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; p. 418
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 20.03.2020
• Subjects: AIDS Vaccines - immunology; Apoptosis - drug effects; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; Depsipeptides - pharmacology; Depsipeptides - therapeutic use; Follow-Up Studies; Histone Code; Histone Deacetylase Inhibitors - pharmacology; Histone Deacetylase Inhibitors - therapeutic use; HIV Infections - drug therapy; HIV Infections - immunology; HIV-1; Humans; Immunization, Secondary; Immunogenicity, Vaccine; Immunologic Memory; Immunology; Lymphocyte Activation - drug effects; Programmed Cell Death 1 Receptor - biosynthesis; Programmed Cell Death 1 Receptor - genetics; Proof of Concept Study; RNA, Viral - genetics; Virus Latency - drug effects; Virus Replication; therapeutic vaccine; HDAC inhibitor; kick&kill strategy; latency reversing agent (LRA); romidepsin
• ISSN: 1664-3224; 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. and 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, 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 observations are replicated , 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.