@article{c09495bff94b49708c25105f0b9ff22c,
title = "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",
abstract = "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.",
keywords = "Darunavir/cobicistat/emtricitabine/TAF, Efficacy, Safety, Single-tablet regimen, Switch study",
author = "{EMERALD study group} and Eron, {Joseph J.} and C. Orkin and Douglas Cunningham and Federico Pulido and Post, {Frank A.} and {De Wit}, St{\'e}phane and E. Lathouwers and Veerle Hufkens and John Jezorwski and Romana Petrovic and Kimberley Brown and {Van Landuyt}, E. and M. Opsomer and {De Wit}, S. and E. Florence and M. Moutschen and {Van Wijngaerden}, E. and L. Vandekerckhove and B. Vandercam and J. Brunetta and B. Conway and M. Klein and D. Murphy and A. Rachlis and S. Shafran and S. Walmsley and F. Ajana and L. Cotte and Girardy, {P. M.} and C. Katlama and Molina, {J. M.} and I. Poizot-Martin and F. Raffi and D. Rey and J. Reynes and E. Teicher and Y. Yazdanpanah and J. Gasiorowski and W. Halota and A. Horban and A. Piekarska and A. Witor and Arribas, {J. R.} and I. Perez-Valero and J. Berenguer and J. Casado and Gatell, {J. M.} and F. Gutierrez and Galindo, {M. J.} and M. Jain",
note = "Funding Information: No patient developed resistance to any of the study drugs through week 96 despite a cumulative 1648 patient-years of exposure to D/C/F/TAF. This is consistent with previous DRV and D/C/F/TAF studies (Eron et al., 2018; Lathouwers et al., 2017), further supporting the high genetic barrier to resistance of DRV.J.J.E. has received research grants from Janssen, Gilead Sciences and ViiV Healthcare and has served as a consultant to BMS, Merck, Janssen, Gilead Sciences and ViiV Healthcare. C.O. has received speaker honoraria or consulting fees for attending speakers? bureaus or advisory boards and research grants from Janssen, Merck, ViiV Healthcare, and Gilead Sciences. D.C. has received research grants from Janssen, Merck, ViiV Healthcare and Gilead Sciences. F. Pulido has received speaker honoraria or consulting fees for attending advisory boards and research grants from Janssen, Merck, ViiV Healthcare, and Gilead Sciences. F. Post has received consulting fees from Gilead Sciences, Janssen, ViiV Healthcare and Merck and research grants from Gilead Sciences and ViiV Healthcare. S.D.W. has received consulting fees for attending advisory boards and research grants from Janssen, Merck, ViiV Healthcare and Gilead Sciences. E.L., V.H., K.B., and E.V.L. are all full-time employees of Janssen and potential stockholders of Johnson and Johnson. R.P. was a contractor for Janssen. We thank the patients and their families for their participation and support during the study, the central and local Janssen EMERALD study teams, study center staff, and the principal investigators. We also thank other Janssen staff members for their input into this manuscript. We also acknowledge Ian Woolveridge (Zoetic Science, an Ashfield company, Macclesfield, UK) for assistance in drafting the manuscript and coordinating and collating author contributions, which was funded by Janssen. The data sharing policy of Janssen Pharmaceutical Companies of Johnson & Johnson is available athttps://www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site athttp://yoda.yale.edu.",
year = "2019",
month = oct,
doi = "10.1016/j.antiviral.2019.104543",
language = "English (US)",
volume = "170",
journal = "Antiviral Research",
issn = "0166-3542",
publisher = "Elsevier",
}