Søgaard OS Graversen ME Leth S Olesen R Brinkmann CR Nissen SK Kjaer AS Schleimann MH Denton PW Hey-Cunningham WJ Koelsch KK Pantaleo G Krogsgaard K Sommerfelt M Fromentin R Chomont N Rasmussen TA Østergaard L Tolstrup M 2015 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 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 <20 copies/mL at baseline to readily quantifiable levels at multiple post-infusion time-points in 5 of 6 patients (range 46–103 copies/mL following the second infusion, p = 0.04). Importantly, romidepsin did not decrease the number of HIV-specific T cells or inhibit T cell cytokine production. Adverse events (all grade 1–2) were consistent with the known side effects of romidepsin. In conclusion, romidepsin safely induced HIV-1 transcription resulting in plasma HIV-1 RNA that was readily detected with standard commercial assays demonstrating that significant reversal of HIV-1 latency in vivo is possible without blunting T cell-mediated immune responses. These finding have major implications for future trials aiming to eradicate the HIV-1 reservoir. TRIAL REGISTRATION clinicaltrials.gov NTC02092116. application/pdf https://sonar.ch/global/documents/265225 eng info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.ppat.1005142 info:eu-repo/semantics/altIdentifier/pmid/26379282 info:eu-repo/semantics/openAccess PLoS pathogens. - 2015 AIDS Vaccines Acetylation Adult Anti-HIV Agents Antiretroviral Therapy, Highly Active Biomarkers Cohort Studies Depsipeptides Drug Interactions Female Follow-Up Studies HIV Infections HIV-1 Histones Humans Infusions, Intravenous Lymphocytes Male Middle Aged Protein Processing, Post-Translational RNA, Viral Viral Load Virus Activation Virus Latency The Depsipeptide Romidepsin Reverses HIV-1 Latency In Vivo. http://purl.org/coar/resource_type/c_6501