Panobinostat, a histone deacetylase inhibitor, for latent-virus reactivation in HIV-infected patients on suppressive antiretroviral therapy: a phase 1/2, single group, clinical trial

Thomas Aagaard Rasmussen, Martin Tolstrup, Christel Brinkmann, Rikke Olesen, Christian Erikstrup, Ajantha Solomon, Anni Winkelmann, Sarah E Palmer, Charles A Dinarello, Maria Jose Buzon, Mathias Lichterfeld, Sharon Ruth Lewin, Lars Jorgen Ostergaard, Ole Schmeltz Sogaard

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Abstract

Background: Activating the expression of latent virus is an approach that might form part of an HIV cure. We assessed the ability of the histone deacetylase inhibitor panobinostat to disrupt HIV-1 latency and the safety of this strategy. Methods: In this phase 1/2 clinical trial, we included aviraemic adults with HIV treated at Aarhus University Hospital, Denmark. Participants received oral panobinostat (20 mg) three times per week every other week for 8 weeks while maintaining combination antiretroviral therapy. The primary outcome was change from baseline of cell-associated unspliced HIV RNA. Secondary endpoints were safety, plasma HIV RNA, total and integrated HIV DNA, infectious units per million CD4 T cells, and time to viral rebound during an optional analytical treatment interruption of antiretroviral therapy. This trial is registered with ClinicalTrial.gov, number NCT01680094. Findings: We enrolled 15 patients. The level of cell-associated unspliced HIV RNA increased signifi cantly at all timepoints when patients were taking panobinostat (p
Original languageEnglish
Pages (from-to)e13 - e21
Number of pages9
JournalThe Lancet HIV
Volume1
Issue number1
DOIs
Publication statusPublished - 2014

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