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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

2019· article· en· W2955217622 on OpenAlex
Joseph J. Eron, Chloe Orkin, Douglas Cunningham, Federico Pulido, Frank A. Post, Erkki Lathouwers, Veerle Hufkens, John Jezorwski, Romana Petrovic, Kimberley Brown, Erika Van Landuyt, Magda Opsomer, Éric Florence, Michel Moutschen, Eric Van Wijngaerden, Linos Vandekerckhove, Jason Brunetta, Brian Conway, Marina B. Klein, Daniel Murphy, Anita Rachlis, Stephen D. Shafran, Sharon Walmsley, F. Ajana, Laurent Cotte, P.-M. Girardy, Christine Katlama, Jean‐Michel Molina, Isabelle Poizot‐Martin, François Raffi, D. Rey, Jacques Reynes, Elina Teicher, Yazdan Yazdanpanah, Jacek Gąsiorowski, Waldemar Halota, Andrzéj Horban, Anna Piekarska, Anita Witor, José Ramón Arribas, Ignacio Valero, Juan Berenguer, José L. Casado, José M. Gatell, Félix Gutiérrez, Marı́a José Galindo, María del Mar Gutiérrez, José Antonio Iribarren, Hernando Knobel, Eugènia Negredo, Juan A. Pineda, Daniel Podzamczer, C Ricart, Antonio Rivero, I Santos Gil, Anders Blaxhult, Leo Flamholc, Magnus Gisslén, Anders Thalme, Jan Fehr, Andri Rauch, Marcel Stoeckle, Amanda Clarke, B Gazzard, Mikayla Johnson, Andrew Ustianowski, Laura Waters, Joseph I. Bailey, Paul Benson, Laveeza Bhatti, Indira Brar, U. Fritz Bredeek, Cynthia Brinson, Gordon Crofoot, E DeJesus, Craig Dietz, Robin Dretler, Franco Felizarta, Carl J. Fichtenbaum, Joel E. Gallant, Joseph Gathe, Debbie Hagins, S Henn, W. Keith Henry, Gregory Huhn, Mamta K. Jain, Christopher Lucasti, Claudia Martorell, Cheryl McDonald, Anthony Mills, Javier O Morales-Ramirez, Karam Mounzer, Ronald Nahass, H Olivet, Olayemi Osiyemi, D Prelutsky, Moti Ramgopal, Bruce Rashbaum, Gary Richmond, P. Ruane, A. Scarsella, Anita Scribner, Peter Shalit, David Shamblaw, Jihad Slim, K. Tashima, Gene W. Voskuhl, Derek Ward, Aimee Wilkin, Jerome De Vente

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueAntiviral Research · 2019
Typearticle
Languageen
FieldMedicine
TopicHIV/AIDS drug development and treatment
Canadian institutionsUniversity of AlbertaHealth Sciences CentreSunnybrook Health Science CentreUniversity Health NetworkUniversity of TorontoVancouver Infectious Diseases CentreCanada Research ChairsMcGill UniversityMaple Leaf Medical Clinic
FundersJanssen PharmaceuticalsRaymond and Beverly Sackler Institute for Biological, Physical and Engineering Sciences, Yale UniversityArthur FoundationJohnson and JohnsonGilead SciencesMerckYale University
KeywordsDarunavirEmtricitabineTenofovir alafenamideMedicineInternal medicineAdverse effectCobicistatGastroenterologyViral loadVirologyHuman immunodeficiency virus (HIV)Antiretroviral therapy

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.005
metaresearch head score (Gemma)0.004
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: Randomized trial
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.040
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0050.004
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0020.000
Bibliometrics0.0010.002
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.034
GPT teacher head0.328
Teacher spread0.294 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it