Bar-On, Yotam, Gruell, Henning, Schoofs, Till, Pai, Joy A., Nogueira, Lilian, Butler, Allison L., Millard, Katrina, Lehmann, Clara, Suarez, Isabelle, Oliveira, Thiago Y., Karagounis, Theodora ORCID: 0000-0003-1481-9589, Cohen, Yehuda Z., Wyen, Christoph, Scholten, Stefan, Handl, Lisa, Belblidia, Shiraz, Dizon, Juan P., Vehreschild, Joerg J., Witmer-Pack, Maggi, Shimeliovich, Irina, Jain, Kanika, Fiddike, Kerstin, Seaton, Kelly E., Yates, Nicole L., Horowitz, Jill, Gulick, Roy M., Pfeifer, Nico, Tomaras, Georgia D., Seaman, Michael S., Faetkenheuer, Gerd, Caskey, Marina, Klein, Florian and Nussenzweig, Michel C. (2018). Safety and antiviral activity of combination HIV-1 broadly neutralizing antibodies in viremic individuals. Nat. Med., 24 (11). S. 1701 - 1710. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1546-170X

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Abstract

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 variants(1,2). Combinations of drugs can establish long-term control, however, antiretroviral therapy (ART) requires daily dosing, can cause side effects and does not eradicate the infection(3,4). Although anti-HIV-1 antibodies constitute a potential alternative to ART(5,6), treatment of viremic individuals with a single antibody also results in emergence of resistant viral variants(7-9). Moreover, combinations of first-generation anti-HIV-1 broadly neutralizing antibodies (bNAbs) had little measurable effect on the infection(10-12). Here we report on a phase 1b clinical trial (NCT02825797) in which two potent bNAbs, 3BNC117(13) and 10-1074(14), 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 log(10) 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Bar-On, YotamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gruell, HenningUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schoofs, TillUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pai, Joy A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nogueira, LilianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Butler, Allison L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Millard, KatrinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lehmann, ClaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Suarez, IsabelleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oliveira, Thiago Y.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Karagounis, TheodoraUNSPECIFIEDorcid.org/0000-0003-1481-9589UNSPECIFIED
Cohen, Yehuda Z.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wyen, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scholten, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Handl, LisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Belblidia, ShirazUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dizon, Juan P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vehreschild, Joerg J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Witmer-Pack, MaggiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shimeliovich, IrinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jain, KanikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fiddike, KerstinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seaton, Kelly E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yates, Nicole L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Horowitz, JillUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gulick, Roy M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pfeifer, NicoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tomaras, Georgia D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seaman, Michael S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Faetkenheuer, GerdUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Caskey, MarinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klein, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nussenzweig, Michel C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-167252
DOI: 10.1038/s41591-018-0186-4
Journal or Publication Title: Nat. Med.
Volume: 24
Number: 11
Page Range: S. 1701 - 1710
Date: 2018
Publisher: NATURE PUBLISHING GROUP
Place of Publication: NEW YORK
ISSN: 1546-170X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CD4(+) T-CELLS; MONOCLONAL-ANTIBODY; ANTI-HIV-1 ANTIBODIES; PASSIVE IMMUNOTHERAPY; ANTIRETROVIRAL DRUGS; SUPPRESSES VIREMIA; IMMUNE-RESPONSES; DURABLE CONTROL; HUMANIZED MICE; THERAPYMultiple languages
Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & ExperimentalMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/16725

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