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
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:36 |
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| Enthalten in: |
AIDS research and human retroviruses - 36(2020), 1 vom: 17. Jan., Seite 48-57 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lathouwers, Erkki [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 09.12.2020 Date Revised 04.12.2021 published: Print-Electronic ClinicalTrials.gov: NCT02431247, NCT02269917 Citation Status MEDLINE |
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| doi: |
10.1089/AID.2019.0111 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM301245878 |
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| 245 | 1 | 0 | |a 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 |
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| 500 | |a ClinicalTrials.gov: NCT02431247, NCT02269917 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
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| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 650 | 4 | |a deep sequencing | |
| 650 | 4 | |a efficacy | |
| 650 | 4 | |a resistance | |
| 650 | 4 | |a single-tablet regimen | |
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| 700 | 1 | |a Brown, Kimberley |e verfasserin |4 aut | |
| 700 | 1 | |a Baugh, Bryan |e verfasserin |4 aut | |
| 700 | 1 | |a Ghys, Anne |e verfasserin |4 aut | |
| 700 | 1 | |a Jezorwski, John |e verfasserin |4 aut | |
| 700 | 1 | |a Mohsine, El Ghazi |e verfasserin |4 aut | |
| 700 | 1 | |a Van Landuyt, Erika |e verfasserin |4 aut | |
| 700 | 1 | |a Opsomer, Magda |e verfasserin |4 aut | |
| 700 | 1 | |a De Meyer, Sandra |e verfasserin |4 aut | |
| 700 | 0 | |a AMBER and EMERALD Study Groups |e verfasserin |4 aut | |
| 700 | 1 | |a De Wit, S |e investigator |4 oth | |
| 700 | 1 | |a Florence, E |e investigator |4 oth | |
| 700 | 1 | |a Vandekerckhove, L |e investigator |4 oth | |
| 700 | 1 | |a Vandercam, B |e investigator |4 oth | |
| 700 | 1 | |a Brunetta, J |e investigator |4 oth | |
| 700 | 1 | |a Klein, M |e investigator |4 oth | |
| 700 | 1 | |a Murphy, D |e investigator |4 oth | |
| 700 | 1 | |a Rachlis, A |e investigator |4 oth | |
| 700 | 1 | |a Walmsley, S |e investigator |4 oth | |
| 700 | 1 | |a Ajana, F |e investigator |4 oth | |
| 700 | 1 | |a Cotte, L |e investigator |4 oth | |
| 700 | 1 | |a Girard, P-M |e investigator |4 oth | |
| 700 | 1 | |a Katlama, C |e investigator |4 oth | |
| 700 | 1 | |a Molina, J-M |e investigator |4 oth | |
| 700 | 1 | |a Poizot-Martin, I |e investigator |4 oth | |
| 700 | 1 | |a Raffi, F |e investigator |4 oth | |
| 700 | 1 | |a Rey, D |e investigator |4 oth | |
| 700 | 1 | |a Reynes, J |e investigator |4 oth | |
| 700 | 1 | |a Teicher, E |e investigator |4 oth | |
| 700 | 1 | |a Yazdanpanah, Y |e investigator |4 oth | |
| 700 | 1 | |a Arastéh, K |e investigator |4 oth | |
| 700 | 1 | |a Bickel, M |e investigator |4 oth | |
| 700 | 1 | |a Bogner, J |e investigator |4 oth | |
| 700 | 1 | |a Esser, S |e investigator |4 oth | |
| 700 | 1 | |a Faetkenheuer, G |e investigator |4 oth | |
| 700 | 1 | |a Jessen, H |e investigator |4 oth | |
| 700 | 1 | |a Kern, W |e investigator |4 oth | |
| 700 | 1 | |a Rockstroh, J |e investigator |4 oth | |
| 700 | 1 | |a Spinner, C |e investigator |4 oth | |
| 700 | 1 | |a Stellbrink, H-J |e investigator |4 oth | |
| 700 | 1 | |a Stoehr, A |e investigator |4 oth | |
| 700 | 1 | |a Antinori, A |e investigator |4 oth | |
| 700 | 1 | |a Castelli, F |e investigator |4 oth | |
| 700 | 1 | |a Chirianni, A |e investigator |4 oth | |
| 700 | 1 | |a De Luca, A |e investigator |4 oth | |
| 700 | 1 | |a Di Biagio, A |e investigator |4 oth | |
| 700 | 1 | |a Galli, M |e investigator |4 oth | |
| 700 | 1 | |a Lazzarin, A |e investigator |4 oth | |
| 700 | 1 | |a Maggiolo, F |e investigator |4 oth | |
| 700 | 1 | |a Maserati, R |e investigator |4 oth | |
| 700 | 1 | |a Mussini, C |e investigator |4 oth | |
| 700 | 1 | |a Garlicki, A |e investigator |4 oth | |
| 700 | 1 | |a Gasiorowski, J |e investigator |4 oth | |
| 700 | 1 | |a Halota, W |e investigator |4 oth | |
| 700 | 1 | |a Horban, A |e investigator |4 oth | |
| 700 | 1 | |a Parczewski, M |e investigator |4 oth | |
| 700 | 1 | |a Piekarska, A |e investigator |4 oth | |
| 700 | 1 | |a Belonosova, E |e investigator |4 oth | |
| 700 | 1 | |a Chernova, O |e investigator |4 oth | |
| 700 | 1 | |a Dushkina, N |e investigator |4 oth | |
| 700 | 1 | |a Kulagin, V |e investigator |4 oth | |
| 700 | 1 | |a Ryamova, E |e investigator |4 oth | |
| 700 | 1 | |a Shuldyakov, A |e investigator |4 oth | |
| 700 | 1 | |a Sizova, N |e investigator |4 oth | |
| 700 | 1 | |a Tsybakova, O |e investigator |4 oth | |
| 700 | 1 | |a Voronin, E |e investigator |4 oth | |
| 700 | 1 | |a Yakovlev, A |e investigator |4 oth | |
| 700 | 1 | |a Antela, A |e investigator |4 oth | |
| 700 | 1 | |a Arribas, J R |e investigator |4 oth | |
| 700 | 1 | |a Berenguer, J |e investigator |4 oth | |
| 700 | 1 | |a Casado, J |e investigator |4 oth | |
| 700 | 1 | |a Estrada, V |e investigator |4 oth | |
| 700 | 1 | |a Galindo, M J |e investigator |4 oth | |
| 700 | 1 | |a Garcia Del Toro, M |e investigator |4 oth | |
| 700 | 1 | |a Gatell, J M |e investigator |4 oth | |
| 700 | 1 | |a Gorgolas, M |e investigator |4 oth | |
| 700 | 1 | |a Gutierrez, F |e investigator |4 oth | |
| 700 | 1 | |a Gutierrez, Mdm |e investigator |4 oth | |
| 700 | 1 | |a Negredo, E |e investigator |4 oth | |
| 700 | 1 | |a Pineda, J A |e investigator |4 oth | |
| 700 | 1 | |a Podzamczer, D |e investigator |4 oth | |
| 700 | 1 | |a Portilla Sogorb, J |e investigator |4 oth | |
| 700 | 1 | |a Rivero, A |e investigator |4 oth | |
| 700 | 1 | |a Rubio, R |e investigator |4 oth | |
| 700 | 1 | |a Viciana, P |e investigator |4 oth | |
| 700 | 1 | |a De Los Santos, I |e investigator |4 oth | |
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| 700 | 1 | |a Gazzard, B G |e investigator |4 oth | |
| 700 | 1 | |a Johnson, M A |e investigator |4 oth | |
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| 700 | 1 | |a Reeves, I |e investigator |4 oth | |
| 700 | 1 | |a Waters, L |e investigator |4 oth | |
| 700 | 1 | |a Benson, P |e investigator |4 oth | |
| 700 | 1 | |a Bhatti, L |e investigator |4 oth | |
| 700 | 1 | |a Bredeek, F |e investigator |4 oth | |
| 700 | 1 | |a Crofoot, G |e investigator |4 oth | |
| 700 | 1 | |a Cunningham, D |e investigator |4 oth | |
| 700 | 1 | |a DeJesus, E |e investigator |4 oth | |
| 700 | 1 | |a Eron, J |e investigator |4 oth | |
| 700 | 1 | |a Felizarta, F |e investigator |4 oth | |
| 700 | 1 | |a Franco, R |e investigator |4 oth | |
| 700 | 1 | |a Gallant, J |e investigator |4 oth | |
| 700 | 1 | |a Hagins, D |e investigator |4 oth | |
| 700 | 1 | |a Henry, K |e investigator |4 oth | |
| 700 | 1 | |a Jayaweera, D |e investigator |4 oth | |
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| 700 | 1 | |a Martorell, C |e investigator |4 oth | |
| 700 | 1 | |a McDonald, C |e investigator |4 oth | |
| 700 | 1 | |a McGowan, J |e investigator |4 oth | |
| 700 | 1 | |a Mills, A |e investigator |4 oth | |
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