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Title: | Preserved central nervous system functioning after use of romidepsin as a latency-reversing agent in an HIV cure strategy |
Author: | Muñoz Moreno, Jose Antonio Carrillo Molina, Sara Martínez Zalacaín, Ignacio Miranda, Cristina Manzardo, Christian Coll, Pep Meulbroek, Michael Hanke, Thomas Garolera, Maite Miró, Josep M. Brander, Christian Clotet Sala, Bonaventura Soriano-Mas, Carles Molto, Jose Mothe, Beatriz BCN02-Neuro Substudy Group |
Others: | Fundació Lluita Contra la SIDA i les Malalties Infeccioses (FLS) Hospital Universitari Germans Trias i Pujol Universitat Oberta de Catalunya. Estudis de Psicologia i Ciències de l'Educació Institut d'Investigació Biomèdica de Bellvitge Universitat de Barcelona (UB) Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Projecte dels NOMS-Hispanosida Institut de Recerca de la Sida (IrsiCaixa) University of Oxford Kumamoto Daigaku Consorci Sanitari de Terrassa Universitat de Vic-Universitat Central de Catalunya (UVic-UCC) Institució Catalana de Recerca i Estudis Avançats (ICREA) Instituto de Salud Carlos III Universitat Autònoma de Barcelona (UAB) |
Citation: | Muñoz-Moreno, J.A., Carrillo-Molina, S., Martínez-Zalacaín, I., Miranda, C., Manzardo, C., Coll, P., Meulbroek, M., Hanke, T., Garolera, M., Miró, J.M., Brander, C., Clotet, B., Soriano-Mas, C., Moltó, J. & Mothe, B. (2022). Preserved central nervous system functioning after use of romidepsin as a latency-reversing agent in an HIV cure strategy. AIDS, 36(3), 363-372. doi: 10.1097/QAD.0000000000003121 |
Abstract: | Objective: To assess the central nervous system (CNS) impact of a kick&kill HIV cure strategy using therapeutic vaccine MVA.HIVconsv and the histone deacetylase inhibitor (HDACi) romidepsin (RMD) as latency-reversing agent. Design: Neurological observational substudy of the BCN02 trial (NCT02616874), a proof-of-concept, open-label, single-arm, phase I clinical trial testing the safety and immunogenicity of the MVA.HIVconsv vaccine and RMD in early-treated HIV-1-infected individuals. A monitored antiretroviral pause (MAP) was performed, with cART resumption after 2 pVL more than 2000 copies/ml. Reinitiated participants were followed for 24 weeks. Methods: Substudy participation was offered to all BCN02 participants (N = 15). Evaluations covered cognitive, functional, and brain imaging outcomes, performed before RMD administration (pre-RMD), after three RMD infusions (post-RMD), and at the end of the study (EoS). A group of early-treated HIV-1-infected individuals with matched clinical characteristics was additionally recruited (n = 10). Primary endpoint was change in a global cognitive score (NPZ-6). Results: Eleven participants from BCN02 trial were enrolled. No significant changes were observed in cognitive, functional, or brain imaging outcomes from pre-RMD to post-RMD. No relevant alterations were detected from pre-RMD to EoS either. Scores at EoS were similar in participants off cART for 32 weeks (n = 3) and those who resumed therapy for 24 weeks (n = 7). Controls showed comparable punctuations in NPZ-6 across all timepoints. Conclusion: No detrimental effects on cognitive status, functional outcomes, or brain imaging parameters were observed after using the HDACi RMD as latency-reversing agent with the MVA.HIVconsv vaccine in early-treated HIV-1-infected individuals. CNS safety was also confirmed after completion of the MAP. |
Keywords: | central nervous system histone deacetylase inhibitors HIV infection kick&kill strategies MVA.HIVconsv romidepsin |
DOI: | http://doi.org/10.1097/QAD.0000000000003121 |
Document type: | info:eu-repo/semantics/article |
Version: | info:eu-repo/semantics/acceptedVersion |
Issue Date: | 1-Mar-2022 |
Publication license: | https://creativecommons.org/licenses/by-nd/4.0 NO |
Appears in Collections: | Articles Articles cientÍfics |
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muñoz_aids_preserved.pdf | 343,72 kB | Adobe PDF | View/Open |
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