Efficacy and Safety of Switching to Dolutegravir With Boosted Darunavir in Virologically Suppressed Adults With HIV-1: A Randomized, Open-Label, Multicenter, Phase 3, Noninferiority Trial: The DUALIS Study

摘要

BackgroundDolutegravir (DTG) and boosted darunavir (bDRV) are potent antiretrovirals with a high resistance barrier and might be valuable switch options for people with HIV (PWH).MethodsDUALIS, a randomized, open-label, phase 3b, noninferiority clinical trial, compared the switch to DTG?+?bDRV (2DR) with continuation of 2 nucleoside reverse transcriptase inhibitors (2NRTI)?+?bDRV (3DR). PWH with HIV RNA?50 copies/mL taking 2NRTI?+?bDRV (3DR) for?≥24 weeks (1 accepted blip?200 copies/mL) were randomized to either switch to DTG 50 mg?+?DRV 800 mg (boosted with 100 mg of ritonavir) or continue taking 3DR. The primary end point (PE) was the proportion of HIV RNA?50 copies/mL at week (W) 48. Change in NRTI backbone was not classified as failure. The estimated sample size for PE analysis was 292; the noninferiority margin was?≤–10.0%.ResultsIn total, 263 subjects were randomized and treated (2DR n?=?131, 3DR n?=?132; 90.1% male; 89.7% Caucasian; median age [interquartile range], 48 [39–54] years). At W48, 86.3% (n?=?113/131) of the 2DR subject and 87.9% (n?=?116/132) of the 3DR subjects had HIV RNA?50 copies/mL; the difference between arms was –1.6% (95.48% CI, based on the adjusted alpha level accounting for the interim analysis at W24, –9.9% to +6.7%; discontinuations due to adverse events: 2DR, 4.6% [n?=?6]; 3DR, 0.8% [n?=?1]). Kaplan-Meier estimates of confirmed HIV RNA?≥50 copies/mL at W48 were 1.6% (n?=?2) in the 2DR and 3.1% (n?=?4) in the 3DR group. Development of treatment-emergent resistance was not observed.ConclusionsSwitching to DTG?+?bDRV was noninferior to continuing 3DR in subjects already treated with bDRV.