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

Abstract

Background Confirming the efficacy of dolutegravir/lamivudine in clinical practice with matched controls on suppressive triple-drug antiretroviral regimens would solidify recommendations on its use. Methods DUALING was a prospective cohort study in 24 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. Follow-up was calendar time-synchronized between matched pairs. The primary endpoint was the treatment failure rate in cases on dolutegravir/lamivudine and controls on continued dolutegravir-based triple-drug antiretroviral regimens at 1 year by intention-to-treat (missing data=failure) and on-treatment analyses with 5% non-inferiority margin. Results The 2040 participants were 680 cases (390 dolutegravir-based and 290 non-dolutegravir-based regimens) and 1380 controls. Treatment failure in the dolutegravir-based cases versus controls occurred in 8.72% and 12.50% (difference:-3.78%, 95%CI:-7.49%-0.08%) by intention-to-treat and 1.39% and 0.80% (difference:0.59% 95%CI:-0.80%-1.98%) by on-treatment analyses. The treatment failure risk in non-dolutegravir-based cases was also non-inferior 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>50copies/mL occurred in 4 cases and 5 controls but without genotypic resistance detected. Other treatment outcomes of clinical interest indicated a comparable low viral blip rate in cases and controls but more weight gain in cases, especially when tenofovir-based regimens were discontinued. Conclusions In routine care, dolutegravir/lamivudine was non-inferior to continuing triple-drug antiretroviral regimens after 1 year. This supports the use of dolutegravir/lamivudine in clinical practice.