Evidence map›Paper›PMID 20445200›Full record

ArticleScience translational medicine2010

Rapid emergence of protease inhibitor resistance in hepatitis C virus.

Libin Rong, Harel Dahari, Ruy M Ribeiro, Alan S Perelson

Open access · greenAbstract read
In one paragraph

Article in Science translational medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 papers.

0numbers the graph read from it
0cells of the map it votes in
161citing papers in PubMed
23.8field-weighted citation impact, top 1% 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

161 citing papers in PubMed, 357 citations in OpenAlex.

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101 more citing papers are in PubMed but not listed here.

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

4 authors at 2 institutions in 1 country.

Libin RongTheoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
Harel Dahari
Ruy M Ribeiro
Alan S Perelson
Los Alamos National Laboratory · USUniversity of Illinois Chicago · US

Funding

UNM COBRE: THEORETICAL STUDY OF SPECIFICITY OF RNA SILENCING MECHANISMP20RR018754 · NCRR · UNIVERSITY OF NEW MEXICO · PI LOKER, ERIC SAMUEL · 2003 to 2011
$16.7M
HIV Antiretroviral Therapy and Hepatic InjuryR01AI065256 · NIAID · UNIVERSITY OF CINCINNATI · PI SHERMAN, KENNETH E · 2006 to 2019
$5.5M
Modeling Viral and T Lymphocyte DynamicsR01OD011095 · OD · TRIAD NATIONAL SECURITY, LLC · PI PERELSON, ALAN S · 2012 to 2024
$5.0M
MODELING VIRAL AND T LYMPHOCYTE DYNAMICSR01RR006555 · NCRR · UNIVERSITY OF CALIF-LOS ALAMOS NAT LAB · PI PERELSON, ALAN S · 1991 to 2011
$3.9M
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
Core Center for Quantitative BiologyP30EB011339 · NIBIB · OAKLAND UNIVERSITY · PI ROTH, BRADLEY JOHN · 2009 to 2010
$722k
HIV Antiretroviral Therapy and Hepatic InjuryR56AI065256 · NIAID · UNIVERSITY OF CINCINNATI · PI SHERMAN, KENNETH E · 2014 to 2014
$535k
NCRR NIH HHS P20 RR018754NCRR NIH HHS P20-RR18754NCRR NIH HHS R01 RR006555NCRR NIH HHS RR06555-18NIAID NIH HHS AI065256NIAID NIH HHS AI28433-19NIAID NIH HHS R01 AI028433NIAID NIH HHS R01 AI065256NIAID NIH HHS R37 AI028433NIAID NIH HHS R56 AI065256NIBIB NIH HHS P30 EB011339NIBIB NIH HHS P30-EB011339NIH HHS R01 OD011095
6 · The paper itself

Abstract

About 170 million people worldwide are infected with hepatitis C virus (HCV). The current standard therapy leads to sustained viral elimination in only approximately 50% of the treated patients. Telaprevir, an HCV protease inhibitor, has substantial antiviral activity in patients with chronic HCV infection. However, in clinical trials, drug-resistant variants emerge at frequencies of 5 to 20% of the total virus population as early as the second day after the beginning of treatment. Here, using probabilistic and viral dynamic models, we show that such rapid emergence of drug resistance is expected. We calculate that all possible single- and double-mutant viruses preexist before treatment and that one additional mutation is expected to arise during therapy. Examining data from a clinical trial of telaprevir therapy for HCV infection in detail, we show that our model fits the observed dynamics of both drug-sensitive and drug-resistant viruses and argue that therapy with only direct antivirals will require drug combinations that have a genetic barrier of four or more mutations.

Indexed as

Drug Resistance, ViralMutationAntiviral AgentsClinical Trials as TopicDrug DesignDrug Therapy, CombinationGenome, ViralHepacivirusHepatocytesHumansInhibitory Concentration 50Interferon-alphaInterferon alpha-2OligopeptidesPolyethylene GlycolsProtease InhibitorsAntiviral AgentsInterferon-alphaInterferon alpha-2Oligopeptidespeginterferon alfa-2aPolyethylene GlycolsProtease InhibitorsRecombinant Proteinstelaprevir

Identifiers

PMID20445200
PMCPMC3033690
OpenAlexW2164211111

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.