Cell
Volume 158, Issue 5, 28 August 2014, Pages 989-999
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Article
Broadly Neutralizing Antibodies and Viral Inducers Decrease Rebound from HIV-1 Latent Reservoirs in Humanized Mice

https://doi.org/10.1016/j.cell.2014.07.043Get rights and content
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Highlights

  • bNAbs can be used for postexposure prophylaxis (PEP) in humanized mice

  • bNAb PEP efficacy requires Fc-receptor binding

  • bNAbs plus a single inducer of HIV-1 transcription do not reduce viral rebound

  • bNAbs plus a combination of inducers significantly reduce viral rebound

Summary

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.

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