PLoS Pathogens (Sep 2015)

The Depsipeptide Romidepsin Reverses HIV-1 Latency In Vivo.

  • Ole S Søgaard,
  • Mette E Graversen,
  • Steffen Leth,
  • Rikke Olesen,
  • Christel R Brinkmann,
  • Sara K Nissen,
  • Anne Sofie Kjaer,
  • Mariane H Schleimann,
  • Paul W Denton,
  • William J Hey-Cunningham,
  • Kersten K Koelsch,
  • Giuseppe Pantaleo,
  • Kim Krogsgaard,
  • Maja Sommerfelt,
  • Remi Fromentin,
  • Nicolas Chomont,
  • Thomas A Rasmussen,
  • Lars Østergaard,
  • Martin Tolstrup

DOI
https://doi.org/10.1371/journal.ppat.1005142
Journal volume & issue
Vol. 11, no. 9
p. e1005142

Abstract

Read online

UnlabelledPharmacologically-induced activation of replication competent proviruses from latency in the presence of antiretroviral treatment (ART) has been proposed as a step towards curing HIV-1 infection. However, until now, approaches to reverse HIV-1 latency in humans have yielded mixed results. Here, we report a proof-of-concept phase Ib/IIa trial where 6 aviremic HIV-1 infected adults received intravenous 5 mg/m2 romidepsin (Celgene) once weekly for 3 weeks while maintaining ART. Lymphocyte histone H3 acetylation, a cellular measure of the pharmacodynamic response to romidepsin, increased rapidly (maximum fold range: 3.7–7.7 relative to baseline) within the first hours following each romidepsin administration. Concurrently, HIV-1 transcription quantified as copies of cell-associated un-spliced HIV-1 RNA increased significantly from baseline during treatment (range of fold-increase: 2.4–5.0; p = 0.03). Plasma HIV-1 RNA increased from Trial registrationclinicaltrials.gov NTC02092116.