Search

Your search keyword '"darunavir/cobicistat/emtricitabine/TAF"' showing total 6 results
Start Over Descriptor "darunavir/cobicistat/emtricitabine/TAF"
6 results on '"darunavir/cobicistat/emtricitabine/TAF"'

1. Week 96 resistance analyses of the once‐daily, single‐tablet regimen (STR) darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in adults living with HIV‐1 from the phase 3 randomized AMBER and EMERALD trials.

Author

Lathouwers, Erkki, Weinsteiger, Shirley, Baugh, Bryan, Ghys, Anne, Jezorwski, John, Mohsine, El Ghazi, Van Landuyt, Erika, and De Meyer, Sandra

Subjects
DARUNAVIR, TENOFOVIR, EMTRICITABINE, HIV, EMERALDS
Abstract

In AMBER and EMERALD, darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg demonstrated high virological response and low virological failure (VF) through week 96. Week 96 resistance analyses are presented. Post‐baseline samples for genotyping/phenotyping were analyzed from protocol‐defined‐VFs with viral load (VL) ≥ 400 copies/ml at failure/later time points. Post‐hoc analyses were deep sequencing (AMBER) and HIV‐1 proviral DNA sequencing from baseline samples (VL < 50 copies/ml) (EMERALD). Through week 96 across studies, no darunavir, primary protease inhibitor (PI), or tenofovir resistance‐associated‐mutations (RAMs) occurred in patients continuing (N = 1125) or switching to D/C/F/TAF (N = 715). M184I/V (emtricitabine RAM) was detected in one patient in each arm of AMBER. In EMERALD D/C/F/TAF patients with prior VF and baseline genoarchive data (N = 98), 4% had darunavir RAMs, 36% emtricitabine RAMs, mainly at position 184 (32%), 4% tenofovir RAMs, and 19% ≥3 thymidine‐analogue‐associated‐mutations at screening. The predicted phenotype showed 0% had reduced susceptibility to darunavir, 37% to emtricitabine, and 22% to tenofovir. All achieved VL < 50 copies/ml at week 96/prior discontinuation, with no VF. D/C/F/TAF has a high barrier to resistance; no darunavir, primary PI, or tenofovir RAMs occurred through 96 weeks in AMBER and EMERALD. In EMERALD, baseline archived darunavir, emtricitabine, and tenofovir RAMs in patients with prior VF did not preclude virologic response. Highlights: In the Phase 3 AMBER (treatment‐naïve patients) and EMERALD (virologically suppressed treatment‐experienced patients) studies through week 96, almost no resistance mutations related to the study drugs were observed: no darunavir, primary protease inhibitor or tenofovir resistance‐associated‐mutations (RAMs) occurred post‐baseline in 1125 patients continuing on the once‐daily, single‐tablet regimen (STR), darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg or in 715 patients switching to D/C/F/TAF. The emtricitabine RAM, M184I/V, was detected in only one patient in each arm of AMBER.In EMERALD in the patients with prior virologic failure and baseline genoarchive data who received D/C/F/TAF, baseline archived darunavir, emtricitabine, and tenofovir RAMs, including those with predicted antiretroviral resistance, did not preclude virologic response.The D/C/F/TAF once‐daily STR provides a convenient treatment option, combining the efficacy and high barrier to resistance of darunavir with the safety advantages of TAF for treatment‐naïve and ‐experienced adults living with HIV‐1. [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

2. Week 48 Resistance Analyses of the Once-Daily, Single-Tablet Regimen Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) in Adults Living with HIV-1 from the Phase III Randomized AMBER and EMERALD Trials.

Abstract

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg is being investigated in two Phase III trials, AMBER (NCT02431247; treatment-naive adults) and EMERALD (NCT02269917; treatment-experienced, virologically suppressed adults). Week 48 AMBER and EMERALD resistance analyses are presented. Postbaseline samples for genotyping/phenotyping were analyzed from protocol-defined virologic failures (PDVFs) with viral load (VL) ≥400 copies/mL at failure/later time points. Post hoc analyses were deep sequencing in AMBER, and HIV-1 proviral DNA from baseline samples (VL <50 copies/mL) in EMERALD. Through week 48 across both studies, no darunavir, primary PI, or tenofovir resistance-associated mutations (RAMs) were observed in HIV-1 viruses of 1,125 participants receiving D/C/F/TAF or 629 receiving boosted darunavir plus emtricitabine/tenofovir-disoproxil-fumarate. In AMBER, the nucleos(t)ide analog reverse transcriptase inhibitor (N(t)RTI) RAM M184I/V was identified in HIV-1 of one participant during D/C/F/TAF treatment. M184V was detected pretreatment as a minority variant (9%). In EMERALD, in participants with prior VF and genoarchive data (N = 140; 98 D/C/F/TAF and 42 control), 4% had viruses with darunavir RAMs, 38% with emtricitabine RAMs, mainly at position 184 (41% not fully susceptible to emtricitabine), 4% with tenofovir RAMs, and 21% ≥ 3 thymidine analog-associated mutations (24% not fully susceptible to tenofovir) detected at screening. All achieved VL <50 copies/mL at week 48 or prior discontinuation. D/C/F/TAF has a high genetic barrier to resistance; no darunavir, primary PI, or tenofovir RAMs were observed through 48 weeks in AMBER and EMERALD. Only one postbaseline M184I/V RAM was observed in HIV-1 of an AMBER participant. In EMERALD, baseline archived RAMs to darunavir, emtricitabine, and tenofovir in participants with prior VF did not preclude virologic response. [ABSTRACT FROM AUTHOR]

Published
2020
Full Text
View/download PDF

3. 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

Author

Douglas Cunningham, D. Ward, Mamta K. Jain, Faiza Ajana, Magda Opsomer, Anita Rachlis, Sharon Walmsley, Frank A. Post, Anders Blaxhult, Amanda Clarke, M. J. Galindo, Marcel Stoeckle, P.-M. Girardy, Karam Mounzer, David Shamblaw, U. F. Bredeek, L. Bhatti, J. J. Eron, Andrew Ustianowski, Mar Gutierrez, John Jezorwski, Javier O Morales-Ramirez, Antonio Rivero, M.A. Johnson, Gatell Jm, Erika Van Landuyt, Stéphane De Wit, A. Wilkin, Laurent Cotte, Cheryl McDonald, D. Murphy, Cynthia Brinson, Romana Petrovic, Olayemi Osiyemi, J. de Vente, I. Poizot-Martin, Juan Berenguer, Robin Dretler, J. Bailey, B. Rashbaum, Moti Ramgopal, A. Scribner, Yazdan Yazdanpanah, Eric Florence, A. Piekarska, Brian Gazzard, Chloe Orkin, W. Halota, Gary Richmond, Jacques Reynes, C. Ricart, C. Lucasti, Ignacio Pérez-Valero, Jason Brunetta, S. Shafran, Daniel Podzamczer, Franco Antonio Felizarta, Claudia Martorell, F. Post, Peter Ruane, Edwin DeJesus, J. Portilla Sogorb, C. Orkin, K. Tashima, Federico Pulido, Bernard Vandercam, F. Pulido, José L. Casado, Christine Katlama, Kimberley Brown, J Gasiorowski, A. Witor, Joseph J. Eron, Brian Conway, Andri Rauch, Jose R. Arribas, Michel Moutschen, H. Olivet, A. Scarsella, Leo Flamholc, A. Horban, D. Cunningham, Ronald Nahass, Félix Gutiérrez, G. Huhn, W.K. Henry, A. Thalme, S De Wit, Jan Fehr, Debbie Hagins, José Antonio Iribarren, J.-M. Molina, S. Henn, F Raffi, Juan A. Pineda, Marina B. Klein, Eugenia Negredo, Hernando Knobel, J. Slim, P. Benson, L. Waters, E. Teicher, Linos Vandekerckhove, Craig A. Dietz, Magnus Gisslén, Joel E. Gallant, J. Gathe, P. Shalit, D. Prelutsky, G. Voskuhl, D. Rey, E. Van Wijngaerden, Anthony Mills, Erkki Lathouwers, Carl J. Fichtenbaum, I. Brar, Gordon Crofoot, Veerle Hufkens, I. Santos Gil, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Queen Mary University of London (QMUL), Pueblo Family Physicians, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), King's College Hospital (KCH), Université libre de Bruxelles (ULB), Janssen Pharmaceutica [Beerse], Janssen Research & Development, Institute of Tropical Medicine [Antwerp] (ITM), Department of Infectious and Parasitic Diseases (University Liege), Université de Liège, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Living Hope Foundation, Ghent University Hospital, Cliniques Universitaires Saint-Luc [Bruxelles], Maple Leaf Clinic, Vancouver Infectious Diseases Centre, McGill University = Université McGill [Montréal, Canada], University of Toronto, Sunnybrook Health Sciences Centre, University of Alberta, University Health Network, Services des maladies infectieuses [Tourcoing], Centre Hospitalier de Tourcoing, Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de maladies infectieuses et tropicales [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Strasbourg, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Maladies Infectieuses et Tropicales [CHU Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Wrocław [Poland] (UWr), Faculty of Medicine [Bydgoszcz, Poland], Nicolaus Copernicus University [Toruń], Medical University of Warsaw - Poland, Medical University of Łódź (MUL), Regional Hospital [Chorzow, Poland], La Paz Hospital, IdiPAZ, Hospital General Universitario 'Gregorio Marañón' [Madrid], Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), Infectious Diseases Service, AIDS Research Group, Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Barcelona, Spain., Hospital Universitario de Elche, Hospital Universitario de Valencia, Hospital de la Santa Creu i Sant Pau, Donostia Hospital Universitario San Sebastian, IMIM-Hospital del Mar, Generalitat de Catalunya, LLuita contra la Sida Fdn-HIV Unit, Germans Trias i Pujol University Hospital- Universitat Autònoma de Barcelona, Hospital Universitario de Valme, Hospital Universitari de Bellvitge, Universitat de València (UV), Hospital Universitario Reina Sofía, Hospital La Princesa, Madrid, Karolinska Institutet, Södersjukhuset, Skane University Hospital [Malmo], Lund University [Lund], University of Gothenburg (GU), Karolinska University Hospital [Stockholm], University hospital of Zurich [Zurich], Bern University Hospital [Berne] (Inselspital), University Hospital Basel [Basel], Royal Sussex County Hospital, Chelsea and Westminster Hospital, North Manchester General Hospital, University College of London [London] (UCL), Johns Hopkins University School of Medicine [Baltimore], Be Well, AIDS healthcare foundation [California], Henry Ford Hospital, Metropolis Medical, Central Texas Clinical Research, The Crofoot Research Center, Orlando Immunology Center, Kansas City Free Health Clinic, University of Cincinnati (UC), University of Minnesota System, University of Texas Southwestern Medical Center, South Jersey Infectious Disease, Infectious Disease, Tarrant County Infectious Disease Associates, Southern California Men’s Medical Group, Clinical Research Puerto Rico Inc, Philadelphia FIGHT, ID care, Community Research Initiative of New England, Triple O Research Institute PA, Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Midway Immunology Center, Capital Medical Associates, Broward General Medical Center, Ruane Clinical Research Group, Pacific Oaks Medical Group, DCOL Center for Clinical Research, Peter Shalit MD and Associates, La Playa Medical Group, Seton Hall University, Warren Alpert Medical School of Brown University, AIDS Arms, Inc, Dupont Circle Physicians Group, Wake Forest School of Medicine [Winston-Salem], Wake Forest Baptist Medical Center, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Hospital Universitario Donostia [San Sebastian, Spain] (HUD), Universitat Autònoma de Barcelona (UAB), Hospital Universitario de La Princesa, HAL AMU, Administrateur, UCL - SSS/IREC/SLUC - Pôle St.-Luc, and UCL - (SLuc) Service de médecine interne générale

Subjects
Male, DOLUTEGRAVIR, Sustained Virologic Response, HIV Infections, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Medicine and Health Sciences, Emtricitabine, 030212 general & internal medicine, Pharmacology & Pharmacy, Darunavir, 0303 health sciences, Alanine, Drug Substitution, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination, Lamivudine, Antiretrovirals, Middle Aged, Viral Load, OPEN-LABEL, 3. Good health, WEIGHT-GAIN, Drug Combinations, Treatment Outcome, Dolutegravir, NON-INFERIORITY, Female, Safety, Viral load, Life Sciences & Biomedicine, medicine.drug, Tablets, Adult, medicine.medical_specialty, Efficacy, Anti-HIV Agents, RITONAVIR, TENOFOVIR ALAFENAMIDE, LAMIVUDINE, Tenofovir alafenamide, Single-tablet regimen, 03 medical and health sciences, Internal medicine, Virology, medicine, VIH (Virus), Humans, Switch study, Protease Inhibitors, Tenofovir, Aged, Pharmacology, Science & Technology, 030306 microbiology, business.industry, HIV (Viruses), Adenine, Darunavir/cobicistat/emtricitabine/TAF, Antiretroviral agents, COBICISTAT, MAINTENANCE, chemistry, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, HIV-1, Ritonavir, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, RESISTANCE
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

Published
2019
Full Text
View/download PDF

4. Week 48 Resistance Analyses of the Once-Daily, Single-Tablet Regimen Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) in Adults Living with HIV-1 from the Phase III Randomized AMBER and EMERALD Trials

Author

Lathouwers, Erkki, Wong, Eric Y, Brown, Kimberley, Baugh, Bryan, Ghys, Anne, Jezorwski, John, Mohsine, El Ghazi, Van Landuyt, Erika, Opsomer, Magda, De Meyer, Sandra, De Wit, S, Florence, E, Vandekerckhove, L, Vandercam, B, Brunetta, J, Klein, M, Murphy, D, Rachlis, A, Walmsley, S, Ajana, F, Cotte, L, Girard, P-M, Katlama, C, Molina, J-M, Poizot-Martin, I, Raffi, F, Rey, D, Reynes, J, Teicher, E, Yazdanpanah, Y, Arasteh, K, Bickel, M, Bogner, J, Esser, S, Faetkenheuer, G, Jessen, H, Kern, W, Rockstroh, J, Spinner, C, Stellbrink, H-J, Stoehr, A, Antinori, A, Castelli, F, Chirianni, A, De Luca, A, Di Biagio, A, Galli, M, Lazzarin, A, Maggiolo, F, Maserati, R, Mussini, C, Garlicki, A, Gasiorowski, J, Halota, W, Horban, A, Parczewski, M, Piekarska, A, Belonosova, E, Chernova, O, Dushkina, N, Kulagin, V, Ryamova, E, Shuldyakov, A, Sizova, N, Tsybakova, O, Voronin, E, Yakovlev, A, Antela, A, Arribas, JR, Berenguer, J, Casado, J, Estrada, V, Galindo, MJ, Garcia Del Toro, M, Gatell, JM, Gorgolas, M, Gutierrez, F, Gutierrez, MDM, Negredo, E, Pineda, JA, Podzamczer, D, Portilla Sogorb, J, Rivero, A, Rubio, R, Viciana, P, De Los Santos, I, Clarke, A, Gazzard, BG, Johnson, MA, Orkin, C, Reeves, I, Waters, L, Benson, P, Bhatti, L, Bredeek, F, Crofoot, G, Cunningham, D, DeJesus, E, Eron, J, Felizarta, F, Franco, R, Gallant, J, Hagins, D, Henry, K, Jayaweera, D, Lucasti, C, Martorell, C, McDonald, C, McGowan, J, Mills, A, Morales-Ramirez, J, Prelutsky, D, Ramgopal, M, Rashbaum, B, Ruane, P, Slim, J, Wilkin, A, deVente, J, Moutschen, M, Van Wijngaerden, E, Vekerckhove, L, Vercam, B, Conway, B, Shafran, S, Janssen Pharmaceutica [Beerse], Janssen Pharmaceutical Research and Development Titusville, AMBER and EMERALD Study Groups: S De Wit, E Florence, L Vandekerckhove, B Vandercam, J Brunetta, M Klein, D Murphy, A Rachlis, S Walmsley, F Ajana, L Cotte, P-M Girard, C Katlama, J-M Molina, I Poizot-Martin, F Raffi, D Rey, J Reynes, E Teicher, Y Yazdanpanah, K Arastéh, M Bickel, J Bogner, S Esser, G Faetkenheuer, H Jessen, W Kern, J Rockstroh, C Spinner, H-J Stellbrink, A Stoehr, A Antinori, F Castelli, A Chirianni, A De Luca, A Di Biagio, M Galli, A Lazzarin, F Maggiolo, R Maserati, C Mussini, A Garlicki, J Gasiorowski, W Halota, A Horban, M Parczewski, A Piekarska, E Belonosova, O Chernova, N Dushkina, V Kulagin, E Ryamova, A Shuldyakov, N Sizova, O Tsybakova, E Voronin, A Yakovlev, A Antela, J R Arribas, J Berenguer, J Casado, V Estrada, M J Galindo, M Garcia Del Toro, J M Gatell, M Gorgolas, F Gutierrez, Mdm Gutierrez, E Negredo, J A Pineda, D Podzamczer, J Portilla Sogorb, A Rivero, R Rubio, P Viciana, I De Los Santos, A Clarke, B G Gazzard, M A Johnson, C Orkin, I Reeves, L Waters, P Benson, L Bhatti, F Bredeek, G Crofoot, D Cunningham, E DeJesus, J Eron, F Felizarta, R Franco, J Gallant, D Hagins, K Henry, D Jayaweera, C Lucasti, C Martorell, C McDonald, J McGowan, A Mills, J Morales-Ramirez, D Prelutsky, M Ramgopal, B Rashbaum, P Ruane, J Slim, A Wilkin, J deVente, S De Wit, E Florence, M Moutschen, E Van Wijngaerden, L Vandekerckhove, B Vandercam, J Brunetta, B Conway, M Klein, D Murphy, A Rachlis, S Shafran, S Walmsley, F Ajana, L Cotte, P-M Girard, C Katlama, J-M Molina, I Poizot-Martin, F Raffi, D Rey, J Reynes, E Teicher, Y Yazdanpanah, J Gasiorowski, W Halota, A Horban, A Piekarska, A Witor, J R Arribas, I Perez-Valero, J Berenguer, J Casado, J M Gatell, F Gutierrez, M J Galindo, Mdm Gutierrez, J A Iribarren, H Knobel, E Negredo, J A Pineda, D Podzamczer, J Portilla Sogorb, F Pulido, C Ricart, A Rivero, I Santos Gil, A Blaxhult, L Flamholc, M Gisslèn, A Thalme, J Fehr, A Rauch, M Stoeckle, A Clarke, B G Gazzard, M A Johnson, C Orkin, F Post, A Ustianowski, L Waters, J Bailey, P Benson, L Bhatti, I Brar, U F Bredeek, C Brinson, G Crofoot, D Cunningham, E DeJesus, C Dietz, R Dretler, J Eron, F Felizarta, C Fichtenbaum, J Gallant, J Gathe, D Hagins, S Henn, K W Henry, G Huhn, M Jain, C Lucasti, C Martorell, C McDonald, A Mills, J Morales-Ramirez, K Mounzer, R Nahass, H Olivet, O Osiyemi, D Prelutsky, M Ramgopal, B Rashbaum, G Richmond, P Ruane, A Scarsella, A Scribner, P Shalit, D Shamblaw, J Slim, K Tashima, G Voskuhl, D Ward, A Wilkin, J de Vente, and Malbec, Odile

Subjects
0301 basic medicine, [SDV]Life Sciences [q-bio], efficacy, Human immunodeficiency virus (HIV), HIV Infections, darunavir, medicine.disease_cause, VIRALLY SUPPRESSED ADULTS, PLUS LAMIVUDINE, DOUBLE-BLIND, 0302 clinical medicine, INFECTION, Medicine and Health Sciences, Emtricitabine, 030212 general & internal medicine, Darunavir, Emtricitabine tenofovir alafenamide, Alanine, Cobicistat, Single tablet regimen, virus diseases, Viral Load, OPEN-LABEL, 3. Good health, [SDV] Life Sciences [q-bio], Drug Combinations, Infectious Diseases, NON-INFERIORITY, INITIAL TREATMENT, Reverse Transcriptase Inhibitors, Life Sciences & Biomedicine, Tablets, medicine.drug, Adult, TENOFOVIR DISOPROXIL FUMARATE, Anti-HIV Agents, Darunavir/Cobicistat, Immunology, archived RAMs, Tenofovir alafenamide, Drug Administration Schedule, single-tablet regimen, resistance, 03 medical and health sciences, deep sequencing, Virology, Drug Resistance, Viral, medicine, darunavir/cobicistat/emtricitabine/TAF, Humans, Clinical Trials/Clinical Studies, Tenofovir, emtricitabine, DRUG-RESISTANCE, Science & Technology, TREATMENT-NAIVE PATIENTS, business.industry, Adenine, cobicistat, 030104 developmental biology, TAF, HIV-1, business
Abstract

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg is being investigated in two Phase III trials, AMBER (NCT02431247; treatment-naive adults) and EMERALD (NCT02269917; treatment-experienced, virologically suppressed adults). Week 48 AMBER and EMERALD resistance analyses are presented. Postbaseline samples for genotyping/phenotyping were analyzed from protocol-defined virologic failures (PDVFs) with viral load (VL) ≥400 copies/mL at failure/later time points. Post hoc analyses were deep sequencing in AMBER, and HIV-1 proviral DNA from baseline samples (VL

Published
2019
Full Text
View/download PDF

5. 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

Author

Eron, Joseph J., Orkin, Chloe, Cunningham, Douglas, Pulido, Federico, Post, Frank A., De Wit, Stéphane, Lathouwers, Erkki, Hufkens, Veerle, Jezorwski, John, Petrovic, Romana, Brown, Kimberley, Van Landuyt, Erika, and Opsomer, Magda

Subjects
*ADULTS, *VIRAL load, *PROTEASE inhibitors, *RIBAVIRIN, *ADVERSE health care events
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. • 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. [ABSTRACT FROM AUTHOR]

Published
2019
Full Text
View/download PDF

6. Week 48 Resistance Analyses of the Once-Daily, Single-Tablet Regimen Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) in Adults Living with HIV-1 from the Phase III Randomized AMBER and EMERALD Trials.

Author

Lathouwers E, Wong EY, Brown K, Baugh B, Ghys A, Jezorwski J, Mohsine EG, Van Landuyt E, Opsomer M, and De Meyer S

Subjects
Adenine administration & dosage, Adult, Alanine, Anti-HIV Agents administration & dosage, Drug Administration Schedule, Drug Combinations, HIV Infections epidemiology, HIV-1 drug effects, Humans, Reverse Transcriptase Inhibitors administration & dosage, Tablets administration & dosage, Tenofovir analogs & derivatives, Viral Load drug effects, Adenine analogs & derivatives, Cobicistat administration & dosage, Darunavir administration & dosage, Drug Resistance, Viral, Emtricitabine administration & dosage, HIV Infections drug therapy
Abstract

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg is being investigated in two Phase III trials, AMBER (NCT02431247; treatment-naive adults) and EMERALD (NCT02269917; treatment-experienced, virologically suppressed adults). Week 48 AMBER and EMERALD resistance analyses are presented. Postbaseline samples for genotyping/phenotyping were analyzed from protocol-defined virologic failures (PDVFs) with viral load (VL) ≥400 copies/mL at failure/later time points. Post hoc analyses were deep sequencing in AMBER, and HIV-1 proviral DNA from baseline samples (VL <50 copies/mL) in EMERALD. Through week 48 across both studies, no darunavir, primary PI, or tenofovir resistance-associated mutations (RAMs) were observed in HIV-1 viruses of 1,125 participants receiving D/C/F/TAF or 629 receiving boosted darunavir plus emtricitabine/tenofovir-disoproxil-fumarate. In AMBER, the nucleos(t)ide analog reverse transcriptase inhibitor (N(t)RTI) RAM M184I/V was identified in HIV-1 of one participant during D/C/F/TAF treatment. M184V was detected pretreatment as a minority variant (9%). In EMERALD, in participants with prior VF and genoarchive data ( N  = 140; 98 D/C/F/TAF and 42 control), 4% had viruses with darunavir RAMs, 38% with emtricitabine RAMs, mainly at position 184 (41% not fully susceptible to emtricitabine), 4% with tenofovir RAMs, and 21% ≥ 3 thymidine analog-associated mutations (24% not fully susceptible to tenofovir) detected at screening. All achieved VL <50 copies/mL at week 48 or prior discontinuation. D/C/F/TAF has a high genetic barrier to resistance; no darunavir, primary PI, or tenofovir RAMs were observed through 48 weeks in AMBER and EMERALD. Only one postbaseline M184I/V RAM was observed in HIV-1 of an AMBER participant. In EMERALD, baseline archived RAMs to darunavir, emtricitabine, and tenofovir in participants with prior VF did not preclude virologic response.

Published
2020
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results