A Randomized Trial of Dolutegravir Plus Darunavir/Cobicistat as a Switch Strategy in HIV-1-Infected Patients With Resistance to at Least 2 Antiretroviral Classes.

BACKGROUND: Suppressed patients with drug-resistant HIV-1 require effective and simple antiretroviral therapy to maintain treatment adherence and viral suppression. METHODS: This randomized, open-label, noninferiority, multicenter pilot study involved HIV-infected adults who met the following criter...

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Autores: Santos JR, Domingo P, Portilla J, Gutiérrez F, Imaz A, Vilchez H, Curran A, Valcarce-Pardeiro N, Payeras A, Bernal E, Montero-Alonso M, Yzusqui M, Clotet B, Videla S, Moltó J, Paredes R
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
Repositorio:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
OAI Identifier:oai:isabial.fundanetsuite.com:p9960
Acceso en línea:https://isabial.portalinvestigacion.com/publicaciones9960
https://academic.oup.com/ofid/article/10/11/ofad542/7334398
Access Level:acceso abierto
Palabra clave:darunavir/cobicistat
dolutegravir
multidrug resistance HIV-1
switch strategy
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spelling A Randomized Trial of Dolutegravir Plus Darunavir/Cobicistat as a Switch Strategy in HIV-1-Infected Patients With Resistance to at Least 2 Antiretroviral Classes.Santos JRDomingo PPortilla JGutiérrez FImaz AVilchez HCurran AValcarce-Pardeiro NPayeras ABernal EMontero-Alonso MYzusqui MClotet BVidela SMoltó JParedes Rdarunavir/cobicistatdolutegravirmultidrug resistance HIV-1switch strategyBACKGROUND: Suppressed patients with drug-resistant HIV-1 require effective and simple antiretroviral therapy to maintain treatment adherence and viral suppression. METHODS: This randomized, open-label, noninferiority, multicenter pilot study involved HIV-infected adults who met the following criteria: confirmed HIV-1 RNA <50 copies/mL for =6 months preceding the study randomization, treatment with at least 3 antiretroviral drugs, and a history of drug resistance mutations against at least 2 antiretroviral classes but remaining fully susceptible to darunavir (DRV) and integrase inhibitors. Participants were randomized 1:1 to switch to dolutegravir (DTG; 50 mg once per day) plus DRV boosted with cobicistat (DRV/c; 800/150 mg once per day; 2D group) or continue with their baseline regimen (standard-of-care [SOC] group). The primary endpoint was the proportion of patients with HIV-1 RNA <50 copies/mL at week 48 relative to time to loss of virologic response, with a noninferiority margin set at -12.5%. Virologic failure was defined as confirmed HIV-1 RNA =50 copies/mL or a single determination of HIV-1 RNA >50 copies/mL followed by antiretroviral therapy discontinuation. RESULTS: Forty-five participants were assigned to the 2D group and 44 to the SOC group. Time to loss of virologic response showed no difference in the proportion maintaining HIV-1 RNA <50 copies/mL at week 48: 39 of 45 (86.7%; 95% CI, 73.21%-94.95%) in the 2D group vs 42 of 44 (95.4%; 95% CI, 84.53%-99.44%) in the SOC group (log-rank P = .159) with an estimated difference of -8.7 (95% CI, -22.72 to 5.14). Only 2 (4.5%) in the SOC group experienced virologic failure, and 3 participants from the 2D group experienced adverse events leading to treatment discontinuation. CONCLUSIONS: In suppressed patients with at least 2 resistant antiretroviral classes, noninferiority could not be demonstrated by fully active DRV/c plus DTG. Nevertheless, there were no unexpected adverse events or virologic failure. DRV/c plus DTG may be considered a once-daily therapy option only for well-selected patients. Clinical Trials Registration. ClinicalTrials.gov (NCT03683524).OXFORD UNIV PRESS INC2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://isabial.portalinvestigacion.com/publicaciones9960https://academic.oup.com/ofid/article/10/11/ofad542/7334398Open Forum Infectious DiseasesISSN: 23288957reponame:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicanteinstname:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)Inglésinfo:eu-repo/semantics/openAccessoai:isabial.fundanetsuite.com:p99602026-06-12T10:20:37Z
dc.title.none.fl_str_mv A Randomized Trial of Dolutegravir Plus Darunavir/Cobicistat as a Switch Strategy in HIV-1-Infected Patients With Resistance to at Least 2 Antiretroviral Classes.
title A Randomized Trial of Dolutegravir Plus Darunavir/Cobicistat as a Switch Strategy in HIV-1-Infected Patients With Resistance to at Least 2 Antiretroviral Classes.
spellingShingle A Randomized Trial of Dolutegravir Plus Darunavir/Cobicistat as a Switch Strategy in HIV-1-Infected Patients With Resistance to at Least 2 Antiretroviral Classes.
Santos JR
darunavir/cobicistat
dolutegravir
multidrug resistance HIV-1
switch strategy
title_short A Randomized Trial of Dolutegravir Plus Darunavir/Cobicistat as a Switch Strategy in HIV-1-Infected Patients With Resistance to at Least 2 Antiretroviral Classes.
title_full A Randomized Trial of Dolutegravir Plus Darunavir/Cobicistat as a Switch Strategy in HIV-1-Infected Patients With Resistance to at Least 2 Antiretroviral Classes.
title_fullStr A Randomized Trial of Dolutegravir Plus Darunavir/Cobicistat as a Switch Strategy in HIV-1-Infected Patients With Resistance to at Least 2 Antiretroviral Classes.
title_full_unstemmed A Randomized Trial of Dolutegravir Plus Darunavir/Cobicistat as a Switch Strategy in HIV-1-Infected Patients With Resistance to at Least 2 Antiretroviral Classes.
title_sort A Randomized Trial of Dolutegravir Plus Darunavir/Cobicistat as a Switch Strategy in HIV-1-Infected Patients With Resistance to at Least 2 Antiretroviral Classes.
dc.creator.none.fl_str_mv Santos JR
Domingo P
Portilla J
Gutiérrez F
Imaz A
Vilchez H
Curran A
Valcarce-Pardeiro N
Payeras A
Bernal E
Montero-Alonso M
Yzusqui M
Clotet B
Videla S
Moltó J
Paredes R
author Santos JR
author_facet Santos JR
Domingo P
Portilla J
Gutiérrez F
Imaz A
Vilchez H
Curran A
Valcarce-Pardeiro N
Payeras A
Bernal E
Montero-Alonso M
Yzusqui M
Clotet B
Videla S
Moltó J
Paredes R
author_role author
author2 Domingo P
Portilla J
Gutiérrez F
Imaz A
Vilchez H
Curran A
Valcarce-Pardeiro N
Payeras A
Bernal E
Montero-Alonso M
Yzusqui M
Clotet B
Videla S
Moltó J
Paredes R
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv darunavir/cobicistat
dolutegravir
multidrug resistance HIV-1
switch strategy
topic darunavir/cobicistat
dolutegravir
multidrug resistance HIV-1
switch strategy
description BACKGROUND: Suppressed patients with drug-resistant HIV-1 require effective and simple antiretroviral therapy to maintain treatment adherence and viral suppression. METHODS: This randomized, open-label, noninferiority, multicenter pilot study involved HIV-infected adults who met the following criteria: confirmed HIV-1 RNA <50 copies/mL for =6 months preceding the study randomization, treatment with at least 3 antiretroviral drugs, and a history of drug resistance mutations against at least 2 antiretroviral classes but remaining fully susceptible to darunavir (DRV) and integrase inhibitors. Participants were randomized 1:1 to switch to dolutegravir (DTG; 50 mg once per day) plus DRV boosted with cobicistat (DRV/c; 800/150 mg once per day; 2D group) or continue with their baseline regimen (standard-of-care [SOC] group). The primary endpoint was the proportion of patients with HIV-1 RNA <50 copies/mL at week 48 relative to time to loss of virologic response, with a noninferiority margin set at -12.5%. Virologic failure was defined as confirmed HIV-1 RNA =50 copies/mL or a single determination of HIV-1 RNA >50 copies/mL followed by antiretroviral therapy discontinuation. RESULTS: Forty-five participants were assigned to the 2D group and 44 to the SOC group. Time to loss of virologic response showed no difference in the proportion maintaining HIV-1 RNA <50 copies/mL at week 48: 39 of 45 (86.7%; 95% CI, 73.21%-94.95%) in the 2D group vs 42 of 44 (95.4%; 95% CI, 84.53%-99.44%) in the SOC group (log-rank P = .159) with an estimated difference of -8.7 (95% CI, -22.72 to 5.14). Only 2 (4.5%) in the SOC group experienced virologic failure, and 3 participants from the 2D group experienced adverse events leading to treatment discontinuation. CONCLUSIONS: In suppressed patients with at least 2 resistant antiretroviral classes, noninferiority could not be demonstrated by fully active DRV/c plus DTG. Nevertheless, there were no unexpected adverse events or virologic failure. DRV/c plus DTG may be considered a once-daily therapy option only for well-selected patients. Clinical Trials Registration. ClinicalTrials.gov (NCT03683524).
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://isabial.portalinvestigacion.com/publicaciones9960
https://academic.oup.com/ofid/article/10/11/ofad542/7334398
url https://isabial.portalinvestigacion.com/publicaciones9960
https://academic.oup.com/ofid/article/10/11/ofad542/7334398
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv OXFORD UNIV PRESS INC
publisher.none.fl_str_mv OXFORD UNIV PRESS INC
dc.source.none.fl_str_mv Open Forum Infectious Diseases
ISSN: 23288957
reponame:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
instname:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
instname_str Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
reponame_str r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
collection r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
repository.name.fl_str_mv
repository.mail.fl_str_mv
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