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Clinical Trial
. 2024 Mar 18;11(4):ofae160.
doi: 10.1093/ofid/ofae160. eCollection 2024 Apr.

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

Marta Vasylyev  1 , Ferdinand W N M Wit  2 , Carlijn C E Jordans  1 , Robin Soetekouw  3 , Steven F L van Lelyveld  3 , Gert-Jan Kootstra  4 , Corine E Delsing  4 , Heidi S M Ammerlaan  5 , Marjo E E van Kasteren  6 , Annemarie E Brouwer  6 , Eliane M S Leyten  7 , Mark A A Claassen  8 , Robert-Jan Hassing  8 , Jan G den Hollander  9 , Marcel van den Berge  10 , Anna H E Roukens  11 , Wouter F W Bierman  12 , Paul H P Groeneveld  13 , Selwyn H Lowe  14 , Berend J van Welzen  15 , Olivier Richel  16 , Jeannine F Nellen  17 , Guido E L van den Berk  18 , Marc van der Valk  2   17 , Bart J A Rijnders  1 , Casper Rokx  1
Affiliations
Clinical Trial

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

Marta Vasylyev et al. Open Forum Infect Dis. .

Abstract

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.

Keywords: 2DR; HIV; dolutegravir; lamivudine; real-world; virological failure.

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Conflict of interest statement

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.

Figures

Figure 1.
Figure 1.
Treatment failure risk difference with 1-sided 90% confidence interval (CI) between cases on dolutegravir/lamivudine and controls on triple-drug antiretroviral regimens. Treatment failure risk difference with 1-sided 90% CI at 1 year of follow-up between cases and controls who were virologically suppressed on either a dolutegravir- or a non-dolutegravir-containing triple-drug antiretroviral regimen and started dolutegravir/lamivudine or continued triple-drug antiretroviral regimens by on-treatment and intention-to-treat analysis. The vertical red dotted line indicates the 5% noninferiority margin. Abbreviations: 3TC, lamivudine; DTG, dolutegravir; OT, on-treatment; ITT, intention-to-treat.
Figure 2.
Figure 2.
Treatment failure risk difference with 2-sided 95% confidence interval (CI) between cases on dolutegravir/lamivudine and controls on triple-drug antiretroviral regimens. Treatment failure risk difference with 2-sided 95% CI at 1 year of follow-up between cases and controls who were virologically suppressed on either a dolutegravir- or a non-dolutegravir-containing triple-drug antiretroviral regimen and started dolutegravir/lamivudine or continued triple-drug antiretroviral regimens by on-treatment and intention-to-treat analysis. The vertical red dotted line indicates the 5% noninferiority margin. Abbreviations: 3TC, lamivudine; CI, confidence interval; DTG, dolutegravir; OT, on-treatment; ITT, intention-to-treat.
Figure 3.
Figure 3.
Treatment success rate in cases on dolutegravir/lamivudine and controls on triple-drug antiretroviral regimens. Treatment success rate at 1 year of follow-up in the on-treatment and intention-to-treat population between cases and controls who were virologically suppressed on either a dolutegravir- or a non-dolutegravir-containing triple-drug antiretroviral regimen and started dolutegravir/lamivudine or continued triple-drug antiretroviral regimens. Abbreviations: 3TC, lamivudine; DTG, dolutegravir; OT, on-treatment; ITT, intention-to-treat.
Figure 4.
Figure 4.
Subgroup analysis of treatment failure at 1 year of follow-up in 680 cases on dolutegravir/lamivudine. Square markers denote the odds ratio (OR). The vertical dashed line at OR = 1 is the line of no effect. Upper calipers are capped at value 4.5. The reference category uses open square markers at OR = 1. Abbreviations: 3TC, lamivudine; ART, antiretroviral therapy; CI, confidence interval; DTG, dolutegravir; HIV, human immunodeficiency virus; MSM, men who have sex with men; OR, odds ratio; PWH, people with human immunodeficiency virus.
Figure 5.
Figure 5.
Subgroup analysis of treatment failure at 1 year of follow-up in 1380 controls continuing triple-drug antiretroviral therapy. Square markers denote the odds ratio (OR). The vertical dashed line at OR = 1 is the line of no effect. Upper calipers are capped at value 4.5. The reference category uses open square markers at OR = 1. Abbreviations: ART, antiretroviral therapy; CI, confidence interval; DTG, dolutegravir; HIV, human immunodeficiency virus; MSM, men who have sex with men; OR, odds ratio; PWH, people with human immunodeficiency virus.
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