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Record W2791842602 · doi:10.1093/jcag/gwy008.181

A180 IMPROVED RENAL LABORATORY PARAMETERS IN CHB PATIENTS TREATED WITH TAF COMPARED WITH TDF

2018· article· en· W2791842602 on OpenAlexaff
Florence Wong, Mashroor Khan, K. Agarwal, Norihiro Furusyo, Jae Seok Hwang, John Flaherty, K Kim

Bibliographic record

VenueJournal of the Canadian Association of Gastroenterology · 2018
Typearticle
Languageen
FieldMedicine
TopicHIV/AIDS drug development and treatment
Canadian institutionsGilead Sciences (Canada)Toronto General Hospital
Fundersnot available
KeywordsMedicineInternal medicineKidney diseaseRenal functionTenofovir alafenamideUrologyCreatinineDiabetes mellitusTenofovirGastroenterologyStage (stratigraphy)PlaceboEndocrinologyViral loadHuman immunodeficiency virus (HIV)ImmunologyPathologyAntiretroviral therapy

Abstract

fetched live from OpenAlex

Tenofovir Disoproxil Fumarate (TDF) treatment results in high rates of viral suppression with no described resistance; however its use has been associated with a deterioration in bone mineral density and eGFR over time. TAF, a novel prodrug of tenofovir (TFV), has better stability in plasma resulting in lower systemic TFV exposures than TDF. Phase 3 studies of TAF in CHB demonstrated lower declines in eGFR compared to TDF over 48 weeks of treatment. Here, we further characterize the clinical renal benefits of TAF compared to TDF. In two identically-designed Phase 3 studies of TAF (Study 110 in HBeAg positive and Study 108 in HBeAg negative patients), patients were randomized 2:1 to TAF 25 mg QD or TDF 300 mg QD, each with matching placebo, and treated for 96 weeks. After Week 96, patients receive open label TAF for 48 weeks. Renal parameters including eGFR calculated by Cockcroft-Gault and CKD-EPI were evaluated throughout the study period. Chronic kidney disease (CKD) staging was categorized according to the NKF KDOQI guidelines (Stage 1: eGFR ≥ 90ml/min; Stage 2: eGFR 60–90 ml/min; Stage 3 eGFR 30–59 ml/min). Evaluated risk factors for kidney disease included older age and comorbidities of hypertension, cardiovascular disease and diabetes. Multivariate analysis was performed using backwards stepwise approach. Baseline demographics between TAF and TDF groups in both studies were generally balanced for risk factors for kidney disease. At week 48, patients treated with TAF had smaller changes in creatinine (median change 0.01 mg/dL for TAF and 0.02 mgdL for TDF; p=0.012) and eGFRCG (median change -1.2 mL/min for TAF and -5.4 mL/min for TDF; p<0.001) during 48 weeks of treatment. The number of patients who had >25% creatinine clearance reductions was also greater in the TDF arm versus the TAF arm (14.5% vs 8.7%, p=0.002). Using the stages of CKD, a higher percentage of patients treated with TDF had one or more stage worsening in renal function at Week 48 (10.2% vs 6.5%; p=0.06). Among patients at highest risk for kidney disease (older age and comorbidities of hypertension, cardiovascular disease or diabetes), significantly more patients had worsening of renal function in TDF treated patients compared to TAF treated patients.Multivariate analysis of worsening renal function by CKD stage identified higher baseline eGFR, male gender, and Age > 50 as Independent predictors. In patients with CHB, TAF therapy is associated with improvement of renal safety versus TDF. The benefits of TAF may be particularly evident in patients at higher risk of GFR decline. Gilead Sciences, Inc.

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.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.000

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 head0.005
GPT teacher head0.201
Teacher spread0.195 · 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

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations0
Published2018
Admission routes1
Has abstractyes

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