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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.

Authors
  • Lathouwers, Erkki1
  • Wong, Eric Y2
  • Brown, Kimberley1
  • Baugh, Bryan3
  • Ghys, Anne1
  • Jezorwski, John4
  • Mohsine, El Ghazi1
  • Van Landuyt, Erika1
  • Opsomer, Magda1
  • De Meyer, Sandra1
  • 1 Janssen Pharmaceutica NV, Beerse, Belgium. , (Belgium)
  • 2 Janssen Scientific Affairs, LLC, Titusville, New Jersey. , (Jersey)
  • 3 Janssen Research & Development LLC, Raritan, New Jersey. , (Jersey)
  • 4 Janssen Research & Development, Pennington, New Jersey. , (Jersey)
Type
Published Article
Journal
AIDS Research and Human Retroviruses
Publisher
Mary Ann Liebert
Publication Date
Jan 01, 2020
Volume
36
Issue
1
Pages
48–57
Identifiers
DOI: 10.1089/AID.2019.0111
PMID: 31516033
Source
Medline
Keywords
Language
English
License
Unknown

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.

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