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Combination therapy with anti-HIV-1 antibodies maintains viral suppression.
Mendoza, Pilar; Gruell, Henning; Nogueira, Lilian; Pai, Joy A; Butler, Allison L; Millard, Katrina; Lehmann, Clara; Suárez, Isabelle; Oliveira, Thiago Y; Lorenzi, Julio C C; Cohen, Yehuda Z; Wyen, Christoph; Kümmerle, Tim; Karagounis, Theodora; Lu, Ching-Lan; Handl, Lisa; Unson-O'Brien, Cecilia; Patel, Roshni; Ruping, Carola; Schlotz, Maike; Witmer-Pack, Maggi; Shimeliovich, Irina; Kremer, Gisela; Thomas, Eleonore; Seaton, Kelly E; Horowitz, Jill; West, Anthony P; Bjorkman, Pamela J; Tomaras, Georgia D; Gulick, Roy M; Pfeifer, Nico; Fätkenheuer, Gerd; Seaman, Michael S; Klein, Florian; Caskey, Marina; Nussenzweig, Michel C.
Afiliação
  • Mendoza P; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
  • Gruell H; Laboratory of Experimental Immunology, Institute of Virology, University Hospital Cologne, Cologne, Germany.
  • Nogueira L; Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany.
  • Pai JA; German Center for Infection Research, partner site Bonn-Cologne, Cologne, Germany.
  • Butler AL; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
  • Millard K; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
  • Lehmann C; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
  • Suárez I; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
  • Oliveira TY; Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany.
  • Lorenzi JCC; German Center for Infection Research, partner site Bonn-Cologne, Cologne, Germany.
  • Cohen YZ; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
  • Wyen C; Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany.
  • Kümmerle T; German Center for Infection Research, partner site Bonn-Cologne, Cologne, Germany.
  • Karagounis T; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
  • Lu CL; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
  • Handl L; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
  • Unson-O'Brien C; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
  • Patel R; Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany.
  • Ruping C; Praxis am Ebertplatz, Cologne, Germany.
  • Schlotz M; Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany.
  • Witmer-Pack M; Praxis am Ebertplatz, Cologne, Germany.
  • Shimeliovich I; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
  • Kremer G; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
  • Thomas E; Methods in Medical Informatics, Department of Computer Science, University of Tübingen, Tübingen, Germany.
  • Seaton KE; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
  • Horowitz J; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
  • West AP; Laboratory of Experimental Immunology, Institute of Virology, University Hospital Cologne, Cologne, Germany.
  • Bjorkman PJ; Laboratory of Experimental Immunology, Institute of Virology, University Hospital Cologne, Cologne, Germany.
  • Tomaras GD; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
  • Gulick RM; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
  • Pfeifer N; Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany.
  • Fätkenheuer G; Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany.
  • Seaman MS; Duke Human Vaccine Institute, Duke University, Durham, NC, USA.
  • Klein F; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
  • Caskey M; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
  • Nussenzweig MC; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Nature ; 561(7724): 479-484, 2018 09.
Article em En | MEDLINE | ID: mdl-30258136
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Anticorpos Anti-HIV / Infecções por HIV / HIV-1 / Latência Viral / Anticorpos Neutralizantes / Anticorpos Monoclonais Tipo de estudo: Clinical_trials Idioma: En Revista: Nature Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Anticorpos Anti-HIV / Infecções por HIV / HIV-1 / Latência Viral / Anticorpos Neutralizantes / Anticorpos Monoclonais Tipo de estudo: Clinical_trials Idioma: En Revista: Nature Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos