HIV-1 suppression and durable control by combining single broadly neutralizing antibodies and antiretroviral drugs in humanized mice

Proc Natl Acad Sci U S A. 2013 Oct 8;110(41):16538-43. doi: 10.1073/pnas.1315295110. Epub 2013 Sep 16.


Effective control of HIV-1 infection in humans is achieved using combinations of antiretroviral therapy (ART) drugs. In humanized mice (hu-mice), control of viremia can be achieved using either ART or by immunotherapy using combinations of broadly neutralizing antibodies (bNAbs). Here we show that treatment of HIV-1-infected hu-mice with a combination of three highly potent bNAbs not only resulted in complete viremic control but also led to a reduction in cell-associated HIV-1 DNA. Moreover, lowering the initial viral load by coadministration of ART and immunotherapy enabled prolonged viremic control by a single bNAb after ART was withdrawn. Similarly, a single injection of adeno-associated virus directing expression of one bNAb produced durable viremic control after ART was terminated. We conclude that immunotherapy reduces plasma viral load and cell-associated HIV-1 DNA and that decreasing the initial viral load enables single bNAbs to control viremia in hu-mice.

Keywords: CD4bs; glycan; gp160.

Publication types

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

MeSH terms

  • Animals
  • Anti-Retroviral Agents / immunology*
  • Anti-Retroviral Agents / pharmacology
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Neutralizing / pharmacology
  • DNA Primers / genetics
  • DNA, Viral / metabolism
  • Dependovirus
  • Drug Therapy, Combination
  • HIV Infections / prevention & control*
  • HIV-1 / drug effects*
  • HIV-1 / immunology*
  • Humans
  • Immunotherapy / methods*
  • Mice
  • Mice, Transgenic
  • Real-Time Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Viral Load / drug effects


  • Anti-Retroviral Agents
  • Antibodies, Neutralizing
  • DNA Primers
  • DNA, Viral