Evidence map›Paper›PMID 26555159›Full record

Trial reportAntiviral therapy2016

Modelling the interaction between danoprevir and mericitabine in the treatment of chronic HCV infection.

Laetitia Canini, Jeremie Guedj, Anushree Chatterjee, Annabelle Lemenuel-Diot, Patrick F Smith, Alan S Perelson

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Antiviral therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Laetitia CaniniTheoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM, USA.
Jeremie Guedj
Anushree Chatterjee
Annabelle Lemenuel-Diot
Patrick F Smith
Alan S Perelson

Funding

Collaborative Integration of HCV Molecular Virology and Mathematical ModelingR01AI078881 · NIAID · UNIVERSITY OF ILLINOIS AT CHICAGO · PI PERELSON, ALAN S, UPRICHARD, SUSAN L. · 2011 to 2025
$7.5M
Pilot Project ProgramP30GM110907 · NIGMS · UNIVERSITY OF NEW MEXICO · PI MILLER, ROBERT D · 2014 to 2018
$5.4M
Modeling Viral and T Lymphocyte DynamicsR01OD011095 · OD · TRIAD NATIONAL SECURITY, LLC · PI PERELSON, ALAN S · 2012 to 2024
$5.0M
COBRE Center for Evolutionary and Theoretical ImmunologyP20GM103452 · NIGMS · UNIVERSITY OF NEW MEXICO · PI LOKER, ERIC SAMUEL · 2012 to 2013
$4.2M
Immune System Modeling/HIVR01AI028433 · NIAID · UNIVERSITY OF CALIF-LOS ALAMOS NAT LAB · PI PERELSON, ALAN S · 1990 to 2021
$3.7M
Immune System Modeling/HIVR37AI028433 · NIAID · UNIVERSITY OF CALIF-LOS ALAMOS NAT LAB · PI PERELSON, ALAN S · 2002 to 2011
$2.4M
Collaborative Integration of HCV Molecular Virology and Mathematical ModelingR56AI078881 · NIAID · UNIVERSITY OF ILLINOIS AT CHICAGO · PI PERELSON, ALAN S, UPRICHARD, SUSAN L. · 2010 to 2010
$421k
Biotechnology and Biological Sciences Research Council 1698:BB/L001330/1NIAID NIH HHS R01 AI028433NIAID NIH HHS R01 AI078881NIAID NIH HHS R37 AI028433NIAID NIH HHS R56 AI078881NIGMS NIH HHS P20 GM103452NIGMS NIH HHS P30 GM110907NIH HHS R01 OD011095
6 · The paper itself

Abstract

backgroundModelling HCV RNA decline kinetics under therapy has proven useful for characterizing treatment effectiveness.

methodsHere we model HCV viral kinetics (VK) in 72 patients given a combination of danoprevir, a protease inhibitor, and mericitabine, a nucleoside polymerase inhibitor, for 14 days in the INFORM-1 trial. A biphasic VK model with time-varying danoprevir and mericitabine effectiveness and Bliss independence for characterizing the interaction between both drugs provided the best fit to the VK data.

resultsThe average final antiviral effectiveness of the drug combination varied between 0.998 for 100 mg three times daily of danoprevir and 500 mg twice daily of mericitabine and 0.9998 for 600 mg twice daily of danoprevir and 1,000 mg twice daily of mericitabine. Using the individual parameters estimated from the VK data collected over 2 weeks, we were not able to reproduce the low sustained virological response rates obtained in a more recent study where patients were treated with a combination of mericitabine and ritonavir-boosted danoprevir for 24 weeks.

conclusionsThis suggests that drug-resistant viruses emerge after 2 weeks of treatment and that longer studies are necessary to provide accurate predictions of longer treatment outcomes.

Indexed as

Models, BiologicalAntiviral AgentsCyclopropanesDeoxycytidineDose-Response Relationship, DrugDrug InteractionsDrug Therapy, CombinationGenotypeHepacivirusHepatitis C, ChronicHumansIsoindolesLactamsLactams, MacrocyclicProlineRNA, Viral2'-fluoro-2'-methyl-3',5'-diisobutyryldeoxycytidineAntiviral AgentsCyclopropanesdanoprevirDeoxycytidineIsoindolesLactamsLactams, MacrocyclicProlineRNA, ViralSulfonamides

Identifiers

PMID26555159
PMCPMC4862948

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.