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Related Experiment Video

Updated: Apr 3, 2026

High Throughput In Vitro Assessment of Latency Reversing Agents on HIV Transcription and Splicing
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The Depsipeptide Romidepsin Reverses HIV-1 Latency In Vivo.

Ole S Søgaard1, Mette E Graversen2, Steffen Leth2

  • 1Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.

Plos Pathogens
|September 18, 2015
PubMed
Summary

Romidepsin effectively reversed HIV-1 latency in adults on antiretroviral treatment, increasing viral transcription and detectable plasma HIV-1 RNA without impairing T cell immunity. This demonstrates a viable strategy for HIV-1 reservoir eradication.

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Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors
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Area of Science:

  • Immunology
  • Virology
  • Pharmacology

Background:

  • Reversing HIV-1 latency is crucial for eradicating the viral reservoir.
  • Previous attempts to reverse latency in humans have shown inconsistent results.
  • Antiretroviral treatment (ART) alone does not eliminate the latent HIV-1 reservoir.

Purpose of the Study:

  • To evaluate the safety and efficacy of romidepsin in reversing HIV-1 latency in aviremic adults on ART.
  • To assess the pharmacodynamic effects of romidepsin on HIV-1 transcription and T cell responses.
  • To determine if romidepsin can induce detectable levels of HIV-1 RNA in plasma.

Main Methods:

  • A phase Ib/IIa proof-of-concept trial involving 6 aviremic HIV-1 infected adults.
  • Patients received intravenous romidepsin (5 mg/m2) weekly for 3 weeks while continuing ART.
  • Measurements included lymphocyte histone H3 acetylation, cell-associated un-spliced HIV-1 RNA, plasma HIV-1 RNA, and HIV-specific T cell responses.

Main Results:

  • Romidepsin rapidly increased lymphocyte histone H3 acetylation, indicating pharmacodynamic engagement.
  • Significant increases in cell-associated un-spliced HIV-1 RNA were observed during treatment (p = 0.03).
  • Plasma HIV-1 RNA became detectable in 5 of 6 patients post-infusion (p = 0.04).
  • Romidepsin did not reduce HIV-specific T cell counts or cytokine production.
  • Adverse events were mild (grade 1–2) and consistent with known romidepsin side effects.

Conclusions:

  • Romidepsin safely and effectively induced HIV-1 transcription in vivo, leading to detectable plasma HIV-1 RNA.
  • This study demonstrates the feasibility of reversing HIV-1 latency without compromising T cell-mediated immunity.
  • These findings support romidepsin as a potential therapeutic agent in future HIV-1 eradication strategies.