{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T15:54:33Z","timestamp":1785772473510,"version":"3.56.0"},"reference-count":54,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"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":["Immunology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Despite the effectiveness of combined antiretroviral therapy (ART), HIV infection remains a chronic condition characterised by persistent inflammation and immune activation, likely associated with viral persistence and other factors such as cytomegalovirus (CMV) co\u2010infection. Long\u2010acting (LA) injectable formulations, a newer class of ART with improved and sustained bioavailability, may help modulate the HIV\u2010associated immunoinflammatory state. Therefore, we analysed dynamic changes in lymphoid immune\u2010activation and \u2010senescence markers in people with HIV (PWH) switching to LA injectable cabotegravir and rilpivirine (CAB\/RPV\u2010LA), compared with PWH who continued oral ART by choice. The relationship between CMV\u2010specific immune responses and phenotypic T\u2010cell alterations was also evaluated. T\u2010cell immune\u2010activation (CD38\u2009+\u2009HLA\u2010DR+) and \u2010senescence (CD28\u2010CD57+) were measured at baseline (T0), at 4 (T4), 28 (T28), 48 (T48) and at 72 (T72) weeks after switching to CAB\/RPV\u2010LA. A control group (CG) of PWH (PWH\u2010CG) on daily oral ART was studied at T0 and at 48\u2009weeks (T48). Furthermore, CMV\u2010specific cellular and humoral immune responses were assessed. Thirty\u2010seven PWH switching to CAB\/RPV\u2010LA and nine PWH\u2010CG were enrolled. In PWH\u2010LA, total CD4 levels remained stable over time, while CD8 levels decreased significantly at T72 versus T0 and T4. In CG, an increasing CD4 and decreasing CD8 trend was observed. The CD4\/CD8 ratio remained stable in both PWH\u2010LA and \u2010CG and showed a nonsignificant increase at T48 in PWH\u2010CG. Immune\u2010activation decreased in PWH\u2010LA: CD4 activation levels were significantly lower at T48 and T72 versus earlier time points and CD8 activation was reduced at T72 versus T0 and T4. Immune\u2010senescence declined in both compartments, with a significant reduction in CD8 senescence at T28, T48 and T72 compared to earlier time\u2010points. Delta analysis confirmed a greater reduction in immune\u2010activation and \u2010senescence in PWH\u2010LA compared to PWH\u2010CG. Regarding CMV immune response, anti\u2010CMV antibody levels remained stable with only a minor decline over time, whereas CMV\u2010specific T\u2010cell responses transiently increased at T28 before returning to baseline at T48 and T72. Switching to CAB\/RPV\u2010LA is associated with reduced T\u2010cell activation and senescence, particularly in CD8 T\u2010cell, suggesting improved immune homeostasis beyond viral suppression alone. However, despite these promising immunological changes, CMV coinfection remains a key driver of residual immune dysfunction.<\/jats:p>","DOI":"10.1111\/imm.70154","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T13:20:32Z","timestamp":1781616032000},"page":"138-148","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Long\u2010Acting Cabotegravir\/Rilpivirine Reduces Immune\u2010Activation and \u2010Senescence in People With\n                    <scp>HIV<\/scp>\n                    With\n                    <scp>CMV<\/scp>\n                    Co\u2010Infection"],"prefix":"10.1111","volume":"179","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5874-684X","authenticated-orcid":false,"given":"Mariasilvia","family":"Guardiani","sequence":"first","affiliation":[{"name":"Department of Public Health and Infectious Diseases Sapienza University of Rome  Rome Italy"},{"name":"Department of Neurosciences, Mental Health, and Sense Organs, NESMOS Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eeva","family":"Tortellini","sequence":"additional","affiliation":[{"name":"Department of Public Health and Infectious Diseases Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Carraro","sequence":"additional","affiliation":[{"name":"Department of Public Health and Infectious Diseases Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Antonella","family":"Zingaropoli","sequence":"additional","affiliation":[{"name":"Department of Public Health and Infectious Diseases Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Ansaldo","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit, SM Goretti Hospital Sapienza University of Rome  Latina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Grimaldi","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit, SM Goretti Hospital Sapienza University of Rome  Latina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Vita","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Mental Health, and Sense Organs, NESMOS Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Dominelli","sequence":"additional","affiliation":[{"name":"Department of Public Health and Infectious Diseases Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Mengoni","sequence":"additional","affiliation":[{"name":"Department of Public Health and Infectious Diseases Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Pasquazzi","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Mental Health, and Sense Organs, NESMOS Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ombretta","family":"Turriziani","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Rosa","family":"Ciardi","sequence":"additional","affiliation":[{"name":"Department of Public Health and Infectious Diseases Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Vullo","sequence":"additional","affiliation":[{"name":"Department of Public Health and Infectious Diseases Sapienza University of Rome  Rome 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