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Prolonged viral suppression with anti-HIV-1 antibody therapy

Author

Listed:
  • Christian Gaebler

    (The Rockefeller University)

  • Lilian Nogueira

    (The Rockefeller University)

  • Elina Stoffel

    (The Rockefeller University
    Columbia University Irving Medical Center)

  • Thiago Y. Oliveira

    (The Rockefeller University)

  • Gaëlle Breton

    (The Rockefeller University)

  • Katrina G. Millard

    (The Rockefeller University)

  • Martina Turroja

    (The Rockefeller University)

  • Allison Butler

    (The Rockefeller University)

  • Victor Ramos

    (The Rockefeller University)

  • Michael S. Seaman

    (Harvard Medical School)

  • Jacqueline D. Reeves

    (LabCorp)

  • Christos J. Petroupoulos

    (LabCorp)

  • Irina Shimeliovich

    (The Rockefeller University)

  • Anna Gazumyan

    (The Rockefeller University)

  • Caroline S. Jiang

    (The Rockefeller University)

  • Nikolaus Jilg

    (Massachusetts General Hospital)

  • Johannes F. Scheid

    (Massachusetts General Hospital)

  • Rajesh Gandhi

    (Massachusetts General Hospital)

  • Bruce D. Walker

    (MIT and Harvard)

  • Michael C. Sneller

    (National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH))

  • Anthony Fauci

    (National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH))

  • Tae-Wook Chun

    (National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH))

  • Marina Caskey

    (The Rockefeller University)

  • Michel C. Nussenzweig

    (The Rockefeller University
    The Rockefeller University)

Abstract

HIV-1 infection remains a public health problem with no cure. Anti-retroviral therapy (ART) is effective but requires lifelong drug administration owing to a stable reservoir of latent proviruses integrated into the genome of CD4+ T cells1. Immunotherapy with anti-HIV-1 antibodies has the potential to suppress infection and increase the rate of clearance of infected cells2,3. Here we report on a clinical study in which people living with HIV received seven doses of a combination of two broadly neutralizing antibodies over 20 weeks in the presence or absence of ART. Without pre-screening for antibody sensitivity, 76% (13 out of 17) of the volunteers maintained virologic suppression for at least 20 weeks off ART. Post hoc sensitivity analyses were not predictive of the time to viral rebound. Individuals in whom virus remained suppressed for more than 20 weeks showed rebound viraemia after one of the antibodies reached serum concentrations below 10 µg ml−1. Two of the individuals who received all seven antibody doses maintained suppression after one year. Reservoir analysis performed after six months of antibody therapy revealed changes in the size and composition of the intact proviral reservoir. By contrast, there was no measurable decrease in the defective reservoir in the same individuals. These data suggest that antibody administration affects the HIV-1 reservoir, but additional larger and longer studies will be required to define the precise effect of antibody immunotherapy on the reservoir.

Suggested Citation

  • Christian Gaebler & Lilian Nogueira & Elina Stoffel & Thiago Y. Oliveira & Gaëlle Breton & Katrina G. Millard & Martina Turroja & Allison Butler & Victor Ramos & Michael S. Seaman & Jacqueline D. Ree, 2022. "Prolonged viral suppression with anti-HIV-1 antibody therapy," Nature, Nature, vol. 606(7913), pages 368-374, June.
  • Handle: RePEc:nat:nature:v:606:y:2022:i:7913:d:10.1038_s41586-022-04597-1
    DOI: 10.1038/s41586-022-04597-1
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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. Daniel B. Reeves & Christian Gaebler & Thiago Y. Oliveira & Michael J. Peluso & Joshua T. Schiffer & Lillian B. Cohn & Steven G. Deeks & Michel C. Nussenzweig, 2023. "Impact of misclassified defective proviruses on HIV reservoir measurements," Nature Communications, Nature, vol. 14(1), pages 1-10, 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.

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