TY - JOUR
T1 - Dolutegravir/Lamivudine Is Noninferior to Continuing Dolutegravir- and Non-Dolutegravir-Based Triple-Drug Antiretroviral Therapy in Virologically Suppressed People With Human Immunodeficiency Virus
T2 - DUALING Prospective Nationwide Matched Cohort Study
AU - Vasylyev, Marta
AU - Wit, Ferdinand W.N.M.
AU - Jordans, Carlijn C.E.
AU - Soetekouw, Robin
AU - van Lelyveld, Steven F.L.
AU - Kootstra, Gert Jan
AU - Delsing, Corine E.
AU - Ammerlaan, Heidi S.M.
AU - van Kasteren, Marjo E.E.
AU - Brouwer, Annemarie E.
AU - Leyten, Eliane M.S.
AU - Claassen, Mark A.A.
AU - Hassing, Robert Jan
AU - den Hollander, Jan G.
AU - van den Berge, Marcel
AU - Roukens, Anna H.E.
AU - Bierman, Wouter F.W.
AU - Groeneveld, Paul H.P.
AU - Lowe, Selwyn H.
AU - van Welzen, Berend J.
AU - Richel, Olivier
AU - Nellen, Jeannine F.
AU - van den Berk, Guido E.L.
AU - van der Valk, Marc
AU - Rijnders, Bart J.A.
AU - Rokx, Casper
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/4/1
Y1 - 2024/4/1
N2 - 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.
AB - 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.
KW - 2DR
KW - dolutegravir
KW - HIV
KW - lamivudine
KW - real-world
KW - virological failure
UR - http://www.scopus.com/inward/record.url?scp=85189554853&partnerID=8YFLogxK
U2 - 10.1093/ofid/ofae160
DO - 10.1093/ofid/ofae160
M3 - Article
AN - SCOPUS:85189554853
SN - 2328-8957
VL - 11
JO - Open Forum Infectious Diseases
JF - Open Forum Infectious Diseases
IS - 4
M1 - ofae160
ER -