{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:02:51Z","timestamp":1790179371735,"version":"4.1.0"},"posted":{"date-parts":[[2025,11,6]]},"group-title":"HIV\/AIDS","reference-count":84,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["UM1 AI100663"],"award-info":[{"award-number":["UM1 AI100663"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01 AI129795"],"award-info":[{"award-number":["R01 AI129795"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["UM1 AI164565"],"award-info":[{"award-number":["UM1 AI164565"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["1P30 AI124414-01A1"],"award-info":[{"award-number":["1P30 AI124414-01A1"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["UM1 AI126620"],"award-info":[{"award-number":["UM1 AI126620"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["INV-008540"],"award-info":[{"award-number":["INV-008540"]}],"id":[{"id":"https:\/\/ror.org\/0456r8d26","id-type":"ROR","asserted-by":"publisher"}]},{"award":["INV-002705"],"award-info":[{"award-number":["INV-002705"]}],"id":[{"id":"https:\/\/ror.org\/0456r8d26","id-type":"ROR","asserted-by":"publisher"}]},{"award":["INV-036842"],"award-info":[{"award-number":["INV-036842"]}],"id":[{"id":"https:\/\/ror.org\/0456r8d26","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/0210rze73","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>RIO is an ongoing double blind randomized placebo controlled human trial in which participants that started 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 3BNC117-LS and 10-1074-LS (Arm A, n = 34), or saline (Arm B, n = 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 to placebo. The infusions were generally safe and well tolerated. Here we report on pre-specified secondary analyses examining viral rebound, antibody sensitivity, and reservoir dynamics, as well as exploratory analyses of rebound virus evolution and autologous antibody activity. Pre-infusion reservoir measurements showed low levels of intact proviral HIV-1 DNA in circulating CD4+ T cells in both arms. The rebounding viruses in participants that 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 to 10-1074 and time to rebound. Finally, comparison of pre-infusion and pre-rebound 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 may shape post-treatment viral rebound dynamics in individuals that initiate ART during primary infection.<\/jats:p>\n                <jats:p>\n                  <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                  identifier:\n                  <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04319367\">NCT04319367<\/jats:ext-link>\n                <\/jats:p>","DOI":"10.1101\/2025.11.03.25339415","type":"posted-content","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T17:50:15Z","timestamp":1762451415000},"source":"Crossref","is-referenced-by-count":12,"title":["Enhanced HIV-1 Control After Antibody Therapy is Associated with Autologous Antibodies and Reservoir Clearance in the RIO trial"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0207-5423","authenticated-orcid":false,"given":"Marcilio J.","family":"Fumagalli","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Immunology, The Rockefeller University, New York, NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Kaczynska","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, The Rockefeller University, New York, NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9098-0418","authenticated-orcid":false,"given":"Marius","family":"Allombert","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, The Rockefeller University, New York, NY USA"},{"name":"Humoral Immunology Unit, Institute Pasteur, Universit\u00e9 Paris Cit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1705-5388","authenticated-orcid":false,"given":"\u00c1gata","family":"Lopes-Ribeiro","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, The Rockefeller University, New York, NY USA"},{"name":"Laboratory of Basic and Applied Virology, Microbiology department, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0975-7187","authenticated-orcid":false,"given":"Mari\u00e2ngela","family":"de Oliveira Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, The Rockefeller University, New York, NY USA"},{"name":"Laboratory of Antigen Targeting to Dendritic Cells, Parasitology Department, University of S\u00e3o Paulo, S\u00e3o Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianna J.","family":"Hernandez","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, The Rockefeller University, New York, NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6135-0547","authenticated-orcid":false,"given":"Christy","family":"Lavine","sequence":"additional","affiliation":[{"name":"Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian M.","family":"Espinosa","sequence":"additional","affiliation":[{"name":"Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 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Differential decay of intact and defective proviral DNA in HIV-1-infected individuals on suppressive antiretroviral therapy. JCI Insight 5(2020).","DOI":"10.1172\/jci.insight.132997"},{"key":"2026092308203947000_2025.11.03.25339415v3.17","doi-asserted-by":"crossref","unstructured":"Cho, A. , et al. Longitudinal clonal dynamics of HIV-1 latent reservoirs measured by combination quadruplex polymerase chain reaction and sequencing. Proc Natl Acad Sci U S A 119(2022).","DOI":"10.1073\/pnas.2117630119"},{"key":"2026092308203947000_2025.11.03.25339415v3.18","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2651-8"},{"key":"2026092308203947000_2025.11.03.25339415v3.19","doi-asserted-by":"publisher","DOI":"10.1172\/JCI124291"},{"key":"2026092308203947000_2025.11.03.25339415v3.20","doi-asserted-by":"crossref","unstructured":"Huang, A.S. , et al. Integration features of intact latent HIV-1 in CD4+ T cell clones contribute to viral persistence. 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