Effectiveness and safety of integrase strand transfer inhibitors in Spain: a prospective real-world study

Introduction: Second-generation integrase strand transfer inhibitors (INSTIs) are preferred treatment options worldwide, and dolutegravir (DTG) is the treatment of choice in resource-limited settings. Nevertheless, in some resource-limited settings, these drugs are not always available. An analysis...

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Autores: Ramon Santos, Jose, Casadellà, Maria, Noguera Julian, Marc, Micán Rivera, Rafael, Domingo Pedrol, Pere, Antela, Antonio, Portilla, Joaquin, Sanz Sanz, Jesús, Montero Alonso, Marta, Navarro Mercade, Jordi, Masiá, Mar, Valcarce Pardeiro, Nieves, Pérez Álvarez, Nuria|||0000-0001-6582-1553
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universitat Politècnica de Catalunya (UPC)
Repositorio:UPCommons. Portal del coneixement obert de la UPC
Idioma:inglés
OAI Identifier:oai:upcommons.upc.edu:2117/400635
Acceso en línea:https://hdl.handle.net/2117/400635
https://dx.doi.org/10.3389/fcimb.2023.1187999
Access Level:acceso abierto
Palabra clave:Biomathematics
Biomatemàtica
Classificació AMS::92 Biology and other natural sciences::92B Mathematical biology in general
Àrees temàtiques de la UPC::Matemàtiques i estadística::Matemàtica aplicada a les ciències
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spelling Effectiveness and safety of integrase strand transfer inhibitors in Spain: a prospective real-world studyRamon Santos, JoseCasadellà, MariaNoguera Julian, MarcMicán Rivera, RafaelDomingo Pedrol, PereAntela, AntonioPortilla, JoaquinSanz Sanz, JesúsMontero Alonso, MartaNavarro Mercade, JordiMasiá, MarValcarce Pardeiro, NievesPérez Álvarez, Nuria|||0000-0001-6582-1553BiomathematicsBiomatemàticaClassificació AMS::92 Biology and other natural sciences::92B Mathematical biology in generalÀrees temàtiques de la UPC::Matemàtiques i estadística::Matemàtica aplicada a les ciènciesIntroduction: Second-generation integrase strand transfer inhibitors (INSTIs) are preferred treatment options worldwide, and dolutegravir (DTG) is the treatment of choice in resource-limited settings. Nevertheless, in some resource-limited settings, these drugs are not always available. An analysis of the experience with the use of INSTIs in unselected adults living with HIV may be of help to make therapeutic decisions when second-generation INSTIs are not available. This study aimed to evaluate the real-life effectiveness and safety of dolutegravir (DTG), elvitegravir/cobicistat (EVG/c), and raltegravir (RAL) in a large Spanish cohort of HIV-1-infected patients. Methods: Real-world study of adults living with HIV who initiated integrase INSTIs DTG, EVG/c, and RAL-based regimens in three settings (ART-naïve patients, ART-switching, and ART-salvage patients). The primary endpoint was the median time to treatment discontinuation after INSTI-based regimen initiation. Proportion of patients experiencing virological failure (VF) (defined as two consecutive viral loads (VL) =200 copies/mL at 24 weeks or as a single determination of VL =1,000 copies/mL while receiving DTG, EVG/c or RAL, and at least 3 months after INSTI initiation) and time to VF were also evaluated. Results: Virological effectiveness of EVG/c- and RAL-based regimens was similar to that of DTG when given as first-line and salvage therapy. Treatment switching for reasons other than virological failure was more frequent in subjects receiving EVG/c and, in particular, RAL. Naïve patients with CD4+ nadir <100 cells/µL were more likely to develop VF, particularly if they initiated RAL or EVG/c. In the ART switching population, initiation of RAL and EVG/c was associated with both VF and INSTI discontinuation. There were no differences in the time to VF and INSTI discontinuation between DTG, EVG/c and RAL. Immunological parameters improved in the three groups and for the three drugs assessed. Safety and tolerability were consistent with expected safety profiles. Discussion: Whereas second-generation INSTIs are preferred treatment options worldwide, and DTG is one of the treatment of choices in resource-limited settings, first-generation INSTIs may still provide high virological and immunological effectiveness when DTG is not available.Peer Reviewed20232023-06-2620242024-01-31journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/2117/400635https://dx.doi.org/10.3389/fcimb.2023.1187999reponame:UPCommons. Portal del coneixement obert de la UPCinstname:Universitat Politècnica de Catalunya (UPC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:upcommons.upc.edu:2117/4006352026-05-27T15:37:01Z
dc.title.none.fl_str_mv Effectiveness and safety of integrase strand transfer inhibitors in Spain: a prospective real-world study
title Effectiveness and safety of integrase strand transfer inhibitors in Spain: a prospective real-world study
spellingShingle Effectiveness and safety of integrase strand transfer inhibitors in Spain: a prospective real-world study
Ramon Santos, Jose
Biomathematics
Biomatemàtica
Classificació AMS::92 Biology and other natural sciences::92B Mathematical biology in general
Àrees temàtiques de la UPC::Matemàtiques i estadística::Matemàtica aplicada a les ciències
title_short Effectiveness and safety of integrase strand transfer inhibitors in Spain: a prospective real-world study
title_full Effectiveness and safety of integrase strand transfer inhibitors in Spain: a prospective real-world study
title_fullStr Effectiveness and safety of integrase strand transfer inhibitors in Spain: a prospective real-world study
title_full_unstemmed Effectiveness and safety of integrase strand transfer inhibitors in Spain: a prospective real-world study
title_sort Effectiveness and safety of integrase strand transfer inhibitors in Spain: a prospective real-world study
dc.creator.none.fl_str_mv Ramon Santos, Jose
Casadellà, Maria
Noguera Julian, Marc
Micán Rivera, Rafael
Domingo Pedrol, Pere
Antela, Antonio
Portilla, Joaquin
Sanz Sanz, Jesús
Montero Alonso, Marta
Navarro Mercade, Jordi
Masiá, Mar
Valcarce Pardeiro, Nieves
Pérez Álvarez, Nuria|||0000-0001-6582-1553
author Ramon Santos, Jose
author_facet Ramon Santos, Jose
Casadellà, Maria
Noguera Julian, Marc
Micán Rivera, Rafael
Domingo Pedrol, Pere
Antela, Antonio
Portilla, Joaquin
Sanz Sanz, Jesús
Montero Alonso, Marta
Navarro Mercade, Jordi
Masiá, Mar
Valcarce Pardeiro, Nieves
Pérez Álvarez, Nuria|||0000-0001-6582-1553
author_role author
author2 Casadellà, Maria
Noguera Julian, Marc
Micán Rivera, Rafael
Domingo Pedrol, Pere
Antela, Antonio
Portilla, Joaquin
Sanz Sanz, Jesús
Montero Alonso, Marta
Navarro Mercade, Jordi
Masiá, Mar
Valcarce Pardeiro, Nieves
Pérez Álvarez, Nuria|||0000-0001-6582-1553
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Biomathematics
Biomatemàtica
Classificació AMS::92 Biology and other natural sciences::92B Mathematical biology in general
Àrees temàtiques de la UPC::Matemàtiques i estadística::Matemàtica aplicada a les ciències
topic Biomathematics
Biomatemàtica
Classificació AMS::92 Biology and other natural sciences::92B Mathematical biology in general
Àrees temàtiques de la UPC::Matemàtiques i estadística::Matemàtica aplicada a les ciències
description Introduction: Second-generation integrase strand transfer inhibitors (INSTIs) are preferred treatment options worldwide, and dolutegravir (DTG) is the treatment of choice in resource-limited settings. Nevertheless, in some resource-limited settings, these drugs are not always available. An analysis of the experience with the use of INSTIs in unselected adults living with HIV may be of help to make therapeutic decisions when second-generation INSTIs are not available. This study aimed to evaluate the real-life effectiveness and safety of dolutegravir (DTG), elvitegravir/cobicistat (EVG/c), and raltegravir (RAL) in a large Spanish cohort of HIV-1-infected patients. Methods: Real-world study of adults living with HIV who initiated integrase INSTIs DTG, EVG/c, and RAL-based regimens in three settings (ART-naïve patients, ART-switching, and ART-salvage patients). The primary endpoint was the median time to treatment discontinuation after INSTI-based regimen initiation. Proportion of patients experiencing virological failure (VF) (defined as two consecutive viral loads (VL) =200 copies/mL at 24 weeks or as a single determination of VL =1,000 copies/mL while receiving DTG, EVG/c or RAL, and at least 3 months after INSTI initiation) and time to VF were also evaluated. Results: Virological effectiveness of EVG/c- and RAL-based regimens was similar to that of DTG when given as first-line and salvage therapy. Treatment switching for reasons other than virological failure was more frequent in subjects receiving EVG/c and, in particular, RAL. Naïve patients with CD4+ nadir <100 cells/µL were more likely to develop VF, particularly if they initiated RAL or EVG/c. In the ART switching population, initiation of RAL and EVG/c was associated with both VF and INSTI discontinuation. There were no differences in the time to VF and INSTI discontinuation between DTG, EVG/c and RAL. Immunological parameters improved in the three groups and for the three drugs assessed. Safety and tolerability were consistent with expected safety profiles. Discussion: Whereas second-generation INSTIs are preferred treatment options worldwide, and DTG is one of the treatment of choices in resource-limited settings, first-generation INSTIs may still provide high virological and immunological effectiveness when DTG is not available.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-06-26
2024
2024-01-31
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/2117/400635
https://dx.doi.org/10.3389/fcimb.2023.1187999
url https://hdl.handle.net/2117/400635
https://dx.doi.org/10.3389/fcimb.2023.1187999
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
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dc.source.none.fl_str_mv reponame:UPCommons. Portal del coneixement obert de la UPC
instname:Universitat Politècnica de Catalunya (UPC)
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