Combination therapy with anti-HIV-1 antibodies maintains viral suppression

Nature. 2018 Sep;561(7724):479-484. doi: 10.1038/s41586-018-0531-2. Epub 2018 Sep 26.

Abstract

Individuals infected with HIV-1 require lifelong antiretroviral therapy, because interruption of treatment leads to rapid rebound viraemia. Here we report on a phase 1b clinical trial in which a combination of 3BNC117 and 10-1074, two potent monoclonal anti-HIV-1 broadly neutralizing antibodies that target independent sites on the HIV-1 envelope spike, was administered during analytical treatment interruption. Participants received three infusions of 30 mg kg-1 of each antibody at 0, 3 and 6 weeks. Infusions of the two antibodies were generally well-tolerated. The nine enrolled individuals with antibody-sensitive latent viral reservoirs maintained suppression for between 15 and more than 30 weeks (median of 21 weeks), and none developed viruses that were resistant to both antibodies. We conclude that the combination of the anti-HIV-1 monoclonal antibodies 3BNC117 and 10-1074 can maintain long-term suppression in the absence of antiretroviral therapy in individuals with antibody-sensitive viral reservoirs.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / immunology
  • Anti-HIV Agents / therapeutic use
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neutralizing / administration & dosage
  • Antibodies, Neutralizing / adverse effects
  • Antibodies, Neutralizing / immunology
  • Antibodies, Neutralizing / therapeutic use*
  • Binding Sites, Antibody
  • Broadly Neutralizing Antibodies
  • Carrier State / drug therapy
  • Carrier State / immunology
  • Carrier State / virology
  • Drug Combinations
  • Drug Resistance, Viral
  • Female
  • HIV Antibodies / administration & dosage
  • HIV Antibodies / adverse effects
  • HIV Antibodies / immunology
  • HIV Antibodies / therapeutic use*
  • HIV Envelope Protein gp160 / immunology
  • HIV Infections / drug therapy*
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / immunology*
  • HIV-1 / isolation & purification
  • Historically Controlled Study
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Phylogeny
  • Viremia / drug therapy
  • Viremia / immunology
  • Viremia / prevention & control
  • Viremia / virology
  • Virus Activation / immunology
  • Virus Latency / immunology*
  • Young Adult

Substances

  • 3BNC117 antibody
  • Anti-HIV Agents
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neutralizing
  • Broadly Neutralizing Antibodies
  • Drug Combinations
  • HIV Antibodies
  • HIV Envelope Protein gp160
  • gp160 protein, Human immunodeficiency virus 1