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Durable post-intervention control (PIC) of viraemia has been achieved in a subset of people following administration of\u00a0broadly neutralizing anti-HIV-1 antibodies (bNAb) and analytical interruption of\u00a0treatment\n                    <jats:sup>1\u20134<\/jats:sup>\n                    . Previous studies support a role for CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2009cells\u00a0in PIC\n                    <jats:sup>5\u20139<\/jats:sup>\n                    , but the precise features of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2009cells involved remain unclear. Here we mapped and functionally profiled CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2009cell responses to autologous HIV epitopes using longitudinal samples from four analytical treatment interruption trials in bNAb recipients. PIC was associated with superior pre-intervention HIV-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2009cell proliferative capacity, stem-cell-like memory phenotype and recall cytotoxicity against autologous HIV peptide-pulsed CD4\n                    <jats:sup>+<\/jats:sup>\n                    T\u2009cells. CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2009cell stemness was increased further following bNAb administration without emergence of new clonotypes targeting defined HLA-optimal epitopes. Multi-modal single-cell analyses revealed molecular features associated with PIC and HIV-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2009cell stemness, including signatures of metabolic fitness and reduced T\u2009cell exhaustion. These results identify immune features that precede subsequent PIC to inform the development of combination immunotherapies that will elicit durable HIV remission.\n                  <\/jats:p>","DOI":"10.1038\/s41586-025-09932-w","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T16:01:59Z","timestamp":1764604919000},"page":"196-204","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["CD8+ T cell stemness precedes post-intervention control of HIV viraemia"],"prefix":"10.1038","volume":"650","author":[{"given":"Zahra","family":"Kiani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0597-2848","authenticated-orcid":false,"given":"Jonathan M.","family":"Urbach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0329-4317","authenticated-orcid":false,"given":"Hannah","family":"Wisner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mpho J.","family":"Olatotse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8766-3768","authenticated-orcid":false,"given":"Daniel Y.","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua A.","family":"Acklin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicja","family":"Piechocka-Trocha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Bonheur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok","family":"Khatri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9865-8350","authenticated-orcid":false,"given":"Mathias","family":"Lichterfeld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3787-0259","authenticated-orcid":false,"given":"Jesper D.","family":"Gunst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9107-2023","authenticated-orcid":false,"given":"Ole S.","family":"S\u00f8gaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1727-8693","authenticated-orcid":false,"given":"Marina","family":"Caskey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0592-8564","authenticated-orcid":false,"given":"Michel C.","family":"Nussenzweig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6122-9245","authenticated-orcid":false,"given":"Bruce D.","family":"Walker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7903-346X","authenticated-orcid":false,"given":"David R.","family":"Collins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,1]]},"reference":[{"key":"9932_CR1","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1038\/s41586-018-0531-2","volume":"561","author":"P Mendoza","year":"2018","unstructured":"Mendoza, P. et al. Combination therapy with anti-HIV-1 antibodies maintains viral suppression. Nature 561, 479\u2013484 (2018).","journal-title":"Nature"},{"key":"9932_CR2","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1038\/s41586-022-04597-1","volume":"606","author":"C Gaebler","year":"2022","unstructured":"Gaebler, C. et al. Prolonged viral suppression with anti-HIV-1 antibody therapy. Nature 606, 368\u2013374 (2022).","journal-title":"Nature"},{"key":"9932_CR3","doi-asserted-by":"publisher","first-page":"2424","DOI":"10.1038\/s41591-022-02023-7","volume":"28","author":"JD Gunst","year":"2022","unstructured":"Gunst, J. D. et al. Early intervention with 3BNC117 and romidepsin at antiretroviral treatment initiation in people with HIV-1: a phase 1b\/2a, randomized trial. Nat. Med. 28, 2424\u20132435 (2022).","journal-title":"Nat. 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