Week 96 efficacy and safety results of the phase 3, randomized EMERALD trial to evaluate switching from boosted-protease inhibitors plus emtricitabine/tenofovir disoproxil fumarate regimens to the once daily, single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in treatment-experienced, virologically-suppressed adults living with HIV-1
Creators: name: Bailey, J.
name: Ajana, F.
name: Arribas, J.R.
name: Brunetta, J.
name: Halota, W.
name: Raffi, F.
name: Brinson, C.
name: Eron, J.
name: Post, F.
name: Ward, D.
name: Katlama, C.
name: Pineda, J.A.
name: Rauch, A.
name: Vandercam, B.
name: Molina, J.-M.
name: Slim, J.
name: Crofoot, G.
name: Prelutsky, D.
name: Shamblaw, D.
name: Van Wijngaerden, E.
name: Opsomer, M.
name: Pulido, F.
name: Brown, K.
name: Henn, S.
name: Santos Gil, I.
name:  Perez-Valero, I.
name: Flamholc, L.
name: Ruane, P.
name: Ricart, C.
name: De Wit, S.
name: Rey, D.
name: Post, F.A.
name: Murphy, D.
name: Negredo, E.
name: Gatell, J.M.
name: Gathe, J.
name: DeJesus, E.
name: Iribarren, J.A.
name: Rashbaum, B.
name: De Wit, S.
name: Fehr, J.
name: Dretler, R.
name: Brar, I.
name: Hagins, D.
name: Voskuhl, G.
name: Jain, M.
name: Henry, W.K.
name: Gasiorowski, J.
name: Mills, A.
name: Rivero, A.
name: Van Landuyt, E.
name: Gutierrez, F.
name: Petrovic, R.
name: Gazzard, B.G.
name: Piekarska, A.
name: Walmsley, S.
name: de Vente, J.
name: Girardy, P.-M.
name: Shafran, S.
name: Rachlis, A.
name: Bhatti, L.
name: Knobel, H.
name: Sogorb, J.P.
name: Cunningham, D.
name: Mounzer, K.
name: Klein, M.
name: Galindo, M.J.
name: Clarke, A.
name: Stoeckle, M.
name: Fichtenbaum, C.
name: Dietz, C.
name: EMERALD study group
name: Olivet, H.
name: Poizot-Martin, I.
name: Nahass, R.
name: Richmond, G.
name: Eron, J.J.
name: Wilkin, A.
name: Pulido, F.
name: Benson, P.
name: Morales-Ramirez, J.
name: Lathouwers, E.
name: Lucasti, C.
name: Moutschen, M.
name: Osiyemi, O.
name: Cunningham, D.
name: Casado, J.
name: Gallant, J.
name: Jezorwski, J.
name: Teicher, E.
name: Cotte, L.
name: Vandekerckhove, L.
name: Podzamczer, D.
name: Gisslen, M.
name: Gutierrez, M.D.M.
name: Bredeek, U.F.
name: Waters, L.
name: Scribner, A.
name: Orkin, C.
name: Conway, B.
name: Yazdanpanah, Y.
name: Felizarta, F.
name: Reynes, J.
name: Johnson, M.A.
name: Ustianowski, A.
name: Thalme, A.
name: Martorell, C.
name: Orkin, C.
name: McDonald, C.
name: Tashima, K.
name: Berenguer, J.
name: Florence, E.
name: Huhn, G.
name: Shalit, P.
name: Ramgopal, M.
name: Witor, A.
name: Blaxhult, A.
name: Scarsella, A.
name: Horban, A.
name: Hufkens, V.
Publisher: name: Elsevier B.V.
Year: 2019

description: Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in EMERALD (NCT02269917). Virologically-suppressed, HIV-1-positive treatment-experienced adults (previous non-darunavir virologic failure [VF] allowed) were randomized (2:1) to D/C/F/TAF or boosted protease inhibitor (PI) plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) over 48 weeks. At week 52 participants in the boosted PI arm were offered switch to D/C/F/TAF (late-switch, 44 weeks D/C/F/TAF exposure). All participants were followed on D/C/F/TAF until week 96. Efficacy endpoints were percentage cumulative protocol-defined virologic rebound (PDVR; confirmed viral load [VL] Ã¢â€°Â¥50 copies/mL) and VL < 50 copies/mL (virologic suppression) and Ã¢â€°Â¥50 copies/mL (VF) (FDA-snapshot analysis). Of 1141 randomized patients, 1080 continued in the extension phase. Few patients had PDVR (D/C/F/TAF: 3.1%, 24/763 cumulative through week 96; late-switch: 2.3%, 8/352 week 52Ã¢â‚¬â€œ96). Week 96 virologic suppression was 90.7% (692/763) (D/C/F/TAF) and 93.8% (330/352) (late-switch). VF was 1.2% and 1.7%, respectively. No darunavir, primary PI, tenofovir or emtricitabine resistance-associated mutations were observed post-baseline. No patients discontinued for efficacy-related reasons. Few discontinued due to adverse events (2% D/C/F/TAF arm). Improved renal and bone parameters were maintained in the D/C/F/TAF arm and observed in the late-switch arm, with small increases in total cholesterol/high-density-lipoprotein-cholesterol ratio. A study limitation was the lack of a control arm in the week 96 analysis. Through 96 weeks, D/C/F/TAF resulted in low PDVR rates, high virologic suppression rates, very few VFs, and no resistance development. Late-switch results were consistent with D/C/F/TAF week 48 results. EMERALD week 96 results confirm the efficacy, high genetic barrier to resistance and safety benefits of D/C/F/TAF.