• Marina Caskey, Florian Klein, Julio C C Lorenzi, Michael S Seaman, Anthony P West, Noreen Buckley, Gisela Kremer, Lilian Nogueira, Malte Braunschweig, Johannes F Scheid, Joshua A Horwitz, Irina Shimeliovich, Sivan Ben-Avraham, Maggi Witmer-Pack, Martin Platten, Clara Lehmann, Leah A Burke, Thomas Hawthorne, Robert J Gorelick, Bruce D Walker, Tibor Keler, Roy M Gulick, Gerd Fätkenheuer, Sarah J Schlesinger, and Michel C Nussenzweig.
• Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.
• Nature. 2015 Jun 25; 522 (7557): 487-91.

AbstractHIV-1 immunotherapy with a combination of first generation monoclonal antibodies was largely ineffective in pre-clinical and clinical settings and was therefore abandoned. However, recently developed single-cell-based antibody cloning methods have uncovered a new generation of far more potent broadly neutralizing antibodies to HIV-1 (refs 4, 5). These antibodies can prevent infection and suppress viraemia in humanized mice and nonhuman primates, but their potential for human HIV-1 immunotherapy has not been evaluated. Here we report the results of a first-in-man dose escalation phase 1 clinical trial of 3BNC117, a potent human CD4 binding site antibody, in uninfected and HIV-1-infected individuals. 3BNC117 infusion was well tolerated and demonstrated favourable pharmacokinetics. A single 30 mg kg(-1) infusion of 3BNC117 reduced the viral load in HIV-1-infected individuals by 0.8-2.5 log10 and viraemia remained significantly reduced for 28 days. Emergence of resistant viral strains was variable, with some individuals remaining sensitive to 3BNC117 for a period of 28 days. We conclude that, as a single agent, 3BNC117 is safe and effective in reducing HIV-1 viraemia, and that immunotherapy should be explored as a new modality for HIV-1 prevention, therapy and cure.

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