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Combination therapy with anti-HIV-1 antibodies maintains viral suppression

Author

Listed:
  • Pilar Mendoza

    (The Rockefeller University)

  • Henning Gruell

    (Institute of Virology, University Hospital Cologne
    University Hospital Cologne
    partner site Bonn–Cologne)

  • Lilian Nogueira

    (The Rockefeller University)

  • Joy A. Pai

    (The Rockefeller University)

  • Allison L. Butler

    (The Rockefeller University)

  • Katrina Millard

    (The Rockefeller University)

  • Clara Lehmann

    (University Hospital Cologne
    partner site Bonn–Cologne
    Center for Molecular Medicine Cologne (CMMC), University of Cologne)

  • Isabelle Suárez

    (University Hospital Cologne
    partner site Bonn–Cologne
    Center for Molecular Medicine Cologne (CMMC), University of Cologne)

  • Thiago Y. Oliveira

    (The Rockefeller University)

  • Julio C. C. Lorenzi

    (The Rockefeller University)

  • Yehuda Z. Cohen

    (The Rockefeller University)

  • Christoph Wyen

    (University Hospital Cologne
    Praxis am Ebertplatz)

  • Tim Kümmerle

    (University Hospital Cologne
    Praxis am Ebertplatz)

  • Theodora Karagounis

    (The Rockefeller University)

  • Ching-Lan Lu

    (The Rockefeller University)

  • Lisa Handl

    (University of Tübingen)

  • Cecilia Unson-O’Brien

    (The Rockefeller University)

  • Roshni Patel

    (The Rockefeller University)

  • Carola Ruping

    (Institute of Virology, University Hospital Cologne)

  • Maike Schlotz

    (Institute of Virology, University Hospital Cologne)

  • Maggi Witmer-Pack

    (The Rockefeller University)

  • Irina Shimeliovich

    (The Rockefeller University)

  • Gisela Kremer

    (University Hospital Cologne)

  • Eleonore Thomas

    (University Hospital Cologne)

  • Kelly E. Seaton

    (Duke University)

  • Jill Horowitz

    (The Rockefeller University)

  • Anthony P. West

    (California Institute of Technology)

  • Pamela J. Bjorkman

    (California Institute of Technology)

  • Georgia D. Tomaras

    (Duke University
    Duke University
    Duke University
    Duke University)

  • Roy M. Gulick

    (Division of Infectious Diseases, Weill Cornell Medicine)

  • Nico Pfeifer

    (University of Tübingen
    University of Tübingen
    partner site Tübingen
    Max Planck Institute for Informatics)

  • Gerd Fätkenheuer

    (University Hospital Cologne
    partner site Bonn–Cologne)

  • Michael S. Seaman

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Florian Klein

    (Institute of Virology, University Hospital Cologne
    partner site Bonn–Cologne
    Center for Molecular Medicine Cologne (CMMC), University of Cologne)

  • Marina Caskey

    (The Rockefeller University)

  • Michel C. Nussenzweig

    (The Rockefeller University
    The Rockefeller University)

Abstract

Individuals infected with HIV-1 require lifelong antiretroviral therapy, because interruption of treatment leads to rapid rebound viraemia. Here we report on a phase 1b clinical trial in which a combination of 3BNC117 and 10-1074, two potent monoclonal anti-HIV-1 broadly neutralizing antibodies that target independent sites on the HIV-1 envelope spike, was administered during analytical treatment interruption. Participants received three infusions of 30 mg kg−1 of each antibody at 0, 3 and 6 weeks. Infusions of the two antibodies were generally well-tolerated. The nine enrolled individuals with antibody-sensitive latent viral reservoirs maintained suppression for between 15 and more than 30 weeks (median of 21 weeks), and none developed viruses that were resistant to both antibodies. We conclude that the combination of the anti-HIV-1 monoclonal antibodies 3BNC117 and 10-1074 can maintain long-term suppression in the absence of antiretroviral therapy in individuals with antibody-sensitive viral reservoirs.

Suggested Citation

  • Pilar Mendoza & Henning Gruell & Lilian Nogueira & Joy A. Pai & Allison L. Butler & Katrina Millard & Clara Lehmann & Isabelle Suárez & Thiago Y. Oliveira & Julio C. C. Lorenzi & Yehuda Z. Cohen & Chr, 2018. "Combination therapy with anti-HIV-1 antibodies maintains viral suppression," Nature, Nature, vol. 561(7724), pages 479-484, September.
    • Handle: RePEc:nat:nature:v:561:y:2018:i:7724:d:10.1038_s41586-018-0531-2
    DOI: 10.1038/s41586-018-0531-2
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    Citations

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    Cited by:

    1. Mathilde Foglierini & Pauline Nortier & Rachel Schelling & Rahel R. Winiger & Philippe Jacquet & Sijy O’Dell & Davide Demurtas & Maxmillian Mpina & Omar Lweno & Yannick D. Muller & Constantinos Petrov, 2024. "RAIN: machine learning-based identification for HIV-1 bNAbs," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Miriam Rosás-Umbert & Jesper D. Gunst & Marie H. Pahus & Rikke Olesen & Mariane Schleimann & Paul W. Denton & Victor Ramos & Adam Ward & Natalie N. Kinloch & Dennis C. Copertino & Tuixent Escribà & An, 2022. "Administration of broadly neutralizing anti-HIV-1 antibodies at ART initiation maintains long-term CD8+ T cell immunity," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Karunasinee Suphaphiphat & Delphine Desjardins & Valérie Lorin & Nastasia Dimant & Kawthar Bouchemal & Laetitia Bossevot & Maxence Galpin-Lebreau & Nathalie Dereuddre-Bosquet & Hugo Mouquet & Roger Gr, 2023. "Mucosal application of the broadly neutralizing antibody 10-1074 protects macaques from cell-associated SHIV vaginal exposure," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    4. Christoph Kreer & Cosimo Lupo & Meryem S. Ercanoglu & Lutz Gieselmann & Natanael Spisak & Jan Grossbach & Maike Schlotz & Philipp Schommers & Henning Gruell & Leona Dold & Andreas Beyer & Armita Nourm, 2023. "Probabilities of developing HIV-1 bNAb sequence features in uninfected and chronically infected individuals," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    5. Kim-Marie A. Dam & Christopher O. Barnes & Harry B. Gristick & Till Schoofs & Priyanthi N. P. Gnanapragasam & Michel C. Nussenzweig & Pamela J. Bjorkman, 2022. "HIV-1 CD4-binding site germline antibody–Env structures inform vaccine design," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

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