Preserved central nervous system functioning after use of romidepsin as a latency-reversing agent in an HIV cure strategy.
Journal
AIDS (London, England)
ISSN: 1473-5571
Titre abrégé: AIDS
Pays: England
ID NLM: 8710219
Informations de publication
Date de publication:
01 03 2022
01 03 2022
Historique:
pubmed:
10
11
2021
medline:
9
4
2022
entrez:
9
11
2021
Statut:
ppublish
Résumé
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. 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. 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). 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. 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.
Identifiants
pubmed: 34750296
doi: 10.1097/QAD.0000000000003121
pii: 00002030-202203010-00005
doi:
Substances chimiques
Anti-Retroviral Agents
0
Depsipeptides
0
Histone Deacetylase Inhibitors
0
romidepsin
CX3T89XQBK
Banques de données
ClinicalTrials.gov
['NCT02616874']
Types de publication
Clinical Trial
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
363-372Subventions
Organisme : Medical Research Council
ID : G0701669
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1001757
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N023668/1
Pays : United Kingdom
Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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