In vivo Effects of Romidepsin on T-Cell Activation, Apoptosis and Function in the BCN02 HIV-1 Kick Kill Clinical Trial

• Published in: Frontiers in immunology Vol. 11
• Main Authors: Miriam Rosás-Umbert, Marta Ruiz-Riol, Marco A. Fernández, Marta Marszalek, Pep Coll, Christian Manzardo, Samandhy Cedeño, José M. Miró, Bonaventura Clotet, Tomáš Hanke, José Moltó, Beatriz Mothe, Christian Brander, the BCN02 study group, Susana Benet, Anuksa Llano, Javier Martinez-Picado, Sara Morón-López, Roger Paredes, Maria C. Puertas, Roser Escrig, Silvia Gel, Miriam López, Cristina Miranda, Jose Muñoz, Nuria Perez-Alvarez, Jordi Puig, Boris Revollo, Jessica Toro, Ana Maria Barriocanal, Magi Farré, Cristina Perez-Reche, Marta Valle, Juan Ambrosioni, Irene Ruiz, Cristina Rovira, Carmen Ligero, Jose M. Miro, Antonio Carrillo, Michael Meulbroek, Ferran Pujol, Jorge Saz, Nicola Borthwick, Alison Crook, Edmund G. Wee
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 01.03.2020
• Subjects: HDAC inhibitor; kick&kill strategy; latency reversing agent (LRA); romidepsin; therapeutic vaccine
• ISSN: 1664-3224
• DOI: 10.3389/fimmu.2020.00418

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.