Safety and Effect of The HDAC Inhibitor Panobinostat on HIV-1 Expression in Patients on Suppressive HAART

Summary

The purpose of this study is to assess the safety and ability of panobinostat to re-activate HIV transcription in latently infected CD4+ T-cells among HIV-infected patients on stable antiretroviral therapy

Timeline

Start

2012-09

Primary completion

2013-09

Completion

2014-01

Outcome

Met primary endpoint

paper The level of cell-associated unspliced HIV RNA increased significantly at all timepoints when patients were taking panobinostat (p < 0·0001). PMID 26423811 ↗

Publications

• Corley MJ, Pang APS, Rasmussen TA, Tolstrup M, Sogaard OS, Ndhlovu LC. Candidate host epigenetic marks predictive for HIV reservoir size, responsiveness to latency reversal, and viral rebound. AIDS. 2021 Nov 15;35(14):2269-2279. doi: 10.1097/QAD.0000000000003065.
• Garrido C, Tolstrup M, Sogaard OS, Rasmussen TA, Allard B, Soriano-Sarabia N, Archin NM, Margolis DM. In-vivo administration of histone deacetylase inhibitors does not impair natural killer cell function in HIV+ individuals. AIDS. 2019 Mar 15;33(4):605-613. doi: 10.1097/QAD.0000000000002112.
• Bjerg Christensen A, Dige A, Vad-Nielsen J, Brinkmann CR, Bendix M, Ostergaard L, Tolstrup M, Sogaard OS, Rasmussen TA, Randel Nyengaard J, Agnholt J, Denton PW. Administration of Panobinostat Is Associated with Increased IL-17A mRNA in the Intestinal Epithelium of HIV-1 Patients. Mediators Inflamm. 2015;2015:120605. doi: 10.1155/2015/120605. Epub 2015 Dec 1.
• Rasmussen TA, Tolstrup M, Brinkmann CR, Olesen R, Erikstrup C, Solomon A, Winckelmann A, Palmer S, Dinarello C, Buzon M, Lichterfeld M, Lewin SR, Ostergaard L, Sogaard OS. 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. Lancet HIV. 2014 Oct;1(1):e13-21. doi: 10.1016/S2352-3018(14)70014-1. Epub 2014 Sep 15.

Drugs

Indications