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Efficacy and safety of dolutegravir plus emtricitabine versus standard ART for the maintenance of HIV-1 suppression: 48-week results of the factorial, randomized, non-inferiority SIMPL’HIV trial

BACKGROUND: Dolutegravir (DTG)–based dual therapy is becoming a new paradigm for both the initiation and maintenance of HIV treatment. The SIMPL’HIV study investigated the outcomes of virologically suppressed patients on standard combination antiretroviral therapy (cART) switching to DTG + emtricita...

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Autores principales: Sculier, Delphine, Wandeler, Gilles, Yerly, Sabine, Marinosci, Annalisa, Stoeckle, Marcel, Bernasconi, Enos, Braun, Dominique L., Vernazza, Pietro, Cavassini, Matthias, Buzzi, Marta, Metzner, Karin J., Decosterd, Laurent A., Günthard, Huldrych F., Schmid, Patrick, Limacher, Andreas, Egger, Matthias, Calmy, Alexandra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654764/
https://www.ncbi.nlm.nih.gov/pubmed/33170863
http://dx.doi.org/10.1371/journal.pmed.1003421
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author Sculier, Delphine
Wandeler, Gilles
Yerly, Sabine
Marinosci, Annalisa
Stoeckle, Marcel
Bernasconi, Enos
Braun, Dominique L.
Vernazza, Pietro
Cavassini, Matthias
Buzzi, Marta
Metzner, Karin J.
Decosterd, Laurent A.
Günthard, Huldrych F.
Schmid, Patrick
Limacher, Andreas
Egger, Matthias
Calmy, Alexandra
author_facet Sculier, Delphine
Wandeler, Gilles
Yerly, Sabine
Marinosci, Annalisa
Stoeckle, Marcel
Bernasconi, Enos
Braun, Dominique L.
Vernazza, Pietro
Cavassini, Matthias
Buzzi, Marta
Metzner, Karin J.
Decosterd, Laurent A.
Günthard, Huldrych F.
Schmid, Patrick
Limacher, Andreas
Egger, Matthias
Calmy, Alexandra
author_sort Sculier, Delphine
collection PubMed
description BACKGROUND: Dolutegravir (DTG)–based dual therapy is becoming a new paradigm for both the initiation and maintenance of HIV treatment. The SIMPL’HIV study investigated the outcomes of virologically suppressed patients on standard combination antiretroviral therapy (cART) switching to DTG + emtricitabine (FTC). We present the 48-week efficacy and safety data on DTG + FTC versus cART. METHODS AND FINDINGS: SIMPL’HIV was a multicenter, open-label, non-inferiority randomized trial with a factorial design among treatment-experienced people with HIV in Switzerland. Participants were enrolled between 12 May 2017 and 30 May 2018. Patients virologically suppressed for at least 24 weeks on standard cART were randomized 1:1 to switching to DTG + FTC or to continuing cART, and 1:1 to simplified patient-centered monitoring versus standard monitoring. The primary endpoint was the proportion of patients virologically suppressed with <100 copies/ml through 48 weeks. The secondary endpoints included virological suppression at 48 weeks according to the US Food and Drug Administration (FDA) snapshot analysis. Non-inferiority of DTG + FTC versus cART for viral suppression was assessed using a stratified Mantel–Haenszel risk difference, with non-inferiority declared if the lower bound of the 95% confidence interval was greater than −12%. Adverse events were monitored to assess safety. Quality of life was evaluated using the PROQOL-HIV questionnaire. Ninety-three participants were randomized to DTG + FTC, and 94 individuals to cART. Median nadir CD4 count was 246 cells/mm(3); median age was 48 years; 17% of participants were female. DTG + FTC was non-inferior to cART. The proportion of patients with viral suppression (<100 copies/ml) through 48 weeks was 93.5% in the DTG + FTC arm and 94.7% in the cART arm in the intention-to-treat population (risk difference −1.2%; 95% CI −7.8% to 5.6%). Per-protocol analysis showed similar results, with viral suppression in 96.5% of patients in both arms (risk difference 0.0%; 95% CI −5.6% to 5.5%). There was no relevant interaction between the type of treatment and monitoring (interaction ratio 0.98; 95% CI 0.85 to 1.13; p = 0.81). Using the FDA snapshot algorithm, 84/93 (90.3%) participants in the DTG + FTC arm had an HIV-1 RNA viral load of <50 copies/ml compared to 86/94 (91.5%) participants on standard cART (risk difference −1.1%; 95% CI −9.3% to 7.1%; p = 0.791). The overall proportion of patients with adverse events and discontinuations did not differ by randomization arm. The proportion of patients with serious adverse events was higher in the cART arm (16%) compared to the DTG + FTC arm (6.5%) (p = 0.041), but none was considered to be related to the study medication. Quality of life improved more between baseline and week 48 in the DTG + FTC compared to the cART arm (adjusted difference +2.6; 95% CI +0.4 to +4.7). The study’s main limitations included a rather small proportion of women included, the open label design, and its short duration. CONCLUSIONS: In this study, DTG + FTC as maintenance therapy was non-inferior to cART in terms of efficacy, with a similar safety profile and a greater improvement in quality of life, thus expanding the offer of 2-drug simplification options among virologically suppressed individuals. TRIAL REGISTRATION: ClinicalTrials.gov NCT03160105.
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spelling pubmed-76547642020-11-18 Efficacy and safety of dolutegravir plus emtricitabine versus standard ART for the maintenance of HIV-1 suppression: 48-week results of the factorial, randomized, non-inferiority SIMPL’HIV trial Sculier, Delphine Wandeler, Gilles Yerly, Sabine Marinosci, Annalisa Stoeckle, Marcel Bernasconi, Enos Braun, Dominique L. Vernazza, Pietro Cavassini, Matthias Buzzi, Marta Metzner, Karin J. Decosterd, Laurent A. Günthard, Huldrych F. Schmid, Patrick Limacher, Andreas Egger, Matthias Calmy, Alexandra PLoS Med Research Article BACKGROUND: Dolutegravir (DTG)–based dual therapy is becoming a new paradigm for both the initiation and maintenance of HIV treatment. The SIMPL’HIV study investigated the outcomes of virologically suppressed patients on standard combination antiretroviral therapy (cART) switching to DTG + emtricitabine (FTC). We present the 48-week efficacy and safety data on DTG + FTC versus cART. METHODS AND FINDINGS: SIMPL’HIV was a multicenter, open-label, non-inferiority randomized trial with a factorial design among treatment-experienced people with HIV in Switzerland. Participants were enrolled between 12 May 2017 and 30 May 2018. Patients virologically suppressed for at least 24 weeks on standard cART were randomized 1:1 to switching to DTG + FTC or to continuing cART, and 1:1 to simplified patient-centered monitoring versus standard monitoring. The primary endpoint was the proportion of patients virologically suppressed with <100 copies/ml through 48 weeks. The secondary endpoints included virological suppression at 48 weeks according to the US Food and Drug Administration (FDA) snapshot analysis. Non-inferiority of DTG + FTC versus cART for viral suppression was assessed using a stratified Mantel–Haenszel risk difference, with non-inferiority declared if the lower bound of the 95% confidence interval was greater than −12%. Adverse events were monitored to assess safety. Quality of life was evaluated using the PROQOL-HIV questionnaire. Ninety-three participants were randomized to DTG + FTC, and 94 individuals to cART. Median nadir CD4 count was 246 cells/mm(3); median age was 48 years; 17% of participants were female. DTG + FTC was non-inferior to cART. The proportion of patients with viral suppression (<100 copies/ml) through 48 weeks was 93.5% in the DTG + FTC arm and 94.7% in the cART arm in the intention-to-treat population (risk difference −1.2%; 95% CI −7.8% to 5.6%). Per-protocol analysis showed similar results, with viral suppression in 96.5% of patients in both arms (risk difference 0.0%; 95% CI −5.6% to 5.5%). There was no relevant interaction between the type of treatment and monitoring (interaction ratio 0.98; 95% CI 0.85 to 1.13; p = 0.81). Using the FDA snapshot algorithm, 84/93 (90.3%) participants in the DTG + FTC arm had an HIV-1 RNA viral load of <50 copies/ml compared to 86/94 (91.5%) participants on standard cART (risk difference −1.1%; 95% CI −9.3% to 7.1%; p = 0.791). The overall proportion of patients with adverse events and discontinuations did not differ by randomization arm. The proportion of patients with serious adverse events was higher in the cART arm (16%) compared to the DTG + FTC arm (6.5%) (p = 0.041), but none was considered to be related to the study medication. Quality of life improved more between baseline and week 48 in the DTG + FTC compared to the cART arm (adjusted difference +2.6; 95% CI +0.4 to +4.7). The study’s main limitations included a rather small proportion of women included, the open label design, and its short duration. CONCLUSIONS: In this study, DTG + FTC as maintenance therapy was non-inferior to cART in terms of efficacy, with a similar safety profile and a greater improvement in quality of life, thus expanding the offer of 2-drug simplification options among virologically suppressed individuals. TRIAL REGISTRATION: ClinicalTrials.gov NCT03160105. Public Library of Science 2020-11-10 /pmc/articles/PMC7654764/ /pubmed/33170863 http://dx.doi.org/10.1371/journal.pmed.1003421 Text en © 2020 Sculier et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Sculier, Delphine
Wandeler, Gilles
Yerly, Sabine
Marinosci, Annalisa
Stoeckle, Marcel
Bernasconi, Enos
Braun, Dominique L.
Vernazza, Pietro
Cavassini, Matthias
Buzzi, Marta
Metzner, Karin J.
Decosterd, Laurent A.
Günthard, Huldrych F.
Schmid, Patrick
Limacher, Andreas
Egger, Matthias
Calmy, Alexandra
Efficacy and safety of dolutegravir plus emtricitabine versus standard ART for the maintenance of HIV-1 suppression: 48-week results of the factorial, randomized, non-inferiority SIMPL’HIV trial
title Efficacy and safety of dolutegravir plus emtricitabine versus standard ART for the maintenance of HIV-1 suppression: 48-week results of the factorial, randomized, non-inferiority SIMPL’HIV trial
title_full Efficacy and safety of dolutegravir plus emtricitabine versus standard ART for the maintenance of HIV-1 suppression: 48-week results of the factorial, randomized, non-inferiority SIMPL’HIV trial
title_fullStr Efficacy and safety of dolutegravir plus emtricitabine versus standard ART for the maintenance of HIV-1 suppression: 48-week results of the factorial, randomized, non-inferiority SIMPL’HIV trial
title_full_unstemmed Efficacy and safety of dolutegravir plus emtricitabine versus standard ART for the maintenance of HIV-1 suppression: 48-week results of the factorial, randomized, non-inferiority SIMPL’HIV trial
title_short Efficacy and safety of dolutegravir plus emtricitabine versus standard ART for the maintenance of HIV-1 suppression: 48-week results of the factorial, randomized, non-inferiority SIMPL’HIV trial
title_sort efficacy and safety of dolutegravir plus emtricitabine versus standard art for the maintenance of hiv-1 suppression: 48-week results of the factorial, randomized, non-inferiority simpl’hiv trial
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654764/
https://www.ncbi.nlm.nih.gov/pubmed/33170863
http://dx.doi.org/10.1371/journal.pmed.1003421
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