HIV-1–infected patients enrolled in switch studies may not be representative of switch patients in clinical practice due to strict inclusion/exclusion criteria. EMERALD allowed entry of patients with previous virologic failure (VF) or experience with multiple antiretrovirals (ARVs); we report Week 48 results by ARV treatment experience.
EMERALD was a phase 3, randomized (2:1), non-inferiority trial that evaluated the efficacy and safety of switching to the single-tablet regimen darunavir/cobicistat/emtricitabine/ tenofovir alafenamide (D/C/F/TAF; 800/150/200/10mg), or continuing use of a boosted protease inhibitor+F/tenofovir disoproxil fumarate (control), in virologically suppressed, HIV-1–infected adults. Patients had viral load (VL) <50 copies(c)/mL for ≥2 months (1 VL ≥50 and <200 c/mL allowed in 12 months before screening) and, if available, absence of historical darunavir resistance mutations. Those with previous non-darunavir VF and prior experience with multiple ARVs were allowed. The primary endpoint was proportion of patients with virologic rebound (confirmed VL ≥50 c/mL or premature discontinuation with last VL ≥50 c/mL) cumulative through Week 48. Secondary endpoints included virologic response and VF by FDA snapshot (50 c/mL threshold). Results were evaluated by prior VF and number of ARVs previously used.
In total, 1141 patients were randomized and treated; 14.8% (N=169) had prior VF, including 7.0% (N=80) of all patients with PI VF, 11.4% (N=130) with NRTI VF, and 6.5% (N=74) with NNRTI VF, and 27.3% (N=312) had used >7 ARVs. Overall rebound rates were 2.5% for D/C/F/TAF and 2.1% for control. Response rates were 94.9% and 93.7%, respectively. No resistance associated with any study drug was observed post-baseline. In patients with ≥1 prior VF, rebound rates were 2.6% for D/C/F/TAF and 0% for control (Table); response rates were 95.7% (D/C/F/TAF) and 92.5% (control), and VF rates were 1.7% and 0%, respectively. Overall, patients in the D/C/F/TAF and control arms had low and similar rates of discontinuation due to an adverse event (AE; 1.4% vs 1.3%), grade 3-4 AEs (6.8% vs 8.2%), and serious AEs (4.6% vs 4.8%). Virologic response rates were high and safety results were consistent across subgroups by ARV treatment experience.
Virologically suppressed, HIV-1–infected adults, including those with prior VF and experience with numerous ARVs, who switched to D/C/F/TAF had low cumulative virologic rebound and high virologic response rates over 48 weeks.