Evidence map›Paper›PMID 20539818›Full record

ArticlePloS one2010

Nucleic acid template and the risk of a PCR-Induced HIV-1 drug resistance mutation.

Vici Varghese, Elijah Wang, Farbod Babrzadeh, Michael H Bachmann, Rajin Shahriar, Tommy Liu, Svetlana Jean M Mappala, Baback Gharizadeh, W Jeffrey Fessel, David Katzenstein and 2 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
3.4field-weighted citation impact, top 7% 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

42 citing papers in PubMed, 69 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Amino Acid Prevalence of HIV-1AIDS research and human retroviruses · 2019
    Article
  6. Article
  7. Article
  8. Comparison of anJournal of clinical microbiology · 2018
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Next generation sequencing improves detection of drug resistance mutations in infants after PMTCT failure.Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology · 2015
    Article
  17. Article
  18. Article
  19. Article
  20. 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

12 authors at 2 institutions in 1 country.

Vici VargheseDepartment of Medicine, Stanford University School of Medicine, Stanford, California, United States of America. viciv@stanford.edu
Elijah Wang
Farbod Babrzadeh
Michael H Bachmann
Rajin Shahriar
Tommy Liu
Svetlana Jean M Mappala
Baback Gharizadeh
W Jeffrey Fessel
David Katzenstein
Seble Kassaye
Robert W Shafer
Stanford University · USKaiser Permanente · US

Funding

HIV-1 Drug Resistance in Different SubtypesR01AI066922 · NIAID · STANFORD UNIVERSITY · PI KANTOR, RAMI, KATZENSTEIN, DAVID ALLENBERG · 2008 to 2012
$3.6M
IDENTIFICATION OF MULTIDRUG RESISTANT HIV1 ISOLATESR01AI046148 · NIAID · STANFORD UNIVERSITY · PI SHAFER, ROBERT WILLIAM · 1999 to 2008
$2.4M
NIAID NIH HHS AI46148NIAID NIH HHS R01 AI046148NIAID NIH HHS R01 AI066922
6 · The paper itself

Abstract

backgroundThe HIV-1 nucleoside RT inhibitor (NRTI)-resistance mutation, K65R confers intermediate to high-level resistance to the NRTIs abacavir, didanosine, emtricitabine, lamivudine, and tenofovir; and low-level resistance to stavudine. Several lines of evidence suggest that K65R is more common in HIV-1 subtype C than subtype B viruses. METHODS AND

findingsWe performed ultra-deep pyrosequencing (UDPS) and clonal dideoxynucleotide sequencing of plasma virus samples to assess the prevalence of minority K65R variants in subtype B and C viruses from untreated individuals. Although UDPS of plasma samples from 18 subtype C and 27 subtype B viruses showed that a higher proportion of subtype C viruses contain K65R (1.04% vs. 0.25%; p<0.001), limiting dilution clonal sequencing failed to corroborate its presence in two of the samples in which K65R was present in >1.5% of UDPS reads. We therefore performed UDPS on clones and site-directed mutants containing subtype B- and C-specific patterns of silent mutations in the conserved KKK motif encompassing RT codons 64 to 66 and found that subtype-specific nucleotide differences were responsible for increased PCR-induced K65R mutation in subtype C viruses.

conclusionsThis study shows that the RT KKK nucleotide template in subtype C viruses can lead to the spurious detection of K65R by highly sensitive PCR-dependent sequencing techniques. However, the study is also consistent with the subtype C nucleotide template being inherently responsible for increased polymerization-induced K65R mutations in vivo.

Indexed as

MutationTemplates, GeneticBase SequenceDNA PrimersDNA, ViralDrug Resistance, ViralHIV-1Mutagenesis, Site-DirectedPlasmidsPolymerase Chain ReactionDNA PrimersDNA, Viral

Identifiers

PMID20539818
PMCPMC2881873
OpenAlexW2076709337

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.