Evidence map›Paper›PMID 19734799›Full record

ArticleJournal of acquired immune deficiency syndromes (1999)2009

Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors.

Vici Varghese, Rajin Shahriar, Soo-Yon Rhee, Tommy Liu, Birgitte B Simen, Michael Egholm, Bozena Hanczaruk, Lisbeth A Blake, Baback Gharizadeh, Farbod Babrzadeh and 3 more

Abstract read
In one paragraph

Article in Journal of acquired immune deficiency syndromes (1999), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 1 pooled it
7.0field-weighted citation impact, top 2% 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

53 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Full-spectrum HIV drug resistance mutation detection by high-resolution complete pol gene sequencing.Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology · 2023
    Article
  4. HIV and Drug-Resistant Subtypes.Microorganisms · 2023
    Review
  5. Review
  6. Article
  7. Article
  8. Comparison of anJournal of clinical microbiology · 2018
    Article
  9. Article
  10. Article
  11. HIV-1 drug resistance and resistance testing.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2016
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Deep sequencing: becoming a critical tool in clinical virology.Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology · 2014
    Review
  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

13 authors at 1 institution in 1 country.

Vici VargheseDepartment of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. viciv@stanford.edu
Rajin Shahriar
Soo-Yon Rhee
Tommy Liu
Birgitte B Simen
Michael Egholm
Bozena Hanczaruk
Lisbeth A Blake
Baback Gharizadeh
Farbod Babrzadeh
Michael H Bachmann
W Jeffrey Fessel
Robert W Shafer
Stanford University · US

Funding

PUBLIC HIV DRUG RESISTANCE DATABASER01AI068581 · NIAID · STANFORD UNIVERSITY · PI SHAFER, ROBERT WILLIAM · 2006 to 2017
$6.2M
IDENTIFICATION OF MULTIDRUG RESISTANT HIV1 ISOLATESR01AI046148 · NIAID · STANFORD UNIVERSITY · PI SHAFER, ROBERT WILLIAM · 1999 to 2008
$2.4M
PUBLIC HIV DRUG RESISTANCE DATABASER56AI068581 · NIAID · STANFORD UNIVERSITY · PI SHAFER, ROBERT WILLIAM · 2013 to 2013
$729k
NIAID NIH HHS AI068581NIAID NIH HHS AI46148NIAID NIH HHS R01 AI046148NIAID NIH HHS R01 AI068581NIAID NIH HHS R56 AI068581
6 · The paper itself

Abstract

objectivesK103N, the most common nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant mutation in patients with transmitted resistance and in patients receiving a failing NNRTI-containing regimen, is fully susceptible to the new NNRTI, etravirine. Therefore, we sought to determine how often NNRTI-resistant mutations other than K103N occur as minority variants in plasma samples for which standard genotypic resistance testing detects K103N alone.

methodsWe performed ultradeep pyrosequencing (UDPS; 454 Life Sciences a Roche Company, Branford, CT) of plasma virus samples from 13 treatment-naive and 20 NNRTI-experienced patients in whom standard genotypic resistance testing revealed K103N but no other major NNRTI-resistance mutations.

resultsSamples from 0 of 13 treatment-naive patients vs. 7 of 20 patients failing an NNRTI-containing regimen had minority variants with major etravirine-associated NNRTI-resistant mutations (P = 0.03, Fisher exact test): Y181C (7.0%), Y181C (3.6%) + G190A (3.2%), L100I (14%), L100I (32%) + 190A (5.4%), K101E (3.8%) + G190A (4.9%), K101E (4.0%) + G190S (4.8%), and G190S (3.1%).

conclusionsIn treatment-naive patients, UDPS did not detect additional major NNRTI-resistant mutations suggesting that etravirine may be effective in patients with transmitted K103N. In NNRTI-experienced patients, UDPS often detected additional major NNRTI-resistant mutations suggesting that etravirine may not be fully active in patients with acquired K103N.

Indexed as

Drug Resistance, Multiple, ViralAnti-HIV AgentsDrug Therapy, CombinationGenetic VariationGenotypeHIV-1HIV InfectionsHIV Reverse TranscriptaseHumansMutationNitrilesPyridazinesPyrimidinesAnti-HIV AgentsetravirineHIV Reverse TranscriptaseNitrilesPyridazinesPyrimidines

Identifiers

PMID19734799
PMCPMC2809083
OpenAlexW2168518701

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.