Evidence map›Paper›PMID 27666440›Full record

ArticleJournal of viral hepatitis2017

Analysis of resistance-associated substitutions in acute hepatitis C virus infection by deep sequencing across six genotypes and three continents.

A A Eltahla, C Rodrigo, B Betz-Stablein, J Grebely, T Applegate, F Luciani, J Schinkel, G J Dore, K Page, J Bruneau and 11 more

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

Article in Journal of viral hepatitis, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.9field-weighted citation impact, top 13% 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

4 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Article
  3. Observational
  4. 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

21 authors at 10 institutions in 4 countries.

A A EltahlaSchool of Medical Sciences, Faculty of Medicine, UNSW Australia, Sydney, NSW, Australia.
C RodrigoSchool of Medical Sciences, Faculty of Medicine, UNSW Australia, Sydney, NSW, Australia.
B Betz-StableinSchool of Medical Sciences, Faculty of Medicine, UNSW Australia, Sydney, NSW, Australia.
J GrebelyThe Kirby Institute, UNSW Australia, Sydney, NSW, Australia.
T ApplegateThe Kirby Institute, UNSW Australia, Sydney, NSW, Australia.
F LucianiSchool of Medical Sciences, Faculty of Medicine, UNSW Australia, Sydney, NSW, Australia.
J SchinkelDepartment of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, Center for Infection and Immunity Amsterdam, Academic Medical Center, Meibergdreef, Amsterdam, The Netherlands.
G J DoreThe Kirby Institute, UNSW Australia, Sydney, NSW, Australia.
K PageDepartment of Internal Medicine, University of New Mexico, Albuquerque, NM, USA.
J BruneauCRCHUM, Université de Montréal, Montreal, QC, Canada.
M D MorrisDepartment of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA.
A L CoxDepartment of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
A Y KimHarvard Medical School, Boston, MA, USA.
N H ShoukryCRCHUM, Université de Montréal, Montreal, QC, Canada.
G M LauerHarvard Medical School, Boston, MA, USA.
L MaherThe Kirby Institute, UNSW Australia, Sydney, NSW, Australia.
M HellardBurnet Institute, Melbourne, Vic, Australia.
M PrinsDepartment of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, Center for Infection and Immunity Amsterdam, Academic Medical Center, Meibergdreef, Amsterdam, The Netherlands.
A R LloydSchool of Medical Sciences, Faculty of Medicine, UNSW Australia, Sydney, NSW, Australia.
R A BullSchool of Medical Sciences, Faculty of Medicine, UNSW Australia, Sydney, NSW, Australia.
InC3 Study Group
UNSW Sydney · AUData61 · AUHarvard University · USUniversité de Montréal · CAAcademic Medical Center · NLGGD Amsterdam · NLJohns Hopkins Bayview Medical Center · USMonash University · AUUniversity of California, San Francisco · USUniversity of New Mexico · US

Funding

Acute Hepatitis C Infection in Young InjectorsR01DA016017 · NIDA · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI PAGE, KIMBERLY · 2002 to 2018
$14.0M
The role of NK cells during acute HCV infection and antiviral therapyU19AI066345 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI KIM, ARTHUR Y · 2005 to 2014
$8.5M
Scientific CoreU19AI088791 · NIAID · JOHNS HOPKINS UNIVERSITY · PI COX, ANDREA L · 2010 to 2020
$8.2M
Treatment of recently acquired hepatitis C virus infectionR01DA015999 · NIDA · UNIVERSITY OF NEW SOUTH WALES · PI DORE, GREGORY JOHN · 2003 to 2014
$3.7M
International Collaborative of prospective studies of HIV and Hepatitis in IDUR01DA031056 · NIDA · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI PAGE, KIMBERLY · 2011 to 2015
$2.2M
Understanding the interpersonal context of HIV/HCV risk within injecting dyadsK01DA037802 · NIDA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MORRIS, MEGHAN D · 2014 to 2018
$913k
NIAID NIH HHS U19 AI066345NIAID NIH HHS U19 AI088791NIDA NIH HHS K01 DA037802NIDA NIH HHS R01 DA015999NIDA NIH HHS R01 DA016017NIDA NIH HHS R01 DA031056
6 · The paper itself

Abstract

Several direct-acting antivirals (DAAs) have been approved for the treatment of chronic hepatitis C virus (HCV) infections, opening the door to highly effective interferon-free treatment regimens. Resistance-associated substitutions (RASs) have been reported both in treatment-naïve patients and following treatment with protease (NS3), phosphoprotein (NS5A) and polymerase (NS5B) inhibitors. The prevalence of naturally occurring RASs in untreated HCV-infected individuals has mostly been analysed in those infected with genotype 1 (GT1), in the late phase of infection, and only within limited regions of the genome. Furthermore, the geographic distribution of RASs remains poorly characterized. In this study, we used next-generation sequencing to analyse full-length HCV genomes for the prevalence of RASs in acute HCV infections identified in nine international prospective cohorts. RASs were analysed in 179 participants infected with all six major HCV genotypes (GT1-GT6), and the geographic distribution of RASs was assessed in 107 GT1a and GT3a samples. While RASs were detected at varied frequencies across the three genomic regions, and between genotypes, RASs relevant to multiple DAAs in the leading IFN-free regimens were rarely detected in combination. Low-frequency RASs (<10% of the viral population) were also shown to have a GT-specific distribution. The main RASs with geographic associations were NS3 Q80K in GT1a samples and NS5B N142T in GT3a. These data provide the backdrop for prospective surveillance of RASs during DAA treatment scale-up.

Indexed as

Amino Acid SubstitutionDrug Resistance, ViralGenotypeAdultDEAD-box RNA HelicasesFemaleGene FrequencyHepacivirusHepatitis CHigh-Throughput Nucleotide SequencingHumansMaleMutant ProteinsNucleoside-TriphosphatasePhylogeographyProspective StudiesDEAD-box RNA HelicasesMutant ProteinsNS3 protein, hepatitis C virusNS-5 protein, hepatitis C virusNucleoside-TriphosphataseRNA-Dependent RNA PolymeraseSerine EndopeptidasesViral Nonstructural ProteinsViral ProteasesantiviralDAAhepatitis C virusinhibitorsresistance

Identifiers

PMID27666440
PMCPMC6421067
OpenAlexW2521531894

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.