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Cure and Long-Term Remission Strategies.

Luisa Mori1, Susana T Valente2

  • 1Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, USA.

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|January 5, 2022
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Summary

Researchers are exploring a "block-and-lock" strategy to achieve a functional cure for HIV. This approach aims to epigenetically silence the virus, preventing its reactivation and spread without ongoing antiretroviral therapy (ART).

Keywords:
Block-and-lockEpigenetic silencingHIV functional cureHIV transcriptionTat inhibitors

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Area of Science:

  • Virology
  • Immunology
  • Molecular Biology
  • Drug Discovery

Background:

  • Antiretroviral therapy (ART) suppresses HIV but viral rebound occurs upon interruption.
  • HIV persists in latent reservoirs, causing chronic immune activation, inflammation, and comorbidities.
  • Current ART controls viremia but does not eliminate the latent viral reservoir.

Purpose of the Study:

  • To review the principles of the 'block-and-lock' approach for a functional HIV cure.
  • To discuss strategies for achieving long-term, durable control of HIV expression.
  • To explore methods for silencing proviral DNA and preventing viral reactivation.

Main Methods:

  • Review of existing scientific literature on HIV latency and functional cure strategies.
  • Discussion of epigenetic silencing mechanisms targeting HIV transcription.
  • Analysis of small molecule inhibitors targeting HIV transcription for proof-of-concept.

Main Results:

  • The 'block-and-lock' strategy proposes epigenetic silencing to induce a profound latent state.
  • Proof-of-concept demonstrated using a small molecule targeting HIV transcription.
  • This approach aims for durable viral control without continuous antiretroviral therapy.

Conclusions:

  • The 'block-and-lock' approach offers a promising strategy for a functional HIV cure.
  • Epigenetic silencing can potentially lock HIV into a non-replicative state.
  • Further research into silencing strategies is crucial for developing effective HIV cure interventions.