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

Publication ,  Journal Article
Bar-On, Y; Gruell, H; Schoofs, T; Pai, JA; Nogueira, L; Butler, AL; Millard, K; Lehmann, C; Suárez, I; Oliveira, TY; Karagounis, T; Cohen, YZ ...
Published in: Nat Med
November 2018

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.

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Published In

Nat Med

DOI

EISSN

1546-170X

Publication Date

November 2018

Volume

24

Issue

11

Start / End Page

1701 / 1707

Location

United States

Related Subject Headings

  • Young Adult
  • Viremia
  • Viral Load
  • Middle Aged
  • Male
  • Immunotherapy
  • Immunology
  • Humans
  • HIV-1
  • HIV Seropositivity
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Bar-On, Y., Gruell, H., Schoofs, T., Pai, J. A., Nogueira, L., Butler, A. L., … Nussenzweig, M. C. (2018). Safety and antiviral activity of combination HIV-1 broadly neutralizing antibodies in viremic individuals. Nat Med, 24(11), 1701–1707. https://doi.org/10.1038/s41591-018-0186-4
Bar-On, Yotam, Henning Gruell, Till Schoofs, Joy A. Pai, Lilian Nogueira, Allison L. Butler, Katrina Millard, et al. “Safety and antiviral activity of combination HIV-1 broadly neutralizing antibodies in viremic individuals.Nat Med 24, no. 11 (November 2018): 1701–7. https://doi.org/10.1038/s41591-018-0186-4.
Bar-On Y, Gruell H, Schoofs T, Pai JA, Nogueira L, Butler AL, et al. Safety and antiviral activity of combination HIV-1 broadly neutralizing antibodies in viremic individuals. Nat Med. 2018 Nov;24(11):1701–7.
Bar-On, Yotam, et al. “Safety and antiviral activity of combination HIV-1 broadly neutralizing antibodies in viremic individuals.Nat Med, vol. 24, no. 11, Nov. 2018, pp. 1701–07. Pubmed, doi:10.1038/s41591-018-0186-4.
Bar-On Y, Gruell H, Schoofs T, Pai JA, Nogueira L, Butler AL, Millard K, Lehmann C, Suárez I, Oliveira TY, Karagounis T, Cohen YZ, Wyen C, Scholten S, Handl L, Belblidia S, Dizon JP, Vehreschild JJ, Witmer-Pack M, Shimeliovich I, Jain K, Fiddike K, Seaton KE, Yates NL, Horowitz J, Gulick RM, Pfeifer N, Tomaras GD, Seaman MS, Fätkenheuer G, Caskey M, Klein F, Nussenzweig MC. Safety and antiviral activity of combination HIV-1 broadly neutralizing antibodies in viremic individuals. Nat Med. 2018 Nov;24(11):1701–1707.

Published In

Nat Med

DOI

EISSN

1546-170X

Publication Date

November 2018

Volume

24

Issue

11

Start / End Page

1701 / 1707

Location

United States

Related Subject Headings

  • Young Adult
  • Viremia
  • Viral Load
  • Middle Aged
  • Male
  • Immunotherapy
  • Immunology
  • Humans
  • HIV-1
  • HIV Seropositivity