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Efficacy and Safety of Switching to the 2-Drug Regimen Dolutegravir/Lamivudine Versus Continuing a 3- or 4-Drug Regimen for Maintaining Virologic Suppression in Adults Living With Human Immunodeficiency Virus 1 (HIV-1): Week 48 Results From the Phase 3, Noninferiority SALSA Randomized Trial
BACKGROUND: In TANGO, switching to dolutegravir/lamivudine (DTG/3TC) demonstrated long-term noninferior efficacy vs continuing tenofovir alafenamide–based regimens in treatment-experienced adults with HIV-1. The phase 3 SALSA study evaluated efficacy and safety of switching to DTG/3TC compared with...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10021070/ https://www.ncbi.nlm.nih.gov/pubmed/35235656 http://dx.doi.org/10.1093/cid/ciac130 |
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author | Llibre, Josep M Brites, Carlos Cheng, Chien-Yu Osiyemi, Olayemi Galera, Carlos Hocqueloux, Laurent Maggiolo, Franco Degen, Olaf Taylor, Stephen Blair, Elizabeth Man, Choy Wynne, Brian Oyee, James Underwood, Mark Curtis, Lloyd Bontempo, Gilda van Wyk, Jean |
author_facet | Llibre, Josep M Brites, Carlos Cheng, Chien-Yu Osiyemi, Olayemi Galera, Carlos Hocqueloux, Laurent Maggiolo, Franco Degen, Olaf Taylor, Stephen Blair, Elizabeth Man, Choy Wynne, Brian Oyee, James Underwood, Mark Curtis, Lloyd Bontempo, Gilda van Wyk, Jean |
author_sort | Llibre, Josep M |
collection | PubMed |
description | BACKGROUND: In TANGO, switching to dolutegravir/lamivudine (DTG/3TC) demonstrated long-term noninferior efficacy vs continuing tenofovir alafenamide–based regimens in treatment-experienced adults with HIV-1. The phase 3 SALSA study evaluated efficacy and safety of switching to DTG/3TC compared with continuing various 3-/4-drug current antiretroviral regimens (CARs). METHODS: Adults with HIV-1 RNA <50 copies/mL and no previous virologic failure were randomized (1:1, stratified by baseline third agent class) to switch to once-daily fixed-dose combination DTG/3TC or continue CAR (primary endpoint: proportion of participants with HIV-1 RNA ≥50 copies/mL at week 48; Snapshot, intention-to-treat–exposed population, 5% noninferiority margin). RESULTS: Overall, 493 adults (39% women; 39% aged ≥50 years; 19% African American/African heritage; 14% Asian) were randomized to switch to DTG/3TC (n = 246) or continue CAR (n = 247). At week 48, 1 (0.4%) participant in the DTG/3TC group and 3 (1.2%) in the CAR group had HIV-1 RNA ≥50 copies/mL (Snapshot), demonstrating noninferiority (adjusted difference, −0.8%; 95% CI, −2.4%, .8%). Zero participants met confirmed virologic withdrawal criteria; therefore, no resistance testing was performed. Drug-related adverse events were more frequent with DTG/3TC (20%) than CAR (6%) through week 48 but comparable post–week 24 (5% vs 2%, respectively). Proximal tubular renal function and bone turnover biomarkers improved with DTG/3TC. Both groups had generally minimal changes in lipids and inflammatory biomarkers. CONCLUSIONS: Switching to DTG/3TC was noninferior to continuing CAR for maintaining virologic suppression at week 48 with no observed resistance, supporting the efficacy, good safety, and high barrier to resistance of DTG/3TC. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov, NCT04021290. |
format | Online Article Text |
id | pubmed-10021070 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-100210702023-03-18 Efficacy and Safety of Switching to the 2-Drug Regimen Dolutegravir/Lamivudine Versus Continuing a 3- or 4-Drug Regimen for Maintaining Virologic Suppression in Adults Living With Human Immunodeficiency Virus 1 (HIV-1): Week 48 Results From the Phase 3, Noninferiority SALSA Randomized Trial Llibre, Josep M Brites, Carlos Cheng, Chien-Yu Osiyemi, Olayemi Galera, Carlos Hocqueloux, Laurent Maggiolo, Franco Degen, Olaf Taylor, Stephen Blair, Elizabeth Man, Choy Wynne, Brian Oyee, James Underwood, Mark Curtis, Lloyd Bontempo, Gilda van Wyk, Jean Clin Infect Dis Major Article BACKGROUND: In TANGO, switching to dolutegravir/lamivudine (DTG/3TC) demonstrated long-term noninferior efficacy vs continuing tenofovir alafenamide–based regimens in treatment-experienced adults with HIV-1. The phase 3 SALSA study evaluated efficacy and safety of switching to DTG/3TC compared with continuing various 3-/4-drug current antiretroviral regimens (CARs). METHODS: Adults with HIV-1 RNA <50 copies/mL and no previous virologic failure were randomized (1:1, stratified by baseline third agent class) to switch to once-daily fixed-dose combination DTG/3TC or continue CAR (primary endpoint: proportion of participants with HIV-1 RNA ≥50 copies/mL at week 48; Snapshot, intention-to-treat–exposed population, 5% noninferiority margin). RESULTS: Overall, 493 adults (39% women; 39% aged ≥50 years; 19% African American/African heritage; 14% Asian) were randomized to switch to DTG/3TC (n = 246) or continue CAR (n = 247). At week 48, 1 (0.4%) participant in the DTG/3TC group and 3 (1.2%) in the CAR group had HIV-1 RNA ≥50 copies/mL (Snapshot), demonstrating noninferiority (adjusted difference, −0.8%; 95% CI, −2.4%, .8%). Zero participants met confirmed virologic withdrawal criteria; therefore, no resistance testing was performed. Drug-related adverse events were more frequent with DTG/3TC (20%) than CAR (6%) through week 48 but comparable post–week 24 (5% vs 2%, respectively). Proximal tubular renal function and bone turnover biomarkers improved with DTG/3TC. Both groups had generally minimal changes in lipids and inflammatory biomarkers. CONCLUSIONS: Switching to DTG/3TC was noninferior to continuing CAR for maintaining virologic suppression at week 48 with no observed resistance, supporting the efficacy, good safety, and high barrier to resistance of DTG/3TC. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov, NCT04021290. Oxford University Press 2022-03-02 /pmc/articles/PMC10021070/ /pubmed/35235656 http://dx.doi.org/10.1093/cid/ciac130 Text en © The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Major Article Llibre, Josep M Brites, Carlos Cheng, Chien-Yu Osiyemi, Olayemi Galera, Carlos Hocqueloux, Laurent Maggiolo, Franco Degen, Olaf Taylor, Stephen Blair, Elizabeth Man, Choy Wynne, Brian Oyee, James Underwood, Mark Curtis, Lloyd Bontempo, Gilda van Wyk, Jean Efficacy and Safety of Switching to the 2-Drug Regimen Dolutegravir/Lamivudine Versus Continuing a 3- or 4-Drug Regimen for Maintaining Virologic Suppression in Adults Living With Human Immunodeficiency Virus 1 (HIV-1): Week 48 Results From the Phase 3, Noninferiority SALSA Randomized Trial |
title | Efficacy and Safety of Switching to the 2-Drug Regimen Dolutegravir/Lamivudine Versus Continuing a 3- or 4-Drug Regimen for Maintaining Virologic Suppression in Adults Living With Human Immunodeficiency Virus 1 (HIV-1): Week 48 Results From the Phase 3, Noninferiority SALSA Randomized Trial |
title_full | Efficacy and Safety of Switching to the 2-Drug Regimen Dolutegravir/Lamivudine Versus Continuing a 3- or 4-Drug Regimen for Maintaining Virologic Suppression in Adults Living With Human Immunodeficiency Virus 1 (HIV-1): Week 48 Results From the Phase 3, Noninferiority SALSA Randomized Trial |
title_fullStr | Efficacy and Safety of Switching to the 2-Drug Regimen Dolutegravir/Lamivudine Versus Continuing a 3- or 4-Drug Regimen for Maintaining Virologic Suppression in Adults Living With Human Immunodeficiency Virus 1 (HIV-1): Week 48 Results From the Phase 3, Noninferiority SALSA Randomized Trial |
title_full_unstemmed | Efficacy and Safety of Switching to the 2-Drug Regimen Dolutegravir/Lamivudine Versus Continuing a 3- or 4-Drug Regimen for Maintaining Virologic Suppression in Adults Living With Human Immunodeficiency Virus 1 (HIV-1): Week 48 Results From the Phase 3, Noninferiority SALSA Randomized Trial |
title_short | Efficacy and Safety of Switching to the 2-Drug Regimen Dolutegravir/Lamivudine Versus Continuing a 3- or 4-Drug Regimen for Maintaining Virologic Suppression in Adults Living With Human Immunodeficiency Virus 1 (HIV-1): Week 48 Results From the Phase 3, Noninferiority SALSA Randomized Trial |
title_sort | efficacy and safety of switching to the 2-drug regimen dolutegravir/lamivudine versus continuing a 3- or 4-drug regimen for maintaining virologic suppression in adults living with human immunodeficiency virus 1 (hiv-1): week 48 results from the phase 3, noninferiority salsa randomized trial |
topic | Major Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10021070/ https://www.ncbi.nlm.nih.gov/pubmed/35235656 http://dx.doi.org/10.1093/cid/ciac130 |
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