Scheid, Johannes F., Horwitz, Joshua A., Bar-On, Yotam, Kreider, Edward F., Lu, Ching-Lan, Lorenzi, Julio C. C., Feldmann, Anna, Braunschweig, Malte, Nogueira, Lilian, Oliveira, Thiago ORCID: 0000-0002-2654-0879, Shimeliovich, Irina, Patel, Roshni, Burke, Leah, Cohen, Yehuda Z., Hadrigan, Sonya, Settler, Allison, Witmer-Pack, Maggi, West, Anthony P., Jr., Juelg, Boris ORCID: 0000-0002-4687-9626, Keler, Tibor, Hawthorne, Thomas, Zingman, Barry, Gulick, Roy M., Pfeifer, Nico ORCID: 0000-0002-4647-8566, Learn, Gerald H., Seaman, Michael S., Bjorkman, Pamela J., Klein, Florian, Schlesinger, Sarah J., Walker, Bruce D., Hahn, Beatrice H., Nussenzweig, Michel C. and Caskey, Marina ORCID: 0000-0003-1727-8693 (2016). HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption. Nature, 535 (7613). S. 556 - 573. LONDON: NATURE PUBLISHING GROUP. ISSN 1476-4687

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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(1), 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 mu g 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Scheid, Johannes F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Horwitz, Joshua A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bar-On, YotamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kreider, Edward F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lu, Ching-LanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lorenzi, Julio C. C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Feldmann, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Braunschweig, MalteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nogueira, LilianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oliveira, ThiagoUNSPECIFIEDorcid.org/0000-0002-2654-0879UNSPECIFIED
Shimeliovich, IrinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Patel, RoshniUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Burke, LeahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cohen, Yehuda Z.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hadrigan, SonyaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Settler, AllisonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Witmer-Pack, MaggiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
West, Anthony P., Jr.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Juelg, BorisUNSPECIFIEDorcid.org/0000-0002-4687-9626UNSPECIFIED
Keler, TiborUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hawthorne, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zingman, BarryUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gulick, Roy M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pfeifer, NicoUNSPECIFIEDorcid.org/0000-0002-4647-8566UNSPECIFIED
Learn, Gerald H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seaman, Michael S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bjorkman, Pamela J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klein, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schlesinger, Sarah J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Walker, Bruce D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hahn, Beatrice H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nussenzweig, Michel C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Caskey, MarinaUNSPECIFIEDorcid.org/0000-0003-1727-8693UNSPECIFIED
URN: urn:nbn:de:hbz:38-269473
DOI: 10.1038/nature18929
Journal or Publication Title: Nature
Volume: 535
Number: 7613
Page Range: S. 556 - 573
Date: 2016
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 1476-4687
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
BROADLY NEUTRALIZING ANTIBODIES; ANTIRETROVIRAL THERAPY; MONOCLONAL-ANTIBODIES; GENETIC-DETERMINANTS; PASSIVE TRANSFER; POTENT; SEQUENCE; REPLICATION; RESPONSES; IMMUNOTHERAPYMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/26947

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