Broadly neutralizing antibodies and viral inducers decrease rebound from HIV-1 latent reservoirs in humanized mice

Cell. 2014 Aug 28;158(5):989-999. doi: 10.1016/j.cell.2014.07.043. Epub 2014 Aug 14.


Latent reservoirs of HIV-1-infected cells are refractory to antiretroviral therapies (ART) and remain the major barrier to curing HIV-1. Because latently infected cells are long-lived, immunologically invisible, and may undergo homeostatic proliferation, a "shock and kill" approach has been proposed to eradicate this reservoir by combining ART with inducers of viral transcription. However, all attempts to alter the HIV-1 reservoir in vivo have failed to date. Using humanized mice, we show that broadly neutralizing antibodies (bNAbs) can interfere with establishment of a silent reservoir by Fc-FcR-mediated mechanisms. In established infection, bNAbs or bNAbs plus single inducers are ineffective in preventing viral rebound. However, bNAbs plus a combination of inducers that act by independent mechanisms synergize to decrease the reservoir as measured by viral rebound. Thus, combinations of inducers and bNAbs constitute a therapeutic strategy that impacts the establishment and maintenance of the HIV-1 reservoir in humanized mice.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-HIV Agents / therapeutic use
  • Antibodies, Neutralizing / administration & dosage*
  • Antibodies, Neutralizing / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CTLA-4 Antigen / administration & dosage
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • HIV-1 / physiology
  • Heterocyclic Compounds, 4 or More Rings / administration & dosage
  • Humans
  • Hydroxamic Acids / administration & dosage
  • Immunoglobulin Fc Fragments / immunology
  • Mice
  • Receptors, Fc / immunology
  • Transcription, Genetic / drug effects*
  • Virus Latency / drug effects*
  • Vorinostat


  • Anti-HIV Agents
  • Antibodies, Neutralizing
  • CTLA-4 Antigen
  • GSK1210151A
  • Heterocyclic Compounds, 4 or More Rings
  • Hydroxamic Acids
  • Immunoglobulin Fc Fragments
  • Receptors, Fc
  • Vorinostat