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Eron, Joseph J.; Orkin, Chloe; Cunningham, Douglas; Pulido, Federico; Post, Frank A.; De Wit, Stéphane; Lathouwers, Erkki; Jezorwski, John; Petrovic, Romana; Brown, Kimberley; Van Landuyt, Erika; Opsomer, Magda; De Wit, S.; Florence, E.; Van Wijngaerden, E.; Vandercam, B.; Brunetta, J.; Klein, M.; Murphy, D.; Rachlis, A.; Shafran, S.; Walmsley, S.; Ajana, F.; Cotte, L.; Girardy, P.-M.; Katlama, C.; Molina, J.-M.; Poizot-Martin, I.; Raffi, F.; Rey, D.; Reynes, J.; Teicher, E.; Yazdanpanah, Y.; Gasiorowski, J.; Piekarska, A.; Witor, A.; Arribas, J.R.; Perez-Valero, I.; Casado, J.; Gatell, J.M.; Gutierrez, F.; Galindo, M.J.; Gutierrez, M.D.M.; Iribarren, J.A.; Knobel, H.; Negredo, E.; Pineda, J.A.; Podzamczer, D.; Sogorb, J.Portilla; Pulido, F.; Ricart, C.; Rivero, A.; Santos Gil, I.; Blaxhult, A.; Flamholc, L.; Gisslèn, M.; Thalme, A.; Rauch, A.; Stoeckle, M.; Gazzard, B.G.; Post, F.; Ustianowski, A.; Bailey, J.; Benson, P.; Bhatti, L.; Brar, I.; Bredeek, U.F.; Brinson, C.; Dietz, C.; Dretler, R.; Felizarta, F.; Fichtenbaum, C.; Gallant, J.; Gathe, J.; Hagins, D.; Henn, S.; Henry, W.K.; Huhn, G.; Lucasti, C.; Martorell, C.; McDonald, C.; Mills, A.; Morales-Ramirez, J.; Mounzer, K.; Nahass, R.; Olivet, H.; Prelutsky, D.; Ramgopal, M.; Rashbaum, B.; Richmond, G.; Ruane, P.; Scarsella, A.; Scribner, A.; Shalit, P.; Shamblaw, D.; Slim, J.; Tashima, K.; Ward, D.; Wilkin, A.; de Vente, J.
Antiviral research, 10/2019, Letnik: 170Journal Article, Web Resource
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 ≥50 copies/mL) and VL < 50 copies/mL (virologic suppression) and ≥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 52–96). 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. •Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg is a once-daily, single-tablet regimen.•We present the week 96 analysis of D/C/F/TAF in the Phase 3 EMERALD trial in virologically suppressed HIV-1-positive adults.•Through 96 weeks, D/C/F/TAF had a low rebound rate (3%), high virologic suppression (>90%) with no resistance development.•Bone, renal and lipid safety were consistent with known D/C/F/TAF component profiles.•EMERALD week 96 results confirm the efficacy, high genetic barrier to resistance and safety benefits of D/C/F/TAF.
