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Here we conducted a first-in-human, phase 1 trial of the bispecific 10E8.4\/iMab antibody, which consists of a 10E8.4 arm binding the HIV-1 envelope glycoprotein membrane-proximal external region and an ibalizumab (iMab) arm binding the human CD4 molecule. 10E8.4\/iMab was administered intravenously (IV) or subcutaneously (SC). Safety\/tolerability within 2 weeks of 10E8.4\/iMab administration (primary outcome) and the pharmacokinetics (PK), antiviral activity, induction of anti-10E8.4\/iMab antibodies, longitudinal CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell counts and long-term safety (secondary outcomes) were evaluated. 54 participants living with HIV (PLWH) or without HIV (PLWoH) received 10E8.4\/iMab or placebo. In arm 1, PLWoH received 10E8.4\/iMab 0.3\u2009mg kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    IV, 1\u2009mg kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    SC, or 1\u2009mg kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    IV (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20093 each). In arm 2, PLWoH received 10E8.4\/iMab 3\u2009mg kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    IV, 10\u2009mg kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    IV or 30\u2009mg kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    IV (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20096 each). In arms 3\/3a, PLWH received 10E8.4\/iMab 10\u2009mg kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    IV (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20093) or 30\u2009mg kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    IV (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20096). In arm 4, PLWoH were randomized to receive 10E8.4\/iMab or placebo 2.5\u2009mg kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    SC or 10\u2009mg kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    SC (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20099 each). Participants in arms 1\u20133 were not randomized. No treatment-related serious adverse events (AEs) or AEs \u2265 grade\u20093 were reported. The most common solicited AEs were tenderness (10\/54, 18.5%), fatigue (18\/54, 33.3%) and headache (12\/54, 22.2%). Related grade 2 local and systemic solicited AEs occurred in one and six participants, respectively. Three of nine PLWH developed a generalized rash 8\u201312 days after infusion that resolved within 9\u201316 days. The primary objective of the study to evaluate the safety\/tolerability of 10E8.4\/iMab was met. These data support further study of 10E8.4\/iMab to expand HIV treatment and prevention options. ClinicalTrials.gov:\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT03875209\" ext-link-type=\"uri\">NCT03875209<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.1038\/s41591-026-04472-w","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T09:02:59Z","timestamp":1783414979000},"page":"2533-2545","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Bispecific 10E8.4\/iMab broadly neutralizing antibody in people with or without HIV-1: a partially randomized phase 1 trial"],"prefix":"10.1038","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8998-113X","authenticated-orcid":false,"given":"Deborah 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