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Nat Med. 2018 Nov;24(11):1701-1707. doi: 10.1038/s41591-018-0186-4. Epub 2018 Sep 26.

Safety and antiviral activity of combination HIV-1 broadly neutralizing antibodies in viremic individuals.

Author information

1
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
2
Laboratory of Experimental Immunology, Institute of Virology, University Hospital Cologne, Cologne, Germany.
3
Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany.
4
German Center for Infection Research, Partner Site Bonn-Cologne, Cologne, Germany.
5
Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
6
Praxis am Ebertplatz, Cologne, Germany.
7
Praxis Hohenstaufenring, Cologne, Germany.
8
Methods in Medical Informatics, Department of Computer Science, University of Tübingen, Tübingen, Germany.
9
Duke Human Vaccine Institute, Duke University, Durham, NC, USA.
10
Division of Infectious Diseases, Weill Cornell Medicine, New York, NY, USA.
11
Medical Faculty, University of Tübingen, Tübingen, Germany.
12
German Center for Infection Research, Partner Site Tübingen, Tübingen, Germany.
13
Max Planck Institute for Informatics, Saarbrücken, Germany.
14
Departments of Surgery, Immunology and Molecular Genetics and Microbiology, Duke University, Durham, NC, USA.
15
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
16
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA. mcaskey@rockefeller.edu.
17
Laboratory of Experimental Immunology, Institute of Virology, University Hospital Cologne, Cologne, Germany. florian.klein@uk-koeln.de.
18
German Center for Infection Research, Partner Site Bonn-Cologne, Cologne, Germany. florian.klein@uk-koeln.de.
19
Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany. florian.klein@uk-koeln.de.
20
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA. nussen@rockefeller.edu.
21
Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA. nussen@rockefeller.edu.

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 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.

PMID:
30258217
PMCID:
PMC6221973
[Available on 2019-03-26]
DOI:
10.1038/s41591-018-0186-4

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