Evidence map›Paper›PMID 25542470›Full record

ArticleJournal of clinical virology : the official publication of the Pan American Society for Clinical Virology2015

Next generation sequencing improves detection of drug resistance mutations in infants after PMTCT failure.

Randall G Fisher, Davey M Smith, Ben Murrell, Ruhan Slabbert, Bronwyn M Kirby, Clair Edson, Mark F Cotton, Richard H Haubrich, Sergei L Kosakovsky Pond, Gert U Van Zyl

Abstract read
In one paragraph

Article in Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 1 pooled it
–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

30 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  8. Review
  9. Article
  10. MiDRMViruses · 2019
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  16. Metagenomic Analysis ofFrontiers in cellular and infection microbiology · 2018
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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

10 authors.

Randall G FisherDivision of Medical Virology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Francie van Zilj Drive, Parow 7500, South Africa.
Davey M SmithDepartment of Medicine, University of California, San Diego, Stein Clinical Research Building #325 (mail code 0679), 9500 Gilman Drive, La Jolla, CA 92093, USA; San Diego Veterans Affairs Healthcare System, (Mail Code 8208), 150 W. Washington Street #100, San Diego, CA 92103, USA.
Ben MurrellDepartment of Medicine, University of California, San Diego, Stein Clinical Research Building #325 (mail code 0679), 9500 Gilman Drive, La Jolla, CA 92093, USA.
Ruhan SlabbertDepartment of Genetics, Stellenbosch University, Private Bag X1, 7602 Matieland, South Africa.
Bronwyn M KirbyInstitute for Microbial Biotechnology and Metagenomics, New Life Sciences Building, 2nd Floor, Core 2, University of the Western Cape, Modderdam Road, P/Bag X17, Bellville 7530, South Africa.
Clair EdsonDepartment Paediatrics and Child Health, Stellenbosch University and Tygerberg Children's Hospital, Francie van Zijl Drive, Parow 7500, South Africa.
Mark F CottonDepartment Paediatrics and Child Health, Stellenbosch University and Tygerberg Children's Hospital, Francie van Zijl Drive, Parow 7500, South Africa; Children's Infectious Diseases Clinical Research Unit (KIDCRU) Ward J8, Tygerberg Hospital, Francie van Zijl Drive, Parow 7500, South Africa.
Richard H HaubrichUniversity of California, San Diego, AVRC, 220 Dickinson, Suite A, San Diego, CA 92103, USA.
Sergei L Kosakovsky PondDepartment of Medicine, University of California, San Diego, Stein Clinical Research Building #325 (mail code 0679), 9500 Gilman Drive, La Jolla, CA 92093, USA.
Gert U Van ZylDivision of Medical Virology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Francie van Zilj Drive, Parow 7500, South Africa; National Health Laboratory Service, Tygerberg, Francie van Zijl Drive, Parow 7500, South Africa. Electronic address: guvz@sun.ac.za.

Funding

VirologyP30AI036214 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Maile Ann Young Karris · 1994 to 2026
$78.4M
UCSD Department of Medicine HIV/AIDS Clinical Trials UnitUM1AI069432 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TIMOTHY J. WILKIN · 2012 to 2026
$50.4M
UCSD Department of Medicine HIV/AIDS Clinical Trials UnitU01AI069432 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BENSON, CONSTANCE ANN · 2007 to 2011
$19.3M
Molecular Epidemiology for HIV Prevention for Drug Users and Other Risk Groups DP1DA034978 · NIDA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SMITH, DAVID MITCHELL · 2012 to 2016
$4.1M
A Multi-Site Investigation into the Effect of HIV Clade on Neurocognitive ImpairmR01MH083552 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SMITH, DAVID MITCHELL · 2008 to 2012
$3.3M
HyPhy: Molecular Evolutionary AnalysesR01GM093939 · NIGMS · TEMPLE UNIV OF THE COMMONWEALTH · PI MUSE, SPENCER V., POND, SERGEI L KOSAKOVSKY · 2010 to 2018
$2.5M
Effects of Host and Viral Aging on NeurocognitionR01MH097520 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SMITH, DAVID MITCHELL · 2012 to 2016
$2.0M
Improving Antiretroviral Management for HIVK24AI064086 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HAUBRICH, RICHARD H · 2006 to 2015
$1.8M
Mentoring Translational Research in HIVK24AI100665 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SMITH, DAVID MITCHELL · 2012 to 2021
$1.5M
NIAID NIH HHS AI036214NIAID NIH HHS AI064086NIAID NIH HHS AI069432NIAID NIH HHS AI100665NIAID NIH HHS K24 AI064086NIAID NIH HHS K24 AI100665NIAID NIH HHS P30 AI036214NIAID NIH HHS U01 AI069432NIAID NIH HHS UM1 AI069432NIDA NIH HHS DA034978NIDA NIH HHS DP1 DA034978NIGMS NIH HHS R01 GM093939NIMH NIH HHS MH083552NIMH NIH HHS MH097520NIMH NIH HHS R01 MH083552NIMH NIH HHS R01 MH097520
6 · The paper itself

Abstract

backgroundNext generation sequencing (NGS) allows the detection of minor variant HIV drug resistance mutations (DRMs). However data from new NGS platforms after Prevention-of-Mother-to-Child-Transmission (PMTCT) regimen failure are limited.

objectiveTo compare major and minor variant HIV DRMs with Illumina MiSeq and Life Technologies Ion Personal Genome Machine (PGM) in infants infected despite a PMTCT regimen. STUDY

designWe conducted a cross-sectional study of NGS for detecting DRMs in infants infected despite a zidovudine (AZT) and Nevirapine (NVP) regimen, before initiation of combination antiretroviral therapy. Sequencing was performed on PCR products from plasma samples on PGM and MiSeq platforms. Bioinformatic analyses were undertaken using a codon-aware version of the Smith-Waterman mapping algorithm and a mixture multinomial error filtering statistical model.

resultsOf 15 infants, tested at a median age of 3.4 months after birth, 2 (13%) had non-nucleoside reverse transcriptase inhibitor (NNRTI) DRMs (K103N and Y181C) by bulk sequencing, whereas PGM detected 4 (26%) and MiSeq 5 (30%). NGS enabled the detection of additional minor variant DRMs in the infant with K103N. Coverage and instrument quality scores were higher with MiSeq, increasing the confidence of minor variant calls.

conclusionsNGS followed by bioinformatic analyses detected multiple minor variant DRMs in HIV-1 RT among infants where PMTCT failed. The high coverage of MiSeq and high read quality improved the confidence of identified DRMs and may make this platform ideal for minor variant detection.

Indexed as

Drug Resistance, ViralAnti-HIV AgentsAntiretroviral Therapy, Highly ActiveCD4 Lymphocyte CountComputational BiologyFemaleGenotypeHigh-Throughput Nucleotide SequencingHIV-1HIV InfectionsHumansInfantInfant, NewbornInfectious Disease Transmission, VerticalMaleMicrobial Sensitivity TestsAnti-HIV AgentsRNA, ViralHIV-1 drug resistanceMinor variant antiretroviral drug resistance mutationsNevirapineNext generation sequencingNon-nucleoside reverse transcriptase inhibitor resistancePrevention of mother to child transmission

Identifiers

PMID25542470
PMCPMC4279108

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Registered trials

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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.