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Record W3119490951 · doi:10.1093/ofid/ofaa439.1171

985. Impact of Age and Medical Comorbidities on Renal Outcomes in the DISCOVER Trial

2020· article· en· W3119490951 on OpenAlexaff
Eric S. Daar, Jason Brunetta, Éric Cua, Jason Flamm, David M. Asmuth, Christoph C Carter, Yongwu Shao, Pamela Wong, Ramin Ebrahimi, Moupali Das, Diana M. Brainard, Amanda Clarke

Bibliographic record

VenueOpen Forum Infectious Diseases · 2020
Typearticle
Languageen
FieldMedicine
TopicHIV/AIDS drug development and treatment
Canadian institutionsMaple Leaf Medical Clinic
Fundersnot available
KeywordsMedicineRenal functionTenofovir alafenamideInternal medicineDiabetes mellitusCreatinineComorbidityAdverse effectUrologyEndocrinologyImmunology

Abstract

fetched live from OpenAlex

Abstract Background In DISCOVER, emtricitabine/tenofovir alafenamide (F/TAF) was noninferior to F/tenofovir disoproxil fumarate (TDF) for preexposure prophylaxis (PrEP) in men who have sex with men and transgender women, with a superior renal laboratory profile. The differential impact of F/TAF and F/TDF on renal parameters among older individuals and those with medical comorbidities is unknown. Methods DISCOVER randomized participants 1:1 to daily blinded F/TAF or F/TDF. We examined renal outcomes at week 48 including estimated glomerular filtration rate (eGFR) by Cockcroft-Gault, β2 microglobulin (M):Creatinine (Cr) and retinol binding protein (RBP):Cr ratios (markers of proximal renal tubular function), and discontinuations due to investigator reported study drug-related renal adverse events (AEs). Results Median age was 34 years (yrs)(range 18-76), with 12.5% vs 10.9% < 25yrs, 12.2% vs 14.4% ≥ 50yrs, and 1.1% vs 0.9% > 65yrs for F/TAF and F/TDF, respectively. The prevalence of medical comorbidities at baseline were; eGFR < 90mL/min= 9.1% vs 9.3%, diabetes= 2.9% vs 3.3%, and hypertension= 10.5 vs 11.1%, for F/TAF and F/TDF, respectively. eGFR changes by age category and medical comorbidity status are found in the Table. Forty participants had study drug-related renal AEs; 14 with F/TAF and 26 with F/TDF. Of these, 25% were > 50yrs, 20% had baseline eGFR < 90mL/min, 7.5% had history of diabetes, and 22.5% had history of hypertension. β2M:Cr and RBP:Cr changes were more favorable in participants receiving F/TAF, with greater magnitude of difference in older participants (data not shown). Table. Conclusion The DISCOVER trial allows for a large single variable comparison of the two tenofovir prodrugs in the absence of underlying HIV infection and in the absence of third antiretroviral agents. F/TAF was associated with favorable changes in renal biomarkers regardless of age or medical comorbidity. Participants ≥50yrs or with comorbidities were proportionately more likely to develop study drug related renal AEs, but these were present in the minority of cases. Disclosures Eric Daar, MD, BMS (Consultant)Gilead Sciences Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator)Janssen (Consultant)Merck (Consultant, Grant/Research Support)Teva (Consultant)Theratechnology (Consultant)Viiv Healthcare (Consultant, Grant/Research Support) Jason Brunetta, MD, AbbVie (Consultant)Gilead Sciences Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Speaker’s Bureau, Other Financial or Material Support, Conference attendance sponsorship)Janssen (Other Financial or Material Support, Conference attendance sponsorship)Merck (Consultant, Speaker’s Bureau, Other Financial or Material Support, Conference attendance sponsorship)Viiv Healthcare (Consultant, Speaker’s Bureau, Other Financial or Material Support, Conference attendance sponsorship) Eric Cua, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) David Asmuth, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Christoph C. Carter, MD, Gilead Sciences Inc. (Employee, Shareholder) Yongwu Shao, PhD, Gilead Sciences Inc. (Employee, Shareholder) Pamela Wong, MPH, Gilead Sciences Inc. (Employee, Shareholder) Ramin Ebrahimi, MSc, Gilead Sciences Inc. (Employee, Shareholder) Moupali Das, MD, Gilead Sciences Inc. (Employee, Shareholder) Diana M. Brainard, MD, Gilead Sciences (Employee) Amanda Clarke, MD, Gilead Sciences Inc. (Consultant, Scientific Research Study Investigator, Other Financial or Material Support, Conference attendance sponsorship)Viiv Healthcare (Consultant, Other Financial or Material Support, Conference travel sponsorship)

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 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)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation 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 score0.058
Threshold uncertainty score0.468

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
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 head0.026
GPT teacher head0.336
Teacher spread0.309 · 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 teacher head, 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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Citations1
Published2020
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