Single Dose IV Peramivir Treatment in Pediatric Influenza: Lack of Development of Influenza Virus Variants with Reduced Susceptibility to Peramivir
Bibliographic record
Abstract
Peramivir (PVR) is a potent neuraminidase inhibitor (NAI) with in vitro activity against all influenza virus subtypes. Previous studies demonstrated the efficacy and safety of peramivir as a single dose intravenous (IV) treatment for acute uncomplicated influenza in adults. A phase 3 study compared age-appropriate single dose IV PVR to 5 days of oral oseltamivir (OSE) (4:1 randomization, stratified by age) in pediatric subjects age 0–17 years within 48 hours of acute uncomplicated influenza symptom onset. Influenza infection and subtype was confirmed by PCR. In vitro susceptibility of cultured virus to PVR, OSE and zanamivir (ZVR) from paired baseline/ post-treatment nasopharyngeal (NP) swabs was performed with a MUNANA assay. Sequence analysis of NA and hemagglutinin (HA) genes was performed from uncultured virus. 122 subjects were enrolled up to a cutoff date of March 31, 2017 (<2 yrs, n = 7; 2-<7yrs, n = 37; 7-<13 yrs, n = 48; 13–17 yrs, n = 30). Data is shown on 108 subjects randomized prior to the 2016–17 season, of which 101 (94%) received study drug. Full data will be reported. Influenza was confirmed in 75 (74%) subjects who received study drug: A/H1N1, n = 31 (41%); B, n = 27 (36%); A/H3N2, n = 15 (20%); A/indeterminate and A/H1N1/ B co-infected, 1 each. Baseline IC50 s for each subtype are summarized: Two treatment-emergent substitutions were detected in NA or HA genes of PVR-treated subjects: a NA S67A (reversion to wild type) in an influenza B virus and a HA V496V/F mixture in an A/H1N1 virus. Neither substitution was associated with a resistant phenotype. Among PVR treated subjects, no changes were observed in the last positive post-baseline sample PVR median IC50 compared with baseline and no individual subject treated with PVR had an IC50 fold-change from baseline greater than 1.63. Peramivir had the greatest potency of 3 NAIs tested for all baseline virus subtypes in the order: PVR < ZVR < OSE. Treatment with a single dose of IV PVR was not associated with development of resistance to the drug in this pediatric population. M. È. Hamelin, BioCryst Pharmaceuticals: Collaborator, Research support; Y. Abed, BioCryst Pharmaceuticals: Collaborator, Research support; J. Carbonneau, BioCryst Pharmaceuticals: Collaborator, Research support; R. Jeeninga, BioCryst Pharmaceuticals: Collaborator, Research support; S. Smits, BioCryst Pharmaceuticals: Collaborator, Research support; S. Kulenovic, BioCryst Pharmaceuticals: Collaborator, Research support; K. Borroto-Esoda, BioCryst Pharmaceuticals: Consultant, Consulting fee; R. Taylor, BioCryst Pharmaceuticals: Employee, Salary; P. Collis, BioCryst Pharmaceuticals: Employee, Salary; G. Boivin, BioCryst Pharmaceuticals: Collaborator, Research support
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
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".