• Johannes F Scheid, Joshua A Horwitz, Yotam Bar-On, Edward F Kreider, Ching-Lan Lu, Julio C C Lorenzi, Anna Feldmann, Malte Braunschweig, Lilian Nogueira, Thiago Oliveira, Irina Shimeliovich, Roshni Patel, Leah Burke, Yehuda Z Cohen, Sonya Hadrigan, Allison Settler, Maggi Witmer-Pack, Anthony P West, Boris Juelg, Tibor Keler, Thomas Hawthorne, Barry Zingman, Roy M Gulick, Nico Pfeifer, Gerald H Learn, Michael S Seaman, Pamela J Bjorkman, Florian Klein, Sarah J Schlesinger, Bruce D Walker, Beatrice H Hahn, and Michel C Nussenzweig.
• Nature. 2016 Jul 28; 535 (7613): 556-60.

AbstractInterruption of combination antiretroviral therapy in HIV-1-infected individuals leads to rapid viral rebound. Here we report the results of a phase IIa open label clinical trial evaluating 3BNC117,a broad and potent neutralizing antibody against the CD4 binding site of the HIV-1 Env protein, during analytical treatment interruption in 13 HIV-1-infected individuals. Participants with 3BNC117-sensitive virus outgrowth cultures were enrolled. Results show that two or four 30 mg kg(-1) 3BNC117 infusions,separated by 3 or 2 weeks, respectively, are generally well tolerated.Infusions are associated with a delay in viral rebound of 5-9 weeks after two infusions, and up to 19 weeks after four infusions, or an average of 6.7 and 9.9 weeks, respectively, compared with 2.6 weeks for historical controls (P < 0.00001). Rebound viruses arise predominantly from a single provirus. In most individuals,emerging viruses show increased resistance, indicating escape.However, 30% of participants remained suppressed until antibody concentrations waned below 20 μg ml(-1), and the viruses emerging in all but one of these individuals showed no apparent resistance to 3BCN117, suggesting failure to escape over a period of 9-19 weeks.We conclude that the administration of 3BNC117 exerts strong selective pressure on HIV-1 emerging from latent reservoirs during analytical treatment interruption in humans.

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