Evidence map›Paper›PMID 21288824›Full record

ArticleThe Journal of infectious diseases2011

Deep sequencing to infer HIV-1 co-receptor usage: application to three clinical trials of maraviroc in treatment-experienced patients.

Luke C Swenson, Theresa Mo, Winnie W Y Dong, Xiaoyin Zhong, Conan K Woods, Mark A Jensen, Alexander Thielen, Douglass Chapman, Marilyn Lewis, Ian James and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of infectious diseases, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed
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

78 citing papers in PubMed, 151 citations in OpenAlex.

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  20. Human Immunodeficiency Virus Drug Resistance: 2018 Recommendations of the International Antiviral Society-USA Panel.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019
    Article

18 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 4 countries.

Luke C SwensonBC Centre for Excellence in HIV/AIDS, Vancouver, Canada.
Theresa Mo
Winnie W Y Dong
Xiaoyin Zhong
Conan K Woods
Mark A Jensen
Alexander Thielen
Douglass Chapman
Marilyn Lewis
Ian James
Jayvant Heera
Hernan Valdez
P Richard Harrigan
AIDS Vancouver · CAPfizer (United States) · USPfizer (United Kingdom) · GBMax Planck Institute for Informatics · DE

Funding

Canadian Institutes of Health Research
6 · The paper itself

Abstract

backgroundThe Maraviroc versus Optimized Therapy in Viremic Antiretroviral Treatment-Experienced Patients (MOTIVATE) studies compared maraviroc versus placebo in treatment-experienced patients with CCR5-using (R5) human immunodeficiency virus type 1 (HIV-1), screened using the original Trofile assay. A subset with non-R5 HIV infection entered the A4001029 trial. We retrospectively examined the performance of a genotypic tropism assay based on deep sequencing of the HIV env V3 loop in predicting virologic response to maraviroc in these trials.

methodsV3 amplicons were prepared from 1827 screening plasma samples and sequenced on a Roche/454 GS-FLX to a depth of >3000 sequences/sample. Samples were considered non-R5 if ≥2% of their viral population scored greater than or equal to -4.75 or ≤3.5 using the PSSM(x4/R5) or geno2pheno algorithms, respectively.

resultsDeep sequencing identified more than twice as many maraviroc recipients as having non-R5 HIV, compared with the original Trofile. With use of genotyping, we determined that 49% of maraviroc recipients with R5 HIV at screening had a week 48 viral load <50 copies/mL versus 26% of recipients with non-R5. Corresponding percentages were 46% and 23% with screening by Trofile. In cases in which screening assays differed, median week 8 log₁₀ copies/mL viral load decrease favored 454. Other parameters predicted by genotyping included likelihood of changing to non-R5 tropism.

conclusionsThis large study establishes deep V3 sequencing as a promising tool for identifying treatment-experienced individuals who could benefit from CCR5-antagonist-containing regimens.

Indexed as

Viral TropismAnti-HIV AgentsClinical Trials as TopicCyclohexanesenv Gene Products, Human Immunodeficiency VirusGenotypeHigh-Throughput Nucleotide SequencingHIV-1HIV InfectionsHumansMaravirocReceptors, CCR5Receptors, HIVRetrospective StudiesRNA, ViralTriazolesAnti-HIV AgentsCyclohexanesenv Gene Products, Human Immunodeficiency VirusMaravirocReceptors, CCR5Receptors, HIVRNA, ViralTriazoles

Identifiers

PMID21288824
PMCPMC3071057
OpenAlexW2110388384

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.