Abstract

Background: Demonstrating durable viral suppression after switching to dolutegravir/lamivudine in clinical practice solidifies its use. Methods: This was a prospective cohort (DUALING) study conducted in 24 Dutch HIV treatment centers. HIV-RNA-suppressed cases undergoing triple-drug antiretroviral therapy without prior virological failure or resistance who switched to dolutegravir/lamivudine (cases) were 1:2 matched to controls, who remained on triple-drug antiretroviral therapy. Matching was stratified by dolutegravir use in the triple-drug antiretroviral therapy, and further by age, sex, HIV acquisition route, CD4+T-cell nadir, and HIV-RNA zenith. The primary endpoint was the treatment failure rate at 2 years, determined using intention-to-treat and on-treatment analyses with a 5% noninferiority margin. Results: The 2040 mostly male (84.3%) participants included 390 cases of dolutegravir-based triple-drug regimens with 680 controls, and 290 cases of non-dolutegravir-based triple-drug regimens with 580 controls. In the dolutegravir-based cases and controls, treatment failure occurred in 12.6% and 23.3% of patients in the intention-to-treat analysis (difference: −10.7%, 95%CI: −15.3% to −6.1%) and 2.6% and 2.4% of patients in the on-treatment analysis (difference: +0.2%, 95%CI −1.9% to +2.3%). The treatment failure risk in non-dolutegravir-based cases and controls was 15.2% and 19.9% in the intention-to-treat analysis (difference: −4.7, 95%CI: −10.0% to +0.6%) and 1.2% and 1.9% in the on-treatment analysis (difference +0.7%, 95%CI −2.6% to +1.1%). Therapy modifications unrelated to virological failure explained the higher treatment failure rate in the intention-to-treat analysis. In dolutegravir/lamivudine cases, a shorter time of prior triple-drug antiretroviral therapy, age < 50 years, and non-Western origin were associated with treatment failure in the multivariable analysis. Viral blips occurred in 6.8% of cases and 5.1% of controls. In the post hoc analysis, discontinuing tenofovir disoproxil fumarate-based triple-drug antiretroviral therapy led to weight gain in people with (+2.7 kg) and without (+2.3 kg) prior dolutegravir use. Conclusions: In this nationwide clinical practice study, switching to dolutegravir/lamivudine was noninferior to continuing triple-drug antiretroviral therapy after 2 years of follow-up.

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