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Title: Epigenetic landscape in the kick-and-kill therapeutic vaccine BCN02 clinical trial is associated with antiretroviral treatment interruption (ATI) outcome
Author: Oriol Tordera, Bruna
Esteve Codina, Anna
Berdasco, María
Rosás Umbert, Míriam
Gonçalves, Elena
Duran Castells, Clara
Català Moll, Francesc
Llano, Anuska
Cedeño, Samandhy
Puertas, Maria C.
Tolstrup, Martin
Søgaard, Ole S.
Clotet, Bonaventura, 1953-
Martínez Picado, Javier
Hanke, Tomáš
Combadiere, Behazine
Paredes, Roger
Hartigan-O'connor, Dennis
Esteller, Manel
Meulbroek, Michael
Calle, María Luz
Sanchez Pla, Alex
Moltó, José
Mothe, Beatriz
Brander, Christian
Ruiz Riol, Marta
Keywords: VIH (Virus)
HIV (Viruses)
Issue Date: 1-Apr-2022
Publisher: Elsevier
Abstract: Background The BCN02-trial combined therapeutic vaccination with a viral latency reversing agent (romidepsin, RMD) in HIV-1-infected individuals and included a monitored antiretroviral pause (MAP) as an efficacy read-out identifying individuals with an early or late (< or > 4weeks) viral-rebound. Integrated-omics analyses were applied prior treatment interruption to identify markers of virus control during MAP.& nbsp;Methods PBMC, whole-genome DNA methylation and transcriptomics were assessed in 14 BCN02 participants, including 8 Early and 4 Late viral-rebound individuals. Chromatin state, histone marks and integration analysis (his tone-3 acetylation (H3Ac), viral load, proviral levels and HIV-specific T cells responses) were included. REDUC-trial samples (n = 5) were included as a control group for RMD administration alone.& nbsp;Findings DNA methylation imprints after receiving the complete intervention discriminated Early versus Late viral rebound individuals before MAP. Also, differential chromatin accessibility and histone marks at DNA methylation level were detected. Importantly, the differential DNA methylation positions (DMPs) between Early and Late rebounders before MAP were strongly associated with viral load, proviral levels as well as the HIV-specific T-cell responses. Most of these DMPs were already present prior to the intervention and accentuated after RMD infusion.& nbsp;Interpretation This study identifies host DNA methylation profiles and epigenetic cascades that are predictive of subsequent virus control in a kick-and-kill HIV cure strategy. Copyright (C)& nbsp;2022 The Authors. Published by Elsevier B.V.& nbsp;
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It is part of: eBioMedicine, 2022, vol. 78
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ISSN: 2352-3964
Appears in Collections:Articles publicats en revistes (Ciències Clíniques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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