Evidence map›Paper›PMID 25385110›Full record

ArticleAntimicrobial agents and chemotherapy2015

In vitro resistance selection with doravirine (MK-1439), a novel nonnucleoside reverse transcriptase inhibitor with distinct mutation development pathways.

Meizhen Feng, Deping Wang, Jay A Grobler, Daria J Hazuda, Michael D Miller, Ming-Tain Lai

Open access · bronzeAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
3.6field-weighted citation impact, top 6% 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

47 citing papers in PubMed, 108 citations in OpenAlex.

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  18. 2022 update of the drug resistance mutations in HIV-1.Topics in antiviral medicine · 2022
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  19. Cryo-EM structures of wild-type and E138K/M184I mutant HIV-1 RT/DNA complexed with inhibitors doravirine and rilpivirine.Proceedings of the National Academy of Sciences of the United States of America · 2022
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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

6 authors at 1 institution in 1 country.

Meizhen FengDepartment of Antiviral Research, Merck Research Laboratories, West Point, Pennsylvania, USA.
Deping WangDepartment of Chemistry Modeling & Informatics, Merck Research Laboratories, West Point, Pennsylvania, USA.
Jay A GroblerDepartment of Antiviral Research, Merck Research Laboratories, West Point, Pennsylvania, USA.
Daria J HazudaDepartment of Antiviral Research, Merck Research Laboratories, West Point, Pennsylvania, USA.
Michael D MillerDepartment of Antiviral Research, Merck Research Laboratories, West Point, Pennsylvania, USA.
Ming-Tain LaiDepartment of Antiviral Research, Merck Research Laboratories, West Point, Pennsylvania, USA mingtain_lai@merck.com.
United States Military Academy · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Doravirine (DOR, formerly known as MK-1439) is a human immunodeficiency type 1 virus (HIV-1) nonnucleoside reverse transcriptase inhibitor (NNRTI) that is currently in phase 2b clinical trials. In vitro resistance selection of subtype B virus (MT4-green fluorescent protein [GFP] cells), as well as subtype A and C viruses (MT4-GFP/CCR5 cells) was conducted with DOR, rilpivirine (RPV), and efavirine (EFV) under low-multiplicity-of-infection conditions in a 96-well format. Resistance selection was performed with escalating concentrations of the NNRTIs ranging from the 95% effective concentration (1 × EC(95)) to 1,000 × EC(95) in the presence of 10% fetal bovine serum. In the resistance selection of subtype B virus with DOR, a V106A mutant virus led to two mutation pathways, followed by the emergence separately of either F227L or L234I. In the resistance selection of subtype A and C viruses, similar mutation development pathways were detected, in which a V106A or V106M mutant was also the starting virus in the pathways. Mutations that are commonly associated with RPV and EFV in clinical settings were also identified in subtype B viruses such as the E138K and K103N mutants, respectively, in this in vitro resistance selection study. The susceptibility of subtype B mutant viruses selected by DOR, RPV, and EFV to NNRTIs was evaluated. Results suggest that mutant viruses selected by DOR are susceptible to RPV and EFV and mutants selected by RPV and EFV are susceptible to DOR. When the replication capacity of the V106A mutant was compared with that of the wild-type (WT) virus, the mutant virus was 4-fold less fit than the WT virus.

Indexed as

MutationAnti-HIV AgentsDrug Resistance, ViralHEK293 CellsHIV-1HumansNitrilesPyridazinesPyridonesPyrimidinesReverse Transcriptase InhibitorsRilpivirineSelection, GeneticTriazolesAnti-HIV AgentsdoravirineetravirineNitrilesPyridazinesPyridonesPyrimidinesReverse Transcriptase InhibitorsRilpivirineTriazoles

Identifiers

PMID25385110
PMCPMC4291404
OpenAlexW2077754502

What OpenQuestion holds

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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.