Background: Dolutegravir (DTG) and boosted darunavir (bDRV) are known as potent antiretroviral drugs with a high resistance barrier and well characterized drug-drug-interaction (DDI) profile.
Methods: DUALIS, a randomized, open-label, phase IIIb, non-inferiority clinical trial compared the switch to DTG+bDRV (2DR) versus continuation of therapy. PLWH with HIV-RNA < 50cps/mL on 2 NRTI+bDRV(3DR) for ≥24 weeks (one accepted blip < 200cps/mL) were randomized to switch to DTG 50mg+DRV 800mg (with 100mg Ritonavir or 150mg Cobicistat) or remain on 3DR. Primary endpoint (PE) was proportion of HIV-RNA < 50cps/mL at W48 (FDA snapshot, ITTe analysis set; change in NRTI-backbone was not classified as failure). Here we present a post-hoc subanalysis on PE, secondary endpoints and most frequent adverse events (AEs). Estimated sample size for analysis of PE was 292 (≤-10% non-inferiority margin).
Results: 263 subjects were randomized and treated (2DR n=131, 3DR n=132) after premature termination of recruitment due to slow recruitment; male 90.1%, Caucasian 89.7%, median age 48 years (IQR 39-54) and documented CDC stage C 29.7%. At W48, 86.3% (n=113/131) switching to 2DR and 87.9% (n=116/132) continuing on 3DR had HIV-RNA < 50cps/mL, difference -1.6% (95.48% confidence interval (CI, based on the adjusted alpha-level accounting for the interim analysis at week 24) -9.9-+6.7%). At W48 [W24], 90.1% (n=118/131) [92.4%; 121/131] switching to 2DR and 91.7% (n=121/132) [92.4%; 122/132] continuing on 3DR had HIV-RNA < 200cps/mL (difference -1.6% 95%CI -8.6-+5.4%; [-0.1%; -6.5-+6.3%]). Differences in PE within subgroups are shown in Table 1. The most frequent AEs (MedDRA SOC terms; in >10% of patients) were infections and infestations (2DR:49.6%, 3DR:50.4%), gastrointestinal (2DR:16.5%, 3DR:18.8%), musculosceletal (2DR:15.8%, 3DR:15.0%), skin (2DR:12.8%, 3DR:9.8%) and nervous system (2DR:9.0%, 3DR: 12.0%) disorders.

 NHIV-RNA <50cps/mL at W48 visit 2DR vs 3DRDifference (95% CI)
Male23787.0 vs 87.7%-0.7% (-9.2-+7.7%)
Female2681.3 vs 90.0%-8.8% (-35.4-+17.9%)
Age ≤50 ys16885.5 vs 88.2%-2.7% (-12.9-+7.5%)
Age >50 ys9587.5 vs 87.2%+0.3% (-13.1-+13.6%)
CDC A/B18587.5 vs 85.4%+2.1% (-7.8-+12.0%)
CDC C7882.9 vs 93.0%-10.2% (-24.8-+4.5%)
CD4 nadir ≥200 cells/µl11591.2 vs 87.9%+3.3% (-7.8-+14.4%)
CD4 nadir <200 cells/µl10286.0 vs 88.5%-2.5% (-15.4-+10.5%)
[Table 1: Differences in HIV-RNA <50cps/ml at week 48 by subgroups]

Conclusions: Switching to 2DR (DTG plus bDRV) was non-inferior to continuing 3DR with high rates of maintained viral suppression and comparable rates of AEs even in subgroups.

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