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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, 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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