title: HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption.
abstract: Interruption 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.
authors.forename: Johannes F
authors.initials: JF
authors.lastname: Scheid
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Horwitz
authors.forename: Yotam
authors.initials: Y
authors.lastname: Bar-On
authors.forename: Edward F
authors.initials: EF
authors.lastname: Kreider
authors.forename: Ching-Lan
authors.initials: CL
authors.lastname: Lu
authors.forename: Julio C C
authors.initials: JC
authors.lastname: Lorenzi
authors.forename: Anna
authors.initials: A
authors.lastname: Feldmann
authors.forename: Malte
authors.initials: M
authors.lastname: Braunschweig
authors.forename: Lilian
authors.initials: L
authors.lastname: Nogueira
authors.forename: Thiago
authors.initials: T
authors.lastname: Oliveira
authors.forename: Irina
authors.initials: I
authors.lastname: Shimeliovich
authors.forename: Roshni
authors.initials: R
authors.lastname: Patel
authors.forename: Leah
authors.initials: L
authors.lastname: Burke
authors.forename: Yehuda Z
authors.initials: YZ
authors.lastname: Cohen
authors.forename: Sonya
authors.initials: S
authors.lastname: Hadrigan
authors.forename: Allison
authors.initials: A
authors.lastname: Settler
authors.forename: Maggi
authors.initials: M
authors.lastname: Witmer-Pack
authors.forename: Anthony P
authors.initials: AP
authors.lastname: West
authors.forename: Boris
authors.initials: B
authors.lastname: Juelg
authors.forename: Tibor
authors.initials: T
authors.lastname: Keler
authors.forename: Thomas
authors.initials: T
authors.lastname: Hawthorne
authors.forename: Barry
authors.initials: B
authors.lastname: Zingman
authors.forename: Roy M
authors.initials: RM
authors.lastname: Gulick
authors.forename: Nico
authors.initials: N
authors.lastname: Pfeifer
authors.forename: Gerald H
authors.initials: GH
authors.lastname: Learn
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Bjorkman
authors.forename: Florian
authors.initials: F
authors.lastname: Klein
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Schlesinger
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Beatrice H
authors.initials: BH
authors.lastname: Hahn
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
authors.forename: Marina
authors.initials: M
authors.lastname: Caskey
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D001665:Binding Sites / Q000187:drug effects / Q000276:immunology; D000080908:Broadly Neutralizing Antibodies; D015704:CD4 Antigens / Q000378:metabolism; D004197:Disease Reservoirs / Q000821:virology; D004334:Drug Administration Schedule; D005260:Female; D015483:HIV Antibodies / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D019302:HIV Envelope Protein gp160 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development* / Q000276:immunology*; D065386:Historically Controlled Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D011533:Proviruses / Q000187:drug effects / Q000254:growth & development / Q000276:immunology; D013997:Time Factors; D014018:Tissue Distribution; D019562:Viral Load / Q000187:drug effects / Q000276:immunology; D055815:Young Adult
chemical_list: C000599675:3BNC117 antibody; D019380:Anti-HIV Agents; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing; D000080908:Broadly Neutralizing Antibodies; D015704:CD4 Antigens; D015483:HIV Antibodies; D019302:HIV Envelope Protein gp160