AUTHOR=Rosás-Umbert Miriam , Ruiz-Riol Marta , Fernández Marco A. , Marszalek Marta , Coll Pep , Manzardo Christian , Cedeño Samandhy , Miró José M. , Clotet Bonaventura , Hanke Tomáš , Moltó José , Mothe Beatriz , Brander Christian , the BCN02 study group , Benet Susana , Brander Christian , Cedeño Samandhy , Clotet Bonaventura , Coll Pep , Llano Anuksa , Martinez-Picado Javier , Marszalek Marta , Morón-López Sara , Mothe Beatriz , Paredes Roger , Puertas Maria C. , Rosás-Umbert Miriam , Ruiz-Riol Marta , Escrig Roser , Gel Silvia , López Miriam , Miranda Cristina , Moltó José , Muñoz Jose , Perez-Alvarez Nuria , Puig Jordi , Revollo Boris , Toro Jessica , Barriocanal Ana Maria , Farré Magi , Perez-Reche Cristina , Valle Marta , Manzardo Christian , Ambrosioni Juan , Ruiz Irene , Rovira Cristina , Ligero Carmen , Miro Jose M. , Carrillo Antonio , Meulbroek Michael , Pujol Ferran , Saz Jorge , Borthwick Nicola , Crook Alison , Wee Edmund G. , Hanke Tomáš TITLE=In vivo Effects of Romidepsin on T-Cell Activation, Apoptosis and Function in the BCN02 HIV-1 Kick&Kill Clinical Trial JOURNAL=Frontiers in Immunology VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.00418 DOI=10.3389/fimmu.2020.00418 ISSN=1664-3224 ABSTRACT=

Romidepsin (RMD) is a well-characterized histone deacetylase inhibitor approved for the treatment of cutaneous T-cell lymphoma. in vitro and in vivo studies have demonstrated that it is able to induce HIV-1 gene expression in latently infected CD4+ T cells from HIV-1+ individuals on suppressive antiretroviral therapy. However, in vitro experiments suggested that RMD could also impair T-cell functionality, particularly of activated T cells. Thus, the usefulness of RMD in HIV-1 kick&kill strategies, that aim to enhance the immune system elimination of infected cells after inducing HIV-1 viral reactivation, may be limited. In order to address whether the in vitro observations are replicated in vivo, we determined the effects of RMD on the total and HIV-1-specific T-cell populations in longitudinal samples from the BCN02 kick&kill clinical trial (NCT02616874). BCN02 was a proof-of-concept study in 15 early treated HIV-1+ individuals that combined MVA.HIVconsv vaccination with three weekly infusions of RMD given as a latency reversing agent. Our results show that RMD induced a transient increase in the frequency of apoptotic T cells and an enhanced activation of vaccine-induced T cells. Although RMD reduced the number of vaccine-elicited T cells secreting multiple cytokines, viral suppressive capacity of CD8+ T cells was preserved over the RMD treatment. These observations have important implications for the design of effective kick&kill strategies for the HIV-1 cure.