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Sixty-eight adult men living with human immunodeficiency virus (HIV), who were predominantly white and initiated antiretroviral therapy (ART) during primary or early-stage infection, underwent treatment interruption and were randomly assigned to a group receiving one or two doses of two long-acting broadly neutralizing antibodies (bNAbs) 3BNC117-LS and 10-1074-LS (arm A,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200934) or saline (arm B,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009= 34). The primary clinical study met its primary endpoint and was published elsewhere, demonstrating significantly delayed viral rebound and prolonged ART-free control in participants receiving bNAbs compared with placebo. The infusions were generally safe and well tolerated, with no study-related serious adverse events reported. The most common reported treatment-related adverse events were fatigue, lethargy and somnolence. Here we report on prespecified secondary analyses examining viral rebound, antibody sensitivity and reservoir dynamics, as well as prespecified exploratory analyses of rebound virus evolution and autologous antibody activity. Preinfusion reservoir measurements showed low levels of intact proviral HIV-1 DNA in circulating CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells in both arms. The rebounding viruses in participants who received the antibodies showed significant selection for resistance to 10-1074-LS but not to 3BNC117-LS. Notably, there was a significant correlation between greater initial reservoir sensitivity to autologous antibodies and 10-1074 and time to rebound. Finally, comparison of preinfusion and prerebound HIV-1 proviral reservoir showed a decrease in intact but not defective proviruses in arm A but not in arm B. Together, these findings suggest that baseline humoral immunity and prolonged exposure to LS-bNAbs jointly shape post-treatment viral rebound dynamics in individuals who initiate ART during primary infection. ClinicalTrials.gov identifier:\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\/ct2\/show\/NCT04319367\" ext-link-type=\"uri\">NCT04319367<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.1038\/s41591-026-04644-8","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T09:03:25Z","timestamp":1789463005000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Broadly neutralizing antibodies in adult males living with HIV undergoing analytical treatment interruption: secondary and exploratory outcomes of the phase II randomized controlled RIO trial"],"prefix":"10.1038","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0207-5423","authenticated-orcid":false,"given":"Marcilio 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J.","family":"Hernandez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christy","family":"Lavine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian M.","family":"Espinosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0271-0482","authenticated-orcid":false,"given":"Hanna","family":"Box","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6964-2042","authenticated-orcid":false,"given":"Emanuela","family":"Falaschetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise-Rae","family":"Cherrill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8232-9413","authenticated-orcid":false,"given":"Tamara","family":"Elliott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0583-8019","authenticated-orcid":false,"given":"Julie","family":"Fox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Pett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4632-2035","authenticated-orcid":false,"given":"Amanda","family":"Clarke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Uriel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9107-2023","authenticated-orcid":false,"given":"Ole","family":"Sogaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5214-9630","authenticated-orcid":false,"given":"Rebecca","family":"Sutherland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Boffito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Kinloch-Loes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6168-6745","authenticated-orcid":false,"given":"Chloe","family":"Orkin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3537-2432","authenticated-orcid":false,"given":"Simon","family":"Collins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiota","family":"Zacharopoulou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Robison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cintia","family":"Bittar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2654-0879","authenticated-orcid":false,"given":"Thiago","family":"Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Gazumyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mila","family":"Jankovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael 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Proviral latency, persistent human immunodeficiency virus infection, and the development of latency reversing agents. J. Infect. Dis. 215, S111\u2013S118 (2017).","journal-title":"J. Infect. Dis."},{"key":"4644_CR7","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/j.cell.2013.09.044","volume":"155","author":"DS Ruelas","year":"2013","unstructured":"Ruelas, D. S. & Greene, W. C. An integrated overview of HIV-1 latency. Cell 155, 519\u2013529 (2013).","journal-title":"Cell"},{"key":"4644_CR8","doi-asserted-by":"publisher","first-page":"15109","DOI":"10.1073\/pnas.96.26.15109","volume":"96","author":"RT Davey Jr.","year":"1999","unstructured":"Davey, R. T. Jr. et al. HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression. Proc. Natl Acad. Sci. USA 96, 15109\u201315114 (1999).","journal-title":"Proc. Natl Acad. Sci. 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