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
Christoph D. Spinner, Tim Kümmerle, Jochen Schneider, Christiane Cordes, Hans Heiken, Hans‐Jürgen Stellbrink, Ivanka Krznaric, Stephan Scholten, Björn‐Erik Ole Jensen, Christoph Wyen, Marin Viehweger, Clara Lehmann, Martin F. Sprinzl, Albrecht Stoehr, Markus Bickel, Heiko Jessen, Wilfried Obst, Petra Spornraft‐Ragaller, Pavel Khaykin, Eva Wolf, Christoph Boesecke, DUALIS Study Group, Christoph D. Spinner, Björn Jensen, Thomas A. Lutz, Petra Spornraft‐Ragaller, Stellbrink, Martin Hower, Ulrich Bohr, Wilfried Obst, Ivanka Krznaric, Martin Sprinzl, Franz Audebert, Tim Kuemmerle, Stefan Scholten, Heribert Hillenbrand, Christiane Cordes, Heribert Knechten, Birger Kuhlmann, Heiko Jessen, P. Beck, Gerd Fätkenheuer, Hartwig Klinker, Juergen Rockstroh, Stefan Esser, Christoph Stephan, Olaf Degen, Andreas Bellmunt-Zschäpe, Pavel Khaykin, Norbert H. Brockmeyer, Albrecht Stoehr
Abstract
BACKGROUND: Dolutegravir (DTG) and boosted darunavir (bDRV) are potent antiretrovirals with a high resistance barrier and might be valuable switch options for people with HIV (PWH). METHODS: DUALIS, 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%. RESULTS: In 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. CONCLUSIONS: Switching to DTG + bDRV was noninferior to continuing 3DR in subjects already treated with bDRV.