Journal article

The Depsipeptide Romidepsin Reverses HIV-1 Latency In Vivo

Ole S Sogaard, 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 Ostergaard, Martin Tolstrup

PLoS Pathogens | PUBLIC LIBRARY SCIENCE | Published : 2015

Abstract

UNLABELLED: Pharmacologically-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 ..

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