HIV-1-specific T-cell responses and exhaustion profiles in people with HIV after switching to dual therapy vs. maintaining triple therapy based on integrase inhibitors

© 2023 The Authors. Published by Elsevier Masson SAS. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Detalles Bibliográficos
Autores: Muñoz-Muela, Esperanza, Trujillo-Rodríguez, María, Serna, Ana, Saborido-Alconchel, Abraham, Ruiz-Mateos, Ezequiel, López-Cortés, Luis F., Gutiérrez Valencia, Alicia
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/350761
Acceso en línea:http://hdl.handle.net/10261/350761
Access Level:acceso abierto
Palabra clave:HIV treatment
Treatment simplification
Dual therapy
Triple therapy
HIV-specific T-cell response
T-cell exhaustion
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spelling HIV-1-specific T-cell responses and exhaustion profiles in people with HIV after switching to dual therapy vs. maintaining triple therapy based on integrase inhibitorsMuñoz-Muela, EsperanzaTrujillo-Rodríguez, MaríaSerna, AnaSaborido-Alconchel, AbrahamRuiz-Mateos, EzequielLópez-Cortés, Luis F.Gutiérrez Valencia, AliciaHIV treatmentTreatment simplificationDual therapyTriple therapyHIV-specific T-cell responseT-cell exhaustion© 2023 The Authors. Published by Elsevier Masson SAS. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).[Background] Dual therapy (DT) has shown comparable results to triple therapy (TT) in efficacy and other immunological aspects. However, there are still some concerns about DT, including several immunological features. Therefore, we evaluated whether HIV-1-specific memory T-cell responses and exhaustion phenotypes are adversely influenced after simplification to DT.[Methods] HIV-1-specific CD4+ and CD8+ T-cell responses were assessed by intracellular cytokine and degranulation marker staining, and polyfunctionality indexes after stimulation with a Gag peptide pool. Exhaustion phenotypes were evaluated by PD-1, TIM-3, and LAG-3 expression in CD4+ and CD8+ T cells.[Results] Forty participants in the TRIDUAL trial (ClinicalTrials.gov: NCT03447873) who were randomized to continue integrase inhibitor-based TT (n = 20) or to switch to DT (dolutegravir or darunavir/cobicistat plus lamivudine) (n = 20). After 96 weeks, the magnitude of CD4+ and CD8+ T-cell responses was similar in both treatment arms (p = 0.221 and p = 0.602, respectively). The CD4+ polyfunctionality index decreased in the TT arm (p = 0.013) and remained stable in the DT arm, while the polyfunctionality of CD8+ T cells was unchanged in both arms. There was a significant decrease in the expression of PD-1, TIM-3, and the co-expression of PD-1+TIM-3+LAG-3+, and PD-1 +TIM-3 + in both CD4+ and CD8+ T cells. However, the decrease in the expression of exhaustion markers did not improve HIV-1-specific T-cell responses.[Conclusions] Our results suggest that simplification to DT does not negatively influence the HIV-1-specific T-cell response or the exhaustion phenotype after 96 weeks of follow-up.This work was supported by Instituto de Salud Carlos III through the project (PI18/01298) to LFLC; Subprogram Miguel Servet (CP19/00159) to AGV, PFIS contracts (FI19/00304) to EMM, and to ASA (FI21/00165) from the Ministerio de Ciencia e Innovación, Spain; co-financed by the European Regional Development Fund "a way to make Europe".Peer reviewedElsevierInstituto de Salud Carlos IIIMinisterio de Ciencia e Innovación (España)European CommissionConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202420242023info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/350761reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/PI18%2F01298The underlying dataset has been published as supplementary material of the article in the publisher platform at https://doi.org/10.1016/j.biopha.2023.115750https://doi.org/10.1016/j.biopha.2023.115750Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3507612026-05-22T06:33:51Z
dc.title.none.fl_str_mv HIV-1-specific T-cell responses and exhaustion profiles in people with HIV after switching to dual therapy vs. maintaining triple therapy based on integrase inhibitors
title HIV-1-specific T-cell responses and exhaustion profiles in people with HIV after switching to dual therapy vs. maintaining triple therapy based on integrase inhibitors
spellingShingle HIV-1-specific T-cell responses and exhaustion profiles in people with HIV after switching to dual therapy vs. maintaining triple therapy based on integrase inhibitors
Muñoz-Muela, Esperanza
HIV treatment
Treatment simplification
Dual therapy
Triple therapy
HIV-specific T-cell response
T-cell exhaustion
title_short HIV-1-specific T-cell responses and exhaustion profiles in people with HIV after switching to dual therapy vs. maintaining triple therapy based on integrase inhibitors
title_full HIV-1-specific T-cell responses and exhaustion profiles in people with HIV after switching to dual therapy vs. maintaining triple therapy based on integrase inhibitors
title_fullStr HIV-1-specific T-cell responses and exhaustion profiles in people with HIV after switching to dual therapy vs. maintaining triple therapy based on integrase inhibitors
title_full_unstemmed HIV-1-specific T-cell responses and exhaustion profiles in people with HIV after switching to dual therapy vs. maintaining triple therapy based on integrase inhibitors
title_sort HIV-1-specific T-cell responses and exhaustion profiles in people with HIV after switching to dual therapy vs. maintaining triple therapy based on integrase inhibitors
dc.creator.none.fl_str_mv Muñoz-Muela, Esperanza
Trujillo-Rodríguez, María
Serna, Ana
Saborido-Alconchel, Abraham
Ruiz-Mateos, Ezequiel
López-Cortés, Luis F.
Gutiérrez Valencia, Alicia
author Muñoz-Muela, Esperanza
author_facet Muñoz-Muela, Esperanza
Trujillo-Rodríguez, María
Serna, Ana
Saborido-Alconchel, Abraham
Ruiz-Mateos, Ezequiel
López-Cortés, Luis F.
Gutiérrez Valencia, Alicia
author_role author
author2 Trujillo-Rodríguez, María
Serna, Ana
Saborido-Alconchel, Abraham
Ruiz-Mateos, Ezequiel
López-Cortés, Luis F.
Gutiérrez Valencia, Alicia
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
Ministerio de Ciencia e Innovación (España)
European Commission
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv HIV treatment
Treatment simplification
Dual therapy
Triple therapy
HIV-specific T-cell response
T-cell exhaustion
topic HIV treatment
Treatment simplification
Dual therapy
Triple therapy
HIV-specific T-cell response
T-cell exhaustion
description © 2023 The Authors. Published by Elsevier Masson SAS. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
publishDate 2023
dc.date.none.fl_str_mv 2023
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/350761
url http://hdl.handle.net/10261/350761
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/PI18%2F01298
The underlying dataset has been published as supplementary material of the article in the publisher platform at https://doi.org/10.1016/j.biopha.2023.115750
https://doi.org/10.1016/j.biopha.2023.115750
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
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