2024 updates to the Québec antiretroviral therapeutic drug monitoring guidelines: Key changes over 10 years
Bibliographic record
Abstract
7 days or standard of care (SoC).Throughout the study period, clinical data, safety evaluations, virology and pharmacokinetics were collected at predefined timepoints.FVP was quantified using validated LC-MS methods with FVP concentrations expressed as ng/mL.The primary outcome was safety, with toxicity considered to be unacceptable if the probability of 30% or greater doselimiting toxicity related to FVP over controls was 25% or greater, as calculated by the Bayesian model.Secondary outcomes included clinical progression scores, pharmacokinetic parameters and virological endpoints.Results: Of 30 participants screened, 24 were enrolled between 10 September 2022 and 1 November 2023 [10/24 female; median age was 74 years (range 52-93)].FVP was well tolerated at all doses, despite a high background rate of adverse events reflecting the frailty and comorbidity of participants.As in previous studies of FVP, transient hyperuricaemia was observed in patients in the treatment cohorts.This was asymptomatic in all cases and resolved on completion of treatment.There were no serious adverse events or severe (≥grade 3) adverse events that were deemed possibly or probably related to FVP by an independent, blinded assessor.The probability of greater than 30% excess toxicity over controls at 2400 mg, as estimated by the Bayesian model, was 2.7%.PK exposures increased proportionally to dose, although there was notable variability between participants within each cohort.Significant FVP accumulation in plasma occurred; for cohorts 1-4 respectively (600/1200/1800/2400 mg BD), median day 1 clast (6-12 h post-infusion) was 500 (below LLQ)/4242/5109/ 23 573 ng/mL, and median day 3 clast was 1335/38 730/47 000/ 125 468 ng/mL. Conclusions:In this phase Ib multiple ascending dose study of a novel IV formulation of FVP, we administered higher sustained doses than previously used, up to 2400 mg twice daily.Despite the frail and comorbid nature of the population admitted to hospital with COVID-19, IV FVP was safe and well tolerated at this dose.Plasma PK studies demonstrated accumulation at days 3 and 5, in contrast to previous studies that employed loading doses.Significant PK variability was noted between individuals.Although well tolerated, based on PK data, we report and recent FVP EC90 data, and we do not recommend FVP for later stage clinical trial evaluation as a treatment for COVID-19.FVP remains a potentially important candidate as a treatment for emerging viral threats including pandemic influenza.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.019 | 0.066 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.005 | 0.007 |
| Science and technology studies | 0.003 | 0.002 |
| Scholarly communication | 0.006 | 0.003 |
| Open science | 0.005 | 0.002 |
| Research integrity | 0.011 | 0.009 |
| Insufficient payload (model declined to judge) | 0.034 | 0.015 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".