Dolutegravir/Lamivudine Is Noninferior to Continuing Dolutegravir- and Non-Dolutegravir-Based Triple-Drug Antiretroviral Therapy in Virologically Suppressed People With Human Immunodeficiency Virus: DUALING Prospective Nationwide Matched Cohort Study.

Autor: Vasylyev M; Section of Infectious Diseases, Department of Internal Medicine, and Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center, Rotterdam, The Netherlands., Wit FWNM; Stichting HIV Monitoring, Amsterdam, The Netherlands., Jordans CCE; Section of Infectious Diseases, Department of Internal Medicine, and Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center, Rotterdam, The Netherlands., Soetekouw R; Department of Internal Medicine, Spaarne Gasthuis, Haarlem/Hoofddorp, The Netherlands., van Lelyveld SFL; Department of Internal Medicine, Spaarne Gasthuis, Haarlem/Hoofddorp, The Netherlands., Kootstra GJ; Department of Internal Medicine, Medisch Spectrum Twente, Enschede, The Netherlands., Delsing CE; Department of Internal Medicine, Medisch Spectrum Twente, Enschede, The Netherlands., Ammerlaan HSM; Department of Internal Medicine, Catharina Ziekenhuis Eindhoven, Eindhoven, The Netherlands., van Kasteren MEE; Department of Internal Medicine, Elisabeth Tweesteden Ziekenhuis, Tilburg, The Netherlands., Brouwer AE; Department of Internal Medicine, Elisabeth Tweesteden Ziekenhuis, Tilburg, The Netherlands., Leyten EMS; Department of Internal Medicine, Haaglanden Medisch Centrum, The Hague, The Netherlands., Claassen MAA; Department of Internal Medicine, Rijnstate Ziekenhuis, Arnhem, The Netherlands., Hassing RJ; Department of Internal Medicine, Rijnstate Ziekenhuis, Arnhem, The Netherlands., den Hollander JG; Department of Internal Medicine, Maasstadziekenhuis, Rotterdam, The Netherlands., van den Berge M; Department of Internal Medicine, Admiraal de Ruyter Ziekenhuis, Vlissingen, The Netherlands., Roukens AHE; Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands., Bierman WFW; Section of Infectious Diseases, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Groeneveld PHP; Department of Internal Medicine, Isala, Zwolle, The Netherlands., Lowe SH; Infectious Diseases and Infection Prevention, Department of Internal Medicine and Department of Medical Microbiology, Maastricht University Medical Center, Maastricht, The Netherlands., van Welzen BJ; Department of Internal Medicine, University Medical Center Utrecht, Utrecht, The Netherlands., Richel O; Section of Infectious Diseases, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands., Nellen JF; Amsterdam Infection and Immunity Institute, Department of Infectious Diseases, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands., van den Berk GEL; Department of Internal Medicine, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands., van der Valk M; Stichting HIV Monitoring, Amsterdam, The Netherlands.; Amsterdam Infection and Immunity Institute, Department of Infectious Diseases, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands., Rijnders BJA; Section of Infectious Diseases, Department of Internal Medicine, and Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center, Rotterdam, The Netherlands., Rokx C; Section of Infectious Diseases, Department of Internal Medicine, and Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center, Rotterdam, The Netherlands.
Jazyk: angličtina
Zdroj: Open forum infectious diseases [Open Forum Infect Dis] 2024 Mar 18; Vol. 11 (4), pp. ofae160. Date of Electronic Publication: 2024 Mar 18 (Print Publication: 2024).
DOI: 10.1093/ofid/ofae160
Abstrakt: Background: Confirming the efficacy of dolutegravir/lamivudine in clinical practice solidifies recommendations on its use.
Methods: Prospective cohort study (DUALING) in 24 human immunodeficiency virus (HIV) treatment centers in the Netherlands. HIV RNA-suppressed cases were on triple-drug antiretroviral regimens without prior virological failure or resistance and started dolutegravir/lamivudine. Cases were 1:2 matched to controls on triple-drug antiretroviral regimens by the use of dolutegravir-based regimens, age, sex, transmission route, CD4 + T-cell nadir, and HIV RNA zenith. The primary endpoint was the treatment failure rate in cases versus controls at 1 year by intention-to-treat and on-treatment analyses with 5% noninferiority margin.
Results: The 2040 participants were 680 cases and 1380 controls. Treatment failure in the 390 dolutegravir-based cases versus controls occurred in 8.72% and 12.50% (difference: -3.78% [95% confidence interval {CI}, -7.49% to .08%]) by intention-to-treat and 1.39% and 0.80% (difference: 0.59% [95% CI, -.80% to 1.98%]) by on-treatment analyses. The treatment failure risk in 290 non-dolutegravir-based cases was also noninferior to controls. Antiretroviral regimen modifications unrelated to virological failure explained the higher treatment failure rate by intention-to-treat. A shorter time on triple-drug antiretroviral therapy and being of non-Western origin was associated with treatment failure. Treatment failure, defined as 2 consecutive HIV RNA >50 copies/mL, occurred in 4 cases and 5 controls but without genotypic resistance detected. Viral blips occured comparable in cases and controls but cases gained more weight, especially when tenofovir-based regimens were discontinued.
Conclusions: In routine care, dolutegravir/lamivudine was noninferior to continuing triple-drug antiretroviral regimens after 1 year, supporting the use of dolutegravir/lamivudine in clinical practice.
Clinical Trials Registration: NCT04707326.
Competing Interests: Potential conflicts of interest. F. W. N. M. W. reports consulting fees from ViiV Healthcare. C. R. reports research grants, travel reimbursement, and compensation for participation in scientific boards from ViiV Healthcare and Gilead Sciences. B. J. A. R. reports consulting fees from ViiV Healthcare, Gilead Sciences, and MSD and compensation for educational activities from ViiV Healthcare. M. v. d. V. reports research grants and consulting fees from Gilead Sciences, ViiV Healthcare, and MSD, all paid to his institution. C. C. E. J. reports travel reimbursement from Gilead Sciences and compensation for presentation from ViiV Healthcare. S. v. L. reports a research grant from Pfizer outside the context of this study. J. G. d. H. reports compensation for participation in scientific boards from ViiV Healthcare, Gilead Sciences, Moderna, and GSK. B. J. v. W. reports a research grant from Gilead Sciences, consulting fees from ViiV Healthcare and Gilead Sciences, compensation for participation on a data and safety monitoring board from ViiV Healthcare and Gilead Sciences, and payment for lectures from Gilead Sciences. J. F. N. reports compensation for educational activities and participation in scientific advisory boards from Gilead Sciences, ViiV Healthcare, and MSD, all paid to her institution. All other authors report no potential conflicts.
(© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
Databáze: MEDLINE
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