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Combination antibody therapy results in long-term viral suppression in HIV infection

Combination antibody therapy results in long-term viral suppression in HIV infection

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, Christoph Wyen, Tim Kümmerle, Theodora Karagounis, Ching-Lan Lu, Lisa Handl, Cecilia Unson-O’Brien, Roshni Patel, Carola Ruping, Maike Schlotz, Maggi Witmer-Pack, Irina Shimeliovich, Gisela Kremer, Eleonore Thomas, Kelly E. Seaton, Jill Horowitz, Anthony P. West Jr., Pamela J. Bjorkman, Georgia D. Tomaras, Roy M. Gulick, Nico Pfeifer, Gerd Fätkenheuer, Michael S. Seaman, Florian Klein#§, Marina Caskey#§, Michel C. Nussenzweig#§ (# shared Authors; § corresponding authors)

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. Nature, 9/26/2018

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

Yotam Bar-On# Henning Gruell#, Till Schoofs, Joy A. Pai, Lilian Nogueira, Allison L. Butler, Katrina Millard, Clara Lehmann, Isabelle Suárez, Thiago Y. Oliveira, Theodora Karagounis, Yehuda Z. Cohen, Christoph Wyen, Stefan Scholten, Lisa Handl, Shiraz Belblidia, Juan P. Dizon, Jörg J. Vehreschild, Maggi Witmer-Pack, Irina Shimeliovich, Kanika Jain, Kerstin Fiddike, Kelly E. Seaton, Nicole L. Yates, Jill Horowitz, Roy M. Gulick, Nico Pfeifer, Georgia D. Tomaras, Michael S. Seaman, Gerd Fätkenheuer, Marina Caskey#§, Florian Klein#§, Michel C. Nussenzweig#§ (# shared authors; § corresponding authors)

Monotherapy of HIV-1 infection with single antiretroviral agents is ineffective because error-prone HIV-1 replication leads to the production of drug-resistant viral variants1,2. Combinations of drugs can establish long-term control, however, antiretroviral therapy (ART) requires daily dosing, can cause side effects and does not eradicate the infection3,4. Although anti-HIV-1 antibodies constitute a potential alternative to ART5,6, treatment of viremic individuals with a single antibody also results in emergence of resistant viral variants7-9. Moreover, combinations of first-generation anti-HIV-1 broadly neutralizing antibodies (bNAbs) had little measurable effect on the infection10-12. Here we report on a phase 1b clinical trial ( NCT02825797 ) in which two potent bNAbs, 3BNC11713 and 10-107414, were administered in combination to seven HIV-1 viremic individuals. Infusions of 30 mg kg-1 of each of the antibodies were well-tolerated. In the four individuals with dual antibody-sensitive viruses, immunotherapy resulted in an average reduction in HIV-1 viral load of 2.05 log10 copies per ml that remained significantly reduced for three months following the first of up to three infusions. In addition, none of these individuals developed resistance to both antibodies. Larger studies will be necessary to confirm the efficacy of antibody combinations in reducing HIV-1 viremia and limiting the emergence of resistant viral variants. Nature, 9/26/2018

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