• Chang-Yi Wang, Wing-Wai Wong, Hung-Chin Tsai, Yen-Hsu Chen, Be-Sheng Kuo, Shugene Lynn, Jana Blazkova, Katherine E Clarridge, Hsiao-Wen Su, Chia-Ying Lin, Fan-Chen Tseng, Annie Lai, Fu-Hung Yang, Chen-Han Lin, William Tseng, Hsiao-Yi Lin, Connie L Finstad, Flossie Wong-Staal, Carl V Hanson, Tae-Wook Chun, and Mei-June Liao.
• From United Biomedical, Hauppauge, NY (C.-Y.W., B.-S.K., C.L.F., F.W.-S.); United Biomedical Asia (C.-Y.W., S.L.) and United BioPharma (C.-Y.W., B.-S.K., H.-W.S., C.-Y.L., F.-C.T., A.L., F.-H.Y., C.-H.L., W.T., M.-J.L.), Hsinchu, Taipei Veterans General Hospital, Taipei (W.-W.W., H.-Y.L.), and Kaohsiung Veterans General Hospital (H.-C.T.) and Kaohsiung Medical University Hospital (Y.-H.C.), Kaohsiung - all in Taiwan; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (J.B., K.E.C., T.-W.C.); and the California Department of Public Health, Richmond (C.V.H.).
• N. Engl. J. Med. 2019 Apr 18; 380 (16): 1535-1545.

BackgroundAdministration of a single broadly neutralizing human immunodeficiency virus (HIV)-specific antibody to HIV-infected persons leads to the development of antibody-resistant virus in the absence of antiretroviral therapy (ART). It is possible that monotherapy with UB-421, an antibody that blocks the virus-binding site on human CD4+ T cells, could induce sustained virologic suppression without induction of resistance in HIV-infected persons after analytic treatment interruption.MethodsWe conducted a nonrandomized, open-label, phase 2 clinical study evaluating the safety, pharmacokinetics, and antiviral activity of UB-421 monotherapy in HIV-infected persons undergoing analytic treatment interruption. All the participants had undetectable plasma viremia (<20 copies of HIV RNA per milliliter) at the screening visit. After discontinuation of ART, participants received eight intravenous infusions of UB-421, at a dose of either 10 mg per kilogram of body weight every week (Cohort 1) or 25 mg per kilogram every 2 weeks (Cohort 2). The primary outcome was the time to viral rebound (≥400 copies per milliliter).ResultsA total of 29 participants were enrolled, 14 in Cohort 1 and 15 in Cohort 2. Administration of UB-421 maintained virologic suppression (<20 copies per milliliter) in all the participants (94.5% of measurements at study visits 2 through 9) during analytic treatment interruption, with intermittent viral blips (range, 21 to 142 copies per milliliter) observed in 8 participants (28%). No study participants had plasma viral rebound to more than 400 copies per milliliter. CD4+ T-cell counts remained stable throughout the duration of the study. Rash, mostly of grade 1, was a common and transient adverse event; one participant discontinued the study drug owing to a rash. A decrease in the population of CD4+ regulatory T cells was observed during UB-421 monotherapy.ConclusionsUB-421 maintained virologic suppression (during the 8 to 16 weeks of study) in participants in the absence of ART. One participant discontinued therapy owing to a rash. (Funded by United Biomedical and others; ClinicalTrials.gov number, NCT02369146.).Copyright © 2019 Massachusetts Medical Society.

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