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

Joseph J. Eron; Chloë M. Orkin; Douglas Cunningham; Federico Pulido; Frank A. Post; Stéphane De Wit; Erkki Lathouwers; Veerle Hufkens; John Jezorwski; Romana Petrovic; Kimberley Brown; Erika Van Landuyt; Magda Opsomer; Stéphane De Wit; Eric Florence; Michel P. Moutschen; Eric Van Wijngaerden; Linos Vandekerckhove; Bernard C. Vandercam; Jason M. Brunetta; Brian Conway; Marina Barbara Klein; Donald G. Murphy; Anita Rochelle Rachlis; Stephen D. Shafran; Sharon Walmsley; Faïza Ajana; Laurent Cotte; P. M. Girardy; Christine Katlama; Jean Michel Molina; Isabelle Poizot-Martin; François Raffi; David Rey; Jacques M. Reynes; Elina Teicher; Yazdan Yazdanpanah; Jacek Gasiorowski; Waldemar Halota; Andrzéj Horban; Anna M. Piekarska; Adam Witor; Jose Arribas; Ignacio Pérez Valero; Juan Berenguer; José Luis Casado; Jose Maria Gatell; Félix Gutiérrez; María José Galindo; Mª Del Mar Gutiérrez Macià; José Antonio Iribarren; Hernando Knobel Freud; Juan A. Pineda; Daniel Podzamczer; Joaquín Portilla Sogorb; F. Pulido; C. Ricart; Antonio Rivero Román; Ignacio de los Santos Gil; Anders Blaxhult; Leo Flamholc; Magnus Gisslèn; Anders Thalme; Jan Sven Fehr; Andri Rauch; Marcel P. Stoeckle; Amanda Clarke; B. G. Gazzard; Margaret A. Johnson; Chole Orkin; F. Post; Andrew P. Ustianowski; Laura Jane Waters; Justin R. Bailey; Paul Benson; Laveeza Bhatti; Indira Brar; Ulf Fritz Bredeek; Cynthia C. Brinson; Gordon E. Crofoot; Douglas Cunningham; Edwin DeJesus; Craig Allan Dietz; Robin Henry Dretler; J. Eron; Franco Antonio Felizarta; Carl Fichtenbaum; Joel E. Gallant; Joseph Clayton Gathe; Debbie P. Hagins; Sarah Henn; William Keith Henry; Gregory D. Huhn; Mamta K. Jain; Christopher J. Lucasti; Claudia T. Martorell; Cheryl Kay McDonald; Anthony Mills; Javier Osvaldo Morales-Ramirez; Karam C. Mounzer; Ronald G. Nahass; Hannah Olivet; Olayemi O. Osiyemi; David James Prelutsky; Moti N. Ramgopal; Bruce C. Rashbaum; Gary J. Richmond; Peter Jerome Ruane; Anthony John Scarsella; Anita R. Scribner; Peter Shalit; David J. Shamblaw; Jihad Slim; Karen T. Tashima; Gene W. Voskuhl; Douglas J. Ward; Aimee M. Wilkin; Jerome de Vente

doi:10.1016/j.antiviral.2019.104543

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

Joseph J. Eron, Chloë M. Orkin, Douglas Cunningham, Federico Pulido, Frank A. Post, Stéphane De Wit, Erkki Lathouwers, Veerle Hufkens, John Jezorwski, Romana Petrovic, Kimberley Brown, Erika Van Landuyt, Magda Opsomer, Stéphane De Wit, Eric Florence, Michel P. Moutschen, Eric Van Wijngaerden, Linos Vandekerckhove, Bernard C. Vandercam, Jason M. BrunettaBrian Conway, Marina Barbara Klein, Donald G. Murphy, Anita Rochelle Rachlis, Stephen D. Shafran, Sharon Walmsley, Faïza Ajana, Laurent Cotte, P. M. Girardy, Christine Katlama, Jean Michel Molina, Isabelle Poizot-Martin, François Raffi, David Rey, Jacques M. Reynes, Elina Teicher, Yazdan Yazdanpanah, Jacek Gasiorowski, Waldemar Halota, Andrzéj Horban, Anna M. Piekarska, Adam Witor, Jose Arribas, Ignacio Pérez Valero, Juan Berenguer, José Luis Casado, Jose Maria Gatell, Félix Gutiérrez, María José Galindo, Mª Del Mar Gutiérrez Macià, José Antonio Iribarren, Hernando Knobel Freud, Juan A. Pineda, Daniel Podzamczer, Joaquín Portilla Sogorb, F. Pulido, C. Ricart, Antonio Rivero Román, Ignacio de los Santos Gil, Anders Blaxhult, Leo Flamholc, Magnus Gisslèn, Anders Thalme, Jan Sven Fehr, Andri Rauch, Marcel P. Stoeckle, Amanda Clarke, B. G. Gazzard, Margaret A. Johnson, Chole Orkin, F. Post, Andrew P. Ustianowski, Laura Jane Waters, Justin R. Bailey, Paul Benson, Laveeza Bhatti, Indira Brar, Ulf Fritz Bredeek, Cynthia C. Brinson, Gordon E. Crofoot, Douglas Cunningham, Edwin DeJesus, Craig Allan Dietz, Robin Henry Dretler, J. Eron, Franco Antonio Felizarta, Carl Fichtenbaum, Joel E. Gallant, Joseph Clayton Gathe, Debbie P. Hagins, Sarah Henn, William Keith Henry, Gregory D. Huhn, Mamta K. Jain, Christopher J. Lucasti, Claudia T. Martorell, Cheryl Kay McDonald, Anthony Mills, Javier Osvaldo Morales-Ramirez, Karam C. Mounzer, Ronald G. Nahass, Hannah Olivet, Olayemi O. Osiyemi, David James Prelutsky, Moti N. Ramgopal, Bruce C. Rashbaum, Gary J. Richmond, Peter Jerome Ruane, Anthony John Scarsella, Anita R. Scribner, Peter Shalit, David J. Shamblaw, Jihad Slim, Karen T. Tashima, Gene W. Voskuhl, Douglas J. Ward, Aimee M. Wilkin, Jerome de Vente

Departament de Medicina

Producció científica: Contribució a revista › Article › Recerca › Avaluat per experts

35 Cites (Scopus)

Resum

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.

Idioma original	Anglès
Revista	Antiviral Research
Volum	170
DOIs	https://doi.org/10.1016/j.antiviral.2019.104543
Estat de la publicació	Publicada - 2019

SDG de les Nacions Unides

Aquest resultat contribueix als següents objectius de desenvolupament sostenible.

Accés al document

10.1016/j.antiviral.2019.104543

https://ddd.uab.cat/record/222892

Fingerprint

Navegar pels temes de recerca de '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'. Junts formen un fingerprint únic.

Com citar-ho

Eron, J. J., Orkin, C. M., Cunningham, D., Pulido, F., Post, F. A., De Wit, S., Lathouwers, E., Hufkens, V., Jezorwski, J., Petrovic, R., Brown, K., Van Landuyt, E., Opsomer, M., De Wit, S., Florence, E., Moutschen, M. P., Van Wijngaerden, E., Vandekerckhove, L., Vandercam, B. C., ... de Vente, J. (2019). 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. Antiviral Research, 170. https://doi.org/10.1016/j.antiviral.2019.104543

Eron, Joseph J. ; Orkin, Chloë M. ; Cunningham, Douglas et al. / 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. In: Antiviral Research. 2019 ; Vol. 170.

@article{1e9c7178282841678baea484ea95dae7,

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 = "Eron, {Joseph J.} and Orkin, {Chlo{\"e} M.} and Douglas Cunningham and Federico Pulido and Post, {Frank A.} and {De Wit}, St{\'e}phane and Erkki Lathouwers and Veerle Hufkens and John Jezorwski and Romana Petrovic and Kimberley Brown and {Van Landuyt}, Erika and Magda Opsomer and {De Wit}, St{\'e}phane and Eric Florence and Moutschen, {Michel P.} and {Van Wijngaerden}, Eric and Linos Vandekerckhove and Vandercam, {Bernard C.} and Brunetta, {Jason M.} and Brian Conway and Klein, {Marina Barbara} and Murphy, {Donald G.} and Rachlis, {Anita Rochelle} and Shafran, {Stephen D.} and Sharon Walmsley and Fa{\"i}za Ajana and Laurent Cotte and Girardy, {P. M.} and Christine Katlama and Molina, {Jean Michel} and Isabelle Poizot-Martin and Fran{\c c}ois Raffi and David Rey and Reynes, {Jacques M.} and Elina Teicher and Yazdan Yazdanpanah and Jacek Gasiorowski and Waldemar Halota and Andrz{\'e}j Horban and Piekarska, {Anna M.} and Adam Witor and Jose Arribas and {P{\'e}rez Valero}, Ignacio and Juan Berenguer and Casado, {Jos{\'e} Luis} and Gatell, {Jose Maria} and F{\'e}lix Guti{\'e}rrez and Galindo, {Mar{\'i}a Jos{\'e}} and {Guti{\'e}rrez Maci{\`a}}, {Mª Del Mar} and Iribarren, {Jos{\'e} Antonio} and {Knobel Freud}, Hernando and Pineda, {Juan A.} and Daniel Podzamczer and {Portilla Sogorb}, Joaqu{\'i}n and F. Pulido and C. Ricart and {Rivero Rom{\'a}n}, Antonio and {de los Santos Gil}, Ignacio and Anders Blaxhult and Leo Flamholc and Magnus Gissl{\`e}n and Anders Thalme and Fehr, {Jan Sven} and Andri Rauch and Stoeckle, {Marcel P.} and Amanda Clarke and Gazzard, {B. G.} and Johnson, {Margaret A.} and Chole Orkin and F. Post and Ustianowski, {Andrew P.} and Waters, {Laura Jane} and Bailey, {Justin R.} and Paul Benson and Laveeza Bhatti and Indira Brar and Bredeek, {Ulf Fritz} and Brinson, {Cynthia C.} and Crofoot, {Gordon E.} and Douglas Cunningham and Edwin DeJesus and Dietz, {Craig Allan} and Dretler, {Robin Henry} and J. Eron and Felizarta, {Franco Antonio} and Carl Fichtenbaum and Gallant, {Joel E.} and Gathe, {Joseph Clayton} and Hagins, {Debbie P.} and Sarah Henn and Henry, {William Keith} and Huhn, {Gregory D.} and Jain, {Mamta K.} and Lucasti, {Christopher J.} and Martorell, {Claudia T.} and McDonald, {Cheryl Kay} and Anthony Mills and Morales-Ramirez, {Javier Osvaldo} and Mounzer, {Karam C.} and Nahass, {Ronald G.} and Hannah Olivet and Osiyemi, {Olayemi O.} and Prelutsky, {David James} and Ramgopal, {Moti N.} and Rashbaum, {Bruce C.} and Richmond, {Gary J.} and Ruane, {Peter Jerome} and Scarsella, {Anthony John} and Scribner, {Anita R.} and Peter Shalit and Shamblaw, {David J.} and Jihad Slim and Tashima, {Karen T.} and Voskuhl, {Gene W.} and Ward, {Douglas J.} and Wilkin, {Aimee M.} and {de Vente}, Jerome",

year = "2019",

doi = "10.1016/j.antiviral.2019.104543",

language = "English",

volume = "170",

journal = "Antiviral Research",

issn = "0166-3542",

publisher = "Elsevier",

}

Eron, JJ, Orkin, CM, Cunningham, D, Pulido, F, Post, FA, De Wit, S, Lathouwers, E, Hufkens, V, Jezorwski, J, Petrovic, R, Brown, K, Van Landuyt, E, Opsomer, M, De Wit, S, Florence, E, Moutschen, MP, Van Wijngaerden, E, Vandekerckhove, L, Vandercam, BC, Brunetta, JM, Conway, B, Klein, MB, Murphy, DG, Rachlis, AR, Shafran, SD, Walmsley, S, Ajana, F, Cotte, L, Girardy, PM, Katlama, C, Molina, JM, Poizot-Martin, I, Raffi, F, Rey, D, Reynes, JM, Teicher, E, Yazdanpanah, Y, Gasiorowski, J, Halota, W, Horban, A, Piekarska, AM, Witor, A, Arribas, J, Pérez Valero, I, Berenguer, J, Casado, JL, Gatell, JM, Gutiérrez, F, Galindo, MJ, Gutiérrez Macià, MDM, Iribarren, JA, Knobel Freud, H, Pineda, JA, Podzamczer, D, Portilla Sogorb, J, Pulido, F, Ricart, C, Rivero Román, A, de los Santos Gil, I, Blaxhult, A, Flamholc, L, Gisslèn, M, Thalme, A, Fehr, JS, Rauch, A, Stoeckle, MP, Clarke, A, Gazzard, BG, Johnson, MA, Orkin, C, Post, F, Ustianowski, AP, Waters, LJ, Bailey, JR, Benson, P, Bhatti, L, Brar, I, Bredeek, UF, Brinson, CC, Crofoot, GE, Cunningham, D, DeJesus, E, Dietz, CA, Dretler, RH, Eron, J, Felizarta, FA, Fichtenbaum, C, Gallant, JE, Gathe, JC, Hagins, DP, Henn, S, Henry, WK, Huhn, GD, Jain, MK, Lucasti, CJ, Martorell, CT, McDonald, CK, Mills, A, Morales-Ramirez, JO, Mounzer, KC, Nahass, RG, Olivet, H, Osiyemi, OO, Prelutsky, DJ, Ramgopal, MN, Rashbaum, BC, Richmond, GJ, Ruane, PJ, Scarsella, AJ, Scribner, AR, Shalit, P, Shamblaw, DJ, Slim, J, Tashima, KT, Voskuhl, GW, Ward, DJ, Wilkin, AM & de Vente, J 2019, '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', Antiviral Research, vol. 170. https://doi.org/10.1016/j.antiviral.2019.104543

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. / Eron, Joseph J.; Orkin, Chloë M.; Cunningham, Douglas et al.
In: Antiviral Research, Vol. 170, 2019.

Producció científica: Contribució a revista › Article › Recerca › Avaluat per experts

TY - JOUR

T1 - 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

AU - Eron, Joseph J.

AU - Orkin, Chloë M.

AU - Cunningham, Douglas

AU - Pulido, Federico

AU - Post, Frank A.

AU - De Wit, Stéphane

AU - Lathouwers, Erkki

AU - Hufkens, Veerle

AU - Jezorwski, John

AU - Petrovic, Romana

AU - Brown, Kimberley

AU - Van Landuyt, Erika

AU - Opsomer, Magda

AU - De Wit, Stéphane

AU - Florence, Eric

AU - Moutschen, Michel P.

AU - Van Wijngaerden, Eric

AU - Vandekerckhove, Linos

AU - Vandercam, Bernard C.

AU - Brunetta, Jason M.

AU - Conway, Brian

AU - Klein, Marina Barbara

AU - Murphy, Donald G.

AU - Rachlis, Anita Rochelle

AU - Shafran, Stephen D.

AU - Walmsley, Sharon

AU - Ajana, Faïza

AU - Cotte, Laurent

AU - Girardy, P. M.

AU - Katlama, Christine

AU - Molina, Jean Michel

AU - Poizot-Martin, Isabelle

AU - Raffi, François

AU - Rey, David

AU - Reynes, Jacques M.

AU - Teicher, Elina

AU - Yazdanpanah, Yazdan

AU - Gasiorowski, Jacek

AU - Halota, Waldemar

AU - Horban, Andrzéj

AU - Piekarska, Anna M.

AU - Witor, Adam

AU - Arribas, Jose

AU - Pérez Valero, Ignacio

AU - Berenguer, Juan

AU - Casado, José Luis

AU - Gatell, Jose Maria

AU - Gutiérrez, Félix

AU - Galindo, María José

AU - Gutiérrez Macià, Mª Del Mar

AU - Iribarren, José Antonio

AU - Knobel Freud, Hernando

AU - Pineda, Juan A.

AU - Podzamczer, Daniel

AU - Portilla Sogorb, Joaquín

AU - Pulido, F.

AU - Ricart, C.

AU - Rivero Román, Antonio

AU - de los Santos Gil, Ignacio

AU - Blaxhult, Anders

AU - Flamholc, Leo

AU - Gisslèn, Magnus

AU - Thalme, Anders

AU - Fehr, Jan Sven

AU - Rauch, Andri

AU - Stoeckle, Marcel P.

AU - Clarke, Amanda

AU - Gazzard, B. G.

AU - Johnson, Margaret A.

AU - Orkin, Chole

AU - Post, F.

AU - Ustianowski, Andrew P.

AU - Waters, Laura Jane

AU - Bailey, Justin R.

AU - Benson, Paul

AU - Bhatti, Laveeza

AU - Brar, Indira

AU - Bredeek, Ulf Fritz

AU - Brinson, Cynthia C.

AU - Crofoot, Gordon E.

AU - Cunningham, Douglas

AU - DeJesus, Edwin

AU - Dietz, Craig Allan

AU - Dretler, Robin Henry

AU - Eron, J.

AU - Felizarta, Franco Antonio

AU - Fichtenbaum, Carl

AU - Gallant, Joel E.

AU - Gathe, Joseph Clayton

AU - Hagins, Debbie P.

AU - Henn, Sarah

AU - Henry, William Keith

AU - Huhn, Gregory D.

AU - Jain, Mamta K.

AU - Lucasti, Christopher J.

AU - Martorell, Claudia T.

AU - McDonald, Cheryl Kay

AU - Mills, Anthony

AU - Morales-Ramirez, Javier Osvaldo

AU - Mounzer, Karam C.

AU - Nahass, Ronald G.

AU - Olivet, Hannah

AU - Osiyemi, Olayemi O.

AU - Prelutsky, David James

AU - Ramgopal, Moti N.

AU - Rashbaum, Bruce C.

AU - Richmond, Gary J.

AU - Ruane, Peter Jerome

AU - Scarsella, Anthony John

AU - Scribner, Anita R.

AU - Shalit, Peter

AU - Shamblaw, David J.

AU - Slim, Jihad

AU - Tashima, Karen T.

AU - Voskuhl, Gene W.

AU - Ward, Douglas J.

AU - Wilkin, Aimee M.

AU - de Vente, Jerome

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - Darunavir/cobicistat/emtricitabine/TAF

KW - Efficacy

KW - Safety

KW - Single-tablet regimen

KW - Switch study

U2 - 10.1016/j.antiviral.2019.104543

DO - 10.1016/j.antiviral.2019.104543

M3 - Article

C2 - 31279073

SN - 0166-3542

VL - 170

JO - Antiviral Research

JF - Antiviral Research

ER -

Eron JJ, Orkin CM, Cunningham D, Pulido F, Post FA, De Wit S et al. 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. Antiviral Research. 2019;170. doi: 10.1016/j.antiviral.2019.104543