Evidence map›Paper›PMID 26936587›Full record

Trial reportHaemophilia : the official journal of the World Federation of Hemophilia2016

Viral dynamic modelling of Hepatitis C and resistance-associated variants in haemophiliacs.

K E Sherman, R Ke, S D Rouster, E A Abdel-Hameed, C Park, J Palascak, A S Perelson

Open access · greenAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Haemophilia : the official journal of the World Federation of Hemophilia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
0.2field-weighted citation impact, top 44% of its field
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

0 citing papers in PubMed, 1 citations in OpenAlex.

No citing paper in PubMed yet.

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

7 authors at 2 institutions in 1 country.

K E ShermanDivision of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
R KeTheoretical Biology & Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM, USA.
S D RousterDivision of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
E A Abdel-HameedDivision of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
C ParkDivision of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
J PalascakDivision of Hematology & Oncology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
A S PerelsonTheoretical Biology & Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM, USA.
University of Cincinnati Medical Center · USLos Alamos National Laboratory · US

Funding

LCenter for Clinical and Translational Science and TrainingUL1TR001425 · NCATS · UNIVERSITY OF CINCINNATI · PI HEUBI, JAMES E., KISSELA, BRETT M · 2015 to 2024
$37.5M
REPRODUCTIVE AND DEVELOPMENTAL TOXICOLOGY RESEARCHP30ES006096 · NIEHS · UNIVERSITY OF CINCINNATI · PI YADAV, JAGJIT S · 1992 to 2022
$35.4M
Stem Cell/Organoid and Genome Editing CoreP30DK078392 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI LEE ARMISTEAD DENSON · 2007 to 2026
$24.4M
Cincinnati Center for Clinical and Translational Sciences and TrainingUL1TR000077 · NCATS · UNIVERSITY OF CINCINNATI · PI HEUBI, JAMES E., TSEVAT, JOEL · 2012 to 2014
$9.9M
Modeling Viral and T Lymphocyte DynamicsR01OD011095 · OD · TRIAD NATIONAL SECURITY, LLC · PI PERELSON, ALAN S · 2012 to 2024
$5.0M
Immune System Modeling/HIVR01AI028433 · NIAID · UNIVERSITY OF CALIF-LOS ALAMOS NAT LAB · PI PERELSON, ALAN S · 1990 to 2021
$3.7M
Mentorship in Liver DiseaseK24DK070528 · NIDDK · UNIVERSITY OF CINCINNATI · PI SHERMAN, KENNETH E · 2005 to 2014
$1.4M
Viral kinetic models of HCV clearance in hemophiliacs treated with telaprevirR34HL109334 · NHLBI · UNIVERSITY OF CINCINNATI · PI SHERMAN, KENNETH E · 2012 to 2013
$713k
NCATS NIH HHS UL1 TR000077NCATS NIH HHS UL1 TR001425NHLBI NIH HHS R34 HL109334NIAID NIH HHS R01 AI028433NIDDK NIH HHS K24 DK070528NIDDK NIH HHS P30 DK078392NIEHS NIH HHS P30 ES006096NIH HHS R01 OD011095
6 · The paper itself

Abstract

aimChronic hepatitis C virus (HCV) infection is an important source of morbidity and mortality among haemophiliacs. Limited data are available regarding treatment intervention using direct-acting antivirals (DAAs) and theoretical concerns regarding accumulation of drug-associated resistance variants (RAVs) remain. We conducted a pilot study of treatment with telaprevir/pegylated interferon-alfa/ribavirin to evaluate treatment response and the role of lead-in DAA therapy on mutational selection of resistance variants.

methodsUltra-deep sequence analysis was performed at baseline, 48 hours and 168 hours after treatment initiation.

resultsNo dominant RAVs were identified at baseline, but low-level RAVs were noted at baseline in all subjects. Viral dynamic models were used to assess treatment responses. The efficacy parameter (Ɛ) for lead-in ranged from 0 to 0.9745 (mean = 0.514). Subsequent addition of telaprevir resulted in a mean efficacy of more than 0.999. This was comparable to subjects who started all three medications simultaneously. A total of 80% achieved SVR. While rapid shifts in the RAV population following DAA initiation were observed, treatment failure associated with A156V was observed in only one patient. Adverse event profiles were similar to that observed in non-haemophilia cohorts. There was no evidence of factor inhibitor formation. There was no evidence that lead-in provided benefit in terms of response efficacy.

conclusionThese data support DAA-based therapy in those with inherited bleeding disorders.

Indexed as

Models, BiologicalAntiviral AgentsDrug Resistance, ViralGenotypeHemophilia AHepacivirusHepatitis CHumansOligopeptidesReal-Time Polymerase Chain ReactionRNA, ViralSequence Analysis, DNATreatment FailureViral LoadAntiviral AgentsOligopeptidesRNA, Viraltelaprevirdirect-acting antiviralshaemophiliaHCVresistance-associated variantstreatment responseviral dynamic models

Identifiers

PMID26936587
PMCPMC4958555
OpenAlexW2290610223

What OpenQuestion holds

Textmetadata
LicenceTDM
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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.