Evidence map›Paper›PMID 24603872›Full record

Trial reportPloS one2014

Comparison of illumina and 454 deep sequencing in participants failing raltegravir-based antiretroviral therapy.

Jonathan Z Li, Brad Chapman, Patrick Charlebois, Oliver Hofmann, Brian Weiner, Alyssa J Porter, Reshmi Samuel, Saran Vardhanabhuti, Lu Zheng, Joseph Eron and 21 more

Open access · goldAbstract readClinical TrialComparative Study
In one paragraph

Trial report in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

13 citing papers in PubMed, 35 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Impact of Human Immunodeficiency Virus Type 1 Minority Variants on the Virus Response to a Rilpivirine-Based First-line Regimen.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018
    Article
  6. Efficient In Vivo Liver-Directed Gene Editing Using CRISPR/Cas9.Molecular therapy : the journal of the American Society of Gene Therapy · 2018
    Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Review
  13. 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

31 authors at 5 institutions in 2 countries.

Jonathan Z LiDivision of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
Brad ChapmanHarvard School of Public Health, Boston, Massachusetts, United States of America.
Patrick CharleboisBroad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
Oliver HofmannHarvard School of Public Health, Boston, Massachusetts, United States of America.
Brian WeinerBroad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
Alyssa J PorterHarvard School of Public Health, Boston, Massachusetts, United States of America.
Reshmi SamuelDivision of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America; Department of Virology, University of KwaZulu-Natal, National Health Laboratory Service, Durban, South Africa.
Saran VardhanabhutiHarvard School of Public Health, Boston, Massachusetts, United States of America.
Lu ZhengHarvard School of Public Health, Boston, Massachusetts, United States of America.
Joseph EronDivision of Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina, United States of America.
Babafemi TaiwoDivision of Infectious Diseases, Northwestern University, Chicago, Illinois, United States of America.
Michael C ZodyBroad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
Matthew R HennBroad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
Daniel R KuritzkesDivision of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
Winston HideHarvard School of Public Health, Boston, Massachusetts, United States of America.
ACTG A5262 Study Team
Cara C WilsonUniversity of Colorado.
Baiba I BerzinsNorthwestern University.
Edward P AcostaUniversity of Alabama at Birmingham.
Barbara BastowACTG Operations Center, Social & Scientific Systems, Inc.
Peter S KimNational Institute of Allergy and Infectious Diseases.
Sarah W ReadNational Institute of Allergy and Infectious Diseases.
Jennifer JanikFrontier Science & Technology Research Foundation.
Debra S MeresNational Institute of Allergy and Infectious Diseases.
Michael M LedermanCase Western Reserve University.
Lori Mong-KryspinOhio State University.
Karl E ShawHenry Ford Hospital CRS.
Louis G ZimmermanUniversity of Colorado CRS.
Randi LeavittMerck.
Guy De La RosaTibotec.
Amy JenningsACTG Operations Center.
Broad Institute · USBrigham and Women's Hospital · USNational Health Laboratory Service · ZANorthwestern University · USUniversity of North Carolina at Chapel Hill · US

Funding

Leadership and Operations Center (LOC), AIDS Clinical Trials Group (ACTG); LOC 1/UM1AI068636 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Joseph J Eron, RAJESH T GANDHI · 2011 to 2026
$1073.1M
Statistical and Data Management Center (SDMC), AIDS Clinical Trials Group (ACTG)UM1AI068634 · NIAID · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Marlene Ann Cooper, Michael David Hughes · 2011 to 2026
$246.6M
AIDS Clinical Trials Group NetworkU01AI068636 · NIAID · SOCIAL AND SCIENTIFIC SYSTEMS, INC. · PI KURITZKES, DANIEL R. · 2006 to 2010
$147.1M
Validation, CLIA and Qualification (VQC): Enhancing the RS ratio as a tool for AIDS Clinical Trial Group (ACTG) tuberculosis trialsUM1AI106701 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Grace M Aldrovandi · 2014 to 2026
$116.8M
The impact of HIV viral diversity and cellular immunity on HIV pathogenesisP30AI060354 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI ROBERT A. PARKER · 2004 to 2026
$94.4M
HARVARD CLINICAL AND TRANSLATIONAL SCIENCE CENTER (UL1)UL1RR025758 · NCRR · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2008 to 2011
$91.4M
Virology, Immunology, and Microbiology CoreP30AI050410 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DAVID M. MARGOLIS · 2001 to 2026
$76.9M
Statistical and Data Management Center for the AIDS Clinical Trials GroupU01AI068634 · NIAID · HARVARD SCHOOL OF PUBLIC HEALTH · PI HUGHES, MICHAEL DAVID · 2006 to 2010
$71.9M
University of North Carolina Global HIV Prevention and Treatment Clinical Trials Unit 2024 SupplementUM1AI069423 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Joseph J Eron, MINA CHRISTINE HOSSEINIPOUR · 2012 to 2026
$71.8M
Harvard Medical School Vaccine Clinical Trials UnitUM1AI069412 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI Lindsey Robert Baden, Daniel R. Kuritzkes · 2012 to 2026
$57.2M
Clinical and Translational Science Collaborative of ClevelandUL1TR000439 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$50.0M
Northwestern University Clinical Trial UnitUM1AI069471 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Chad J Achenbach · 2012 to 2026
$24.6M
NCATS NIH HHS UL1 TR000439NCRR NIH HHS UL1 RR 025758NCRR NIH HHS UL1 RR025758NIAID NIH HHS K08 AI100699NIAID NIH HHS P30 AI050410NIAID NIH HHS P30 AI060354NIAID NIH HHS U01 AI068634NIAID NIH HHS U01 AI068636NIAID NIH HHS UM1 AI068634NIAID NIH HHS UM1 AI068636NIAID NIH HHS UM1 AI069412NIAID NIH HHS UM1 AI069423NIAID NIH HHS UM1 AI069471NIAID NIH HHS UM1 AI106701
6 · The paper itself

Abstract

backgroundThe impact of raltegravir-resistant HIV-1 minority variants (MVs) on raltegravir treatment failure is unknown. Illumina sequencing offers greater throughput than 454, but sequence analysis tools for viral sequencing are needed. We evaluated Illumina and 454 for the detection of HIV-1 raltegravir-resistant MVs.

methodsA5262 was a single-arm study of raltegravir and darunavir/ritonavir in treatment-naïve patients. Pre-treatment plasma was obtained from 5 participants with raltegravir resistance at the time of virologic failure. A control library was created by pooling integrase clones at predefined proportions. Multiplexed sequencing was performed with Illumina and 454 platforms at comparable costs. Illumina sequence analysis was performed with the novel snp-assess tool and 454 sequencing was analyzed with V-Phaser.

resultsIllumina sequencing resulted in significantly higher sequence coverage and a 0.095% limit of detection. Illumina accurately detected all MVs in the control library at ≥0.5% and 7/10 MVs expected at 0.1%. 454 sequencing failed to detect any MVs at 0.1% with 5 false positive calls. For MVs detected in the patient samples by both 454 and Illumina, the correlation in the detected variant frequencies was high (R2 = 0.92, P<0.001). Illumina sequencing detected 2.4-fold greater nucleotide MVs and 2.9-fold greater amino acid MVs compared to 454. The only raltegravir-resistant MV detected was an E138K mutation in one participant by Illumina sequencing, but not by 454.

conclusionsIn participants of A5262 with raltegravir resistance at virologic failure, baseline raltegravir-resistant MVs were rarely detected. At comparable costs to 454 sequencing, Illumina demonstrated greater depth of coverage, increased sensitivity for detecting HIV MVs, and fewer false positive variant calls.

Indexed as

MutationAnti-HIV AgentsDrug Resistance, ViralHigh-Throughput Nucleotide SequencingHIV-1HIV InfectionsHumansPyrrolidinonesRaltegravir PotassiumTreatment FailureAnti-HIV AgentsPyrrolidinonesRaltegravir Potassium

Identifiers

PMID24603872
PMCPMC3946168
OpenAlexW2097691899

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.