Evidence map›Paper›PMID 25421485›Full record

ArticleAntimicrobial agents and chemotherapy2015

Impact of drug resistance-associated amino acid changes in HIV-1 subtype C on susceptibility to newer nonnucleoside reverse transcriptase inhibitors.

Adriaan E Basson, Soo-Yon Rhee, Chris M Parry, Ziad El-Khatib, Salome Charalambous, Tulio De Oliveira, Deenan Pillay, Christopher Hoffmann, David Katzenstein, Robert W Shafer and 1 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
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 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing 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

41 citing papers in PubMed, 59 citations in OpenAlex.

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  13. 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

11 authors at 9 institutions in 5 countries.

Adriaan E BassonCentre for HIV and STIs, National Institute for Communicable Diseases (NICD), part of the National Health Laboratory Service (NHLS), Johannesburg, South Africa University of the Witwatersrand, Johannesburg, South Africa.
Soo-Yon RheeDivision of Infectious Diseases, Stanford University Medical Center, Stanford, California, USA.
Chris M ParryAntiviral Unit Virus Reference Department, Health Protection Agency (HPA), London, United Kingdom MRC/UCL Center for Medical Molecular Virology, UCL, London, United Kingdom MRC/UVRI Research Unit on AIDS, Uganda Virus Research Institute, Entebbe, Uganda.
Ziad El-KhatibCentre for HIV and STIs, National Institute for Communicable Diseases (NICD), part of the National Health Laboratory Service (NHLS), Johannesburg, South Africa Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
Salome CharalambousThe Aurum Institute, Johannesburg, South Africa.
Tulio De OliveiraAfrica Centre for Health and Population Studies, University of KwaZulu-Natal, Mtubatuba, South Africa.
Deenan PillayAntiviral Unit Virus Reference Department, Health Protection Agency (HPA), London, United Kingdom MRC/UCL Center for Medical Molecular Virology, UCL, London, United Kingdom.
Christopher HoffmannThe Aurum Institute, Johannesburg, South Africa Johns Hopkins University, Center for TB Research, School of Medicine, Baltimore, Maryland, USA.
David KatzensteinDivision of Infectious Diseases, Stanford University Medical Center, Stanford, California, USA.
Robert W ShaferDivision of Infectious Diseases, Stanford University Medical Center, Stanford, California, USA.
Lynn MorrisCentre for HIV and STIs, National Institute for Communicable Diseases (NICD), part of the National Health Laboratory Service (NHLS), Johannesburg, South Africa University of the Witwatersrand, Johannesburg, South Africa lynnm@nicd.ac.za.
National Health Laboratory Service · ZAStanford University · USAurum Institute · ZAJohns Hopkins University · USMRC Laboratory for Molecular Cell Biology · GBStanford Medicine · USUniversity College London · GBUniversity of KwaZulu-Natal · ZAUniversity of the Witwatersrand · ZA

Funding

PUBLIC HIV DRUG RESISTANCE DATABASER01AI068581 · NIAID · STANFORD UNIVERSITY · PI SHAFER, ROBERT WILLIAM · 2006 to 2017
$6.2M
Medical Research Council MR/K006584/1NIAID NIH HHS AI06858NIAID NIH HHS R01 AI068581Wellcome Trust 097410
6 · The paper itself

Abstract

The objective of this study was to assess the phenotypic susceptibility of HIV-1 subtype C isolates, with nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated amino acid changes, to newer NNRTIs. A panel of 52 site-directed mutants and 38 clinically derived HIV-1 subtype C clones was created, and the isolates were assessed for phenotypic susceptibility to etravirine (ETR), rilpivirine (RPV), efavirenz (EFV), and nevirapine (NVP) in an in vitro single-cycle phenotypic assay. The amino acid substitutions E138Q/R, Y181I/V, and M230L conferred high-level resistance to ETR, while K101P and Y181I/V conferred high-level resistance to RPV. Y181C, a major NNRTI resistance-associated amino acid substitution, caused decreased susceptibility to ETR and, to a lesser extent, RPV when combined with other mutations. These included N348I and T369I, amino acid changes in the connection domain that are not generally assessed during resistance testing. However, the prevalence of these genotypes among subtype C sequences was, in most cases, <1%. The more common EFV/NVP resistance-associated substitutions, such as K103N, V106M, and G190A, had no major impact on ETR or RPV susceptibility. The low-level resistance to RPV and ETR conferred by E138K was not significantly enhanced in the presence of M184V/I, unlike for EFV and NVP. Among patient samples, 97% were resistant to EFV and/or NVP, while only 24% and 16% were resistant to ETR and RPV, respectively. Overall, only a few, relatively rare NNRTI resistance-associated amino acid substitutions caused resistance to ETR and/or RPV in an HIV-1 subtype C background, suggesting that these newer NNRTIs would be effective in NVP/EFV-experienced HIV-1 subtype C-infected patients.

Indexed as

Drug Resistance, ViralHIV-1HumansMutagenesis, Site-DirectedReverse Transcriptase InhibitorsReverse Transcriptase Inhibitors

Identifiers

PMID25421485
PMCPMC4335849
OpenAlexW2149545619

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.