Frontiers in Immunology (Mar 2020)

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

  • Miriam Rosás-Umbert,
  • Miriam Rosás-Umbert,
  • Marta Ruiz-Riol,
  • Marco A. Fernández,
  • Marta Marszalek,
  • Pep Coll,
  • Christian Manzardo,
  • Samandhy Cedeño,
  • José M. Miró,
  • Bonaventura Clotet,
  • Bonaventura Clotet,
  • Bonaventura Clotet,
  • Bonaventura Clotet,
  • Tomáš Hanke,
  • Tomáš Hanke,
  • José Moltó,
  • José Moltó,
  • Beatriz Mothe,
  • Beatriz Mothe,
  • Beatriz Mothe,
  • Christian Brander,
  • Christian Brander,
  • Christian Brander,
  • the BCN02 study group,
  • Susana Benet,
  • Christian Brander,
  • Samandhy Cedeño,
  • Bonaventura Clotet,
  • Pep Coll,
  • Anuksa Llano,
  • Javier Martinez-Picado,
  • Marta Marszalek,
  • Sara Morón-López,
  • Beatriz Mothe,
  • Roger Paredes,
  • Maria C. Puertas,
  • Miriam Rosás-Umbert,
  • Marta Ruiz-Riol,
  • Roser Escrig,
  • Silvia Gel,
  • Miriam López,
  • Cristina Miranda,
  • José Moltó,
  • Jose Muñoz,
  • Nuria Perez-Alvarez,
  • Jordi Puig,
  • Boris Revollo,
  • Jessica Toro,
  • Ana Maria Barriocanal,
  • Magi Farré,
  • Cristina Perez-Reche,
  • Marta Valle,
  • Christian Manzardo,
  • 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,
  • Tomáš Hanke

DOI
https://doi.org/10.3389/fimmu.2020.00418
Journal volume & issue
Vol. 11

Abstract

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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.

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