u20101) has been linked to the HIV reservoir and T\u2010cell immune dysfunction. We thus evaluated PD\u20101 expression and cell\u2010associated HIV DNA in memory CD4 T\u2010cell subsets from TI, peripheral blood (PB) and rectum (RE) of untreated and treated HIV\u2010positive patients to identify associations between PD\u20101 and HIV reservoir in other sites.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using mononuclear cells from PB, TI and RE of untreated HIV\u2010positive (<jats:italic>N<\/jats:italic>\u00a0=\u00a06), treated (<jats:italic>n<\/jats:italic>\u00a0=\u00a018) HIV\u2010positive and uninfected individuals (<jats:italic>n<\/jats:italic>\u00a0=\u00a016), we identified and sorted distinct memory CD4 T\u2010cell subsets by flow cytometry, quantified their cell\u2010associated HIV DNA using quantitative PCR and assessed PD\u20101 expression levels using geometric mean fluorescence intensity. Combined HIV\u20101 RNA <jats:italic>in situ<\/jats:italic> hybridization and immunohistochemistry was performed on ileal biopsy sections.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Combined antiretroviral therapy (cART)\u2010treated patients with undetectable HIV RNA and significantly lower levels of HIV DNA in PB showed particularly high PD\u20101 expression in PB and TI, and high HIV DNA levels in TI, irrespective of clinical characteristics. By contrast, in treatment\u2010na\u00efve patients HIV DNA levels in memory CD4 T\u2010cell subsets were high in PB and TI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Elevated PD\u20101 expression on memory CD4 T\u2010cells in PB and TI despite treatment points to continuous immune dysfunction and underlines the importance of evaluating immunotherapy in reversing HIV latency and T\u2010cell reconstitution. As HIV DNA particularly persists in TI despite cART, investigating samples from TI is crucial in understanding HIV immunopathogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hiv.13031","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T01:09:22Z","timestamp":1610672962000},"page":"397-408","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["HIV DNA reservoir and elevated PD\u20101 expression of CD4\u00a0T\u2010cell subsets particularly persist in the terminal ileum of HIV\u2010positive patients despite cART"],"prefix":"10.1111","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8026-6495","authenticated-orcid":false,"given":"C","family":"Horn","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases Department I of Internal Medicine University of Cologne Cologne Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC) University of Cologne 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Faculty of Medicine and University Hospital of Cologne University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Knops","sequence":"additional","affiliation":[{"name":"Institute of Virology Faculty of Medicine and University Hospital of Cologne University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V","family":"Bondet","sequence":"additional","affiliation":[{"name":"Immunobiology of Dendritic Cells Unit Inserm U1223 Institut Pasteur Paris Cedex 15 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Duffy","sequence":"additional","affiliation":[{"name":"Immunobiology of Dendritic Cells Unit Inserm U1223 Institut Pasteur Paris Cedex 15 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