Fimepinostat, a novel dual inhibitor of HDAC and PI3K, effectively reverses HIV-1 latency ex vivo without T cell activation
Jesper D Gunst, Kathrine Kjaer, Rikke Olesen, Thomas A Rasmussen, Lars Ostergaard, Paul W Denton, Ole S Sogaard, Martin Tolstrup
JOURNAL OF VIRUS ERADICATION | MEDISCRIPT LTD | Published : 2019
Objectives: To test the potential of fimepinostat (CUDC-907), a dual inhibitor of histone deacetylases (HDAC) and phosphatidylinositol-3-kinases (PI3K), to reverse human immunodeficiency virus type 1 (HIV-1) latency in infected cell lines and in CD4+ T cells from HIV-1-infected donors on long-term combination antiretroviral therapy (cART). Methods: Latently HIV-1-infected J-lat Tat-GFP and ACH-2 cell lines were stimulated with clinically relevant concentrations of fimepinostat using the HDAC inhibitors (HDACi) panobinostat and romidepsin for comparison. Next, CD4+ T cells from donors living with HIV-1 on long-term cART were stimulated ex vivo and cell-associated unspliced HIV-1 RNA was measu..View full abstract
The participants living with HIV-1 were recruited from the Nordic HIV Latency and Cure Research Collaboration cohort, which has been supported by an educational grant to JDG via the Gilead Nordic Fellowship Programme 2015 and the Scandinavian Society for Antimicrobial Chemotherapy Foundation.