Evidence map›Paper›PMID 28379449›Full record

ArticleThe Journal of antimicrobial chemotherapy2017

An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs.

Erasmus Smit, Ellen White, Duncan Clark, Duncan Churchill, Hongyi Zhang, Simon Collins, Deenan Pillay, Caroline Sabin, Mark Nelson, Alan Winston and 4 more

Abstract read
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In one paragraph

Article in The Journal of antimicrobial chemotherapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

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

7 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
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

14 authors.

Erasmus SmitPublic Health Laboratory Birmingham, Public Health England, Heartlands Hospital, Birmingham, UK.
Ellen WhiteMRC CTU at UCL, University College London, London, UK.
Duncan ClarkBarts and The London NHS Trust, London, UK.
Duncan ChurchillBrighton and Sussex University Hospitals NHS Trust, Brighton, UK.
Hongyi ZhangPublic Health Laboratory Cambridge, Public Health England, Addenbrooke's Hospital, Cambridge, UK.
Simon CollinsHIV i-Base, London, UK.
Deenan PillayResearch Department of Infection, Division of Infection and Immunity, University College London, London, UK.
Caroline SabinResearch Department of Infection and Population Health London, University College London, London, UK.
Mark NelsonChelsea and Westminster Hospital, London, UK.
Alan WinstonSection of Infectious Diseases, Department of Medicine, Imperial College London, London, UK.
Sophie JoseResearch Department of Infection and Population Health London, University College London, London, UK.
Anna TostevinResearch Department of Infection and Population Health London, University College London, London, UK.
David T DunnResearch Department of Infection and Population Health London, University College London, London, UK.
UK HIV Drug Resistance Database and the UK Collaborative HIV Cohort

Funding

Medical Research Council G0000199Medical Research Council G0600337Medical Research Council G0900274Medical Research Council M004236Medical Research Council MC_UU_12023/15Medical Research Council MR/M004236/1
6 · The paper itself

Abstract

Objectives: HIV-1 subtype C might have a greater propensity to develop K65R mutations in patients with virological failure compared with other subtypes. However, the strong association between viral subtype and confounding factors such as exposure groups and ethnicity affects the calculation of this propensity. We exploited the diversity of viral subtypes within the UK to undertake a direct comparative analysis. Patients and methods: We analysed only sequences with major IAS-defined mutations from patients with virological failure. Prevalence of K65R was related to subtype and exposure to the NRTIs that primarily select for this mutation (tenofovir, abacavir, didanosine and stavudine). A multivariate logistic regression model quantified the effect of subtype on the prevalence of K65R, adjusting for previous and current exposure to all four specified drugs. Results: Subtype B patients ( n  =   3410) were mostly MSM (78%) and those with subtype C ( n  =   810) were mostly heterosexual (82%). K65R was detected in 7.8% of subtype B patients compared with 14.2% of subtype C patients. The subtype difference in K65R prevalence was observed irrespective of NRTI exposure and K65R was frequently selected by abacavir, didanosine and stavudine in patients with no previous exposure to tenofovir. Multivariate logistic regression confirmed that K65R was significantly more common in subtype C viruses (adjusted OR = 2.02, 95% CI = 1.55-2.62, P  <   0.001). Conclusions: Patients with subtype C HIV-1 have approximately double the frequency of K65R in our database compared with other subtypes. The exact clinical implications of this finding need to be further elucidated.

Indexed as

MutationAbacavirAdultAnti-HIV AgentsAntiretroviral Therapy, Highly ActiveDidanosineDideoxynucleosidesDrug Resistance, ViralFemaleGenetic Association StudiesGenotypeHIV-1HIV InfectionsHumansMaleMultivariate AnalysisAbacavirAnti-HIV AgentsDidanosineDideoxynucleosidesReverse Transcriptase InhibitorsStavudineTenofovir

Identifiers

PMID28379449
PMCPMC5890671

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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.