Evidence map›Paper›PMID 15328117›Full record

ArticleAntimicrobial agents and chemotherapy2004

Clinical emergence of entecavir-resistant hepatitis B virus requires additional substitutions in virus already resistant to Lamivudine.

D J Tenney, S M Levine, R E Rose, A W Walsh, S P Weinheimer, L Discotto, M Plym, K Pokornowski, C F Yu, P Angus and 7 more

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

Article in Antimicrobial agents and chemotherapy, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
145citing papers in PubMed, 7 pooled it
30.8field-weighted citation impact, top 1% 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

145 citing papers in PubMed, 7 syntheses or guidelines pooled it, 537 citations in OpenAlex.

  1. Guideline
  2. Guideline
  3. Pooled it
  4. Management of chronic hepatitis B: Canadian Association for the Study of the Liver consensus guidelines.Canadian journal of gastroenterology = Journal canadien de gastroenterologie · 2012
    Guideline
  5. Guideline
  6. Pooled it
  7. SASLT practice guidelines for the management of hepatitis B virus.Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association
    Guideline
  8. Trial
  9. Trial
  10. Trial
  11. Trial
  12. Trial
  13. Trial
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
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85 more citing papers are in PubMed but not listed here.

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

17 authors at 4 institutions in 3 countries.

D J TenneyBristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Pkwy., Wallingford, CT 06492, USA. daniel.tenney@bms.com
S M Levine
R E Rose
A W Walsh
S P Weinheimer
L Discotto
M Plym
K Pokornowski
C F Yu
P Angus
A Ayres
A Bartholomeusz
W Sievert
G Thompson
N Warner
S Locarnini
R J Colonno
Bristol-Myers Squibb (United States) · USVictorian Infectious Diseases Reference Laboratory · AUBristol-Myers Squibb (Germany) · DEMonash Medical Centre · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Entecavir (ETV) exhibits potent antiviral activity in patients chronically infected with wild-type or lamivudine (3TC)-resistant (3TC(r)) hepatitis B virus (HBV). Among the patients treated in phase II ETV clinical trials, two patients for whom previous therapies had failed exhibited virologic breakthrough while on ETV. Isolates from these patients (arbitrarily designated patients A and B) were analyzed genotypically for emergent substitutions in HBV reverse transcriptase (RT) and phenotypically for reduced susceptibility in cultures and in HBV polymerase assays. After 54 weeks of 3TC therapy, patient A (AI463901-A) received 0.5 mg of ETV for 52 weeks followed by a combination of ETV and 100 mg of 3TC for 89 weeks. Viral rebound occurred at 133 weeks after ETV was started. The 3TC(r) RT substitutions rtV173L, rtL180M, and rtM204V were present at study entry, and the additional substitutions rtI169T and rtM250V emerged during ETV-3TC combination treatment. Reduced ETV susceptibility in vitro required the rtM250V substitution in addition to the 3TC(r) substitutions. For liver transplant patient B (AI463015-B), previous famciclovir, ganciclovir, foscarnet, and 3TC therapies had failed, and RT changes rtS78S/T, rtV173L, rtL180M, rtT184S, and rtM204V were present at study entry. Viral rebound occurred after 76 weeks of therapy with ETV at 1.0 mg, with the emergence of rtT184G, rtI169T, and rtS202I substitutions within the preexisting 3TC(r) background. Reduced susceptibility in vitro was highest when both the rtT184G and the rtS202I changes were combined with the 3TC(r) substitutions. In summary, infrequent ETV resistance can emerge during prolonged therapy, with selection of additional RT substitutions within a 3TC(r) HBV background, leading to reduced ETV susceptibility and treatment failure.

Indexed as

AdultAmino Acid SubstitutionAntiviral AgentsCapsid ProteinsCell Line, TumorCells, CulturedDNA-Directed DNA PolymeraseDrug Resistance, ViralGenotypeGuanineHepatitis BHepatitis B virusHumansLamivudineMaleMiddle AgedAntiviral AgentsCapsid ProteinsDNA-Directed DNA PolymeraseentecavirGuanineLamivudineReverse Transcriptase InhibitorsRNA-Directed DNA Polymerase

Identifiers

PMID15328117
PMCPMC514758
OpenAlexW2126563189

What OpenQuestion holds

Textmetadata
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.