Journal article
Comparison of HDAC inhibitors in clinical development: Effect on HIV production in latently infected cells and T-cell activation
TA Rasmussen, OS Søgaard, C Brinkmann, F Wightman, SR Lewin, J Melchjorsen, C Dinarello, L Østergaard, M Tolstrup
Human Vaccines and Immunotherapeutics | TAYLOR & FRANCIS INC | Published : 2013
DOI: 10.4161/hv.23800
Abstract
Objective: We aimed to compare the potential for inducing HIV production and the effect on T-cell activation of potent HDAC inhibitors undergoing clinical investigation. Design: In vitro study. Results: The various HDAC inhibitors displayed significant potency differences in stimulating HIV-1 expression from the latently infected cell lines with panobinostat > givinostat ≈ belinostat > vorinostat > valproic acid. Panobinostat was significantly more potent than all other HDAC inhibitors and induced virus production even in the very low concentration range 8-31 nM. The proportion of primary T-cells expressing the early activation marker CD69 increased moderately in all HDAC inhibitor-treated c..
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Awarded by National Institute of Allergy and Infectious Diseases
Funding Acknowledgements
The Aids Foundation, Denmark; The Institute of Clinical Medicine, Aarhus University; and The Hede Nielsen Foundation, Denmark, funded the study. Italfarmaco S.p.A. delivered ITF2357 (givinostat) free of charge for use in this study. S. L. has received institutional research grants from Merck, Gilead and Janssen and has received institutional payment for lectures/educational services from Gilead, Viiv and Merck. L.O. has received consultancy and speaker's fee from: Abbott, MSD, Pfizer, Bristol-Meyer Squibb, GlaxoSmithKline, ViiV Healthcare, Gilead and Tibotec. For the remaining authors, no conflicts of interest were declared.