Evidence map›Paper›PMID 25608585›Full record

ArticleThe Journal of antimicrobial chemotherapy2015

Performance of commonly used genotypic assays and comparison with phenotypic assays of HIV-1 coreceptor tropism in acutely HIV-1-infected patients.

Elisa Rita Ceresola, Silvia Nozza, Michela Sampaolo, Angela Rosa Pignataro, Diego Saita, Roberto Ferrarese, Marco Ripa, Wenjie Deng, James I Mullins, Enzo Boeri and 5 more

Open access · bronzeAbstract readComparative StudyEvaluation Study
In one paragraph

Article in The Journal of antimicrobial chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.0field-weighted citation impact, top 26% 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

9 citing papers in PubMed, 13 citations in OpenAlex.

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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

15 authors at 4 institutions in 2 countries.

Elisa Rita CeresolaUniversity Vita-Salute San Raffaele, Milan, Italy Laboratory of Microbiology, Ospedale San Raffaele, IRCCS, Milan, Italy.
Silvia NozzaDepartment of Infectious and Tropical Diseases, Ospedale San Raffaele, IRCCS, Milan, Italy.
Michela SampaoloLaboratory of Microbiology, Ospedale San Raffaele, IRCCS, Milan, Italy.
Angela Rosa PignataroLaboratory of Microbiology, Ospedale San Raffaele, IRCCS, Milan, Italy.
Diego SaitaLaboratory of Microbiology, Ospedale San Raffaele, IRCCS, Milan, Italy.
Roberto FerrareseLaboratory of Microbiology, Ospedale San Raffaele, IRCCS, Milan, Italy.
Marco RipaDepartment of Infectious and Tropical Diseases, Ospedale San Raffaele, IRCCS, Milan, Italy.
Wenjie DengDepartment of Microbiology, University of Washington, Seattle, WA, USA.
James I MullinsDepartment of Microbiology, University of Washington, Seattle, WA, USA.
Enzo BoeriLaboratory of Microbiology, Ospedale San Raffaele, IRCCS, Milan, Italy.
Giuseppe TambussiDepartment of Infectious and Tropical Diseases, Ospedale San Raffaele, IRCCS, Milan, Italy.
Antonio TonioloUniversity of Insubria Medical School, Department of Biotechnology and Life Sciences, Varese, Italy.
Adriano LazzarinUniversity Vita-Salute San Raffaele, Milan, Italy Department of Infectious and Tropical Diseases, Ospedale San Raffaele, IRCCS, Milan, Italy.
Massimo ClementiUniversity Vita-Salute San Raffaele, Milan, Italy Laboratory of Microbiology, Ospedale San Raffaele, IRCCS, Milan, Italy.
Filippo CanducciLaboratory of Microbiology, Ospedale San Raffaele, IRCCS, Milan, Italy University of Insubria Medical School, Department of Biotechnology and Life Sciences, Varese, Italy canducci.filippo@gmail.com.
IRCCS Ospedale San Raffaele · ITVita-Salute San Raffaele University · ITUniversity of Insubria · ITUniversity of Washington · US

Funding

University of Washington/Fred Hutch Center for AIDS ResearchP30AI027757 · NIAID · UNIVERSITY OF WASHINGTON · PI Kenneth Sherr · 1988 to 2026
$104.9M
Viral Determinants of HIV-1 Transmission in African HeterosexualsP01AI057005 · NIAID · UNIVERSITY OF WASHINGTON · PI COREY, LAWRENCE · 2003 to 2014
$20.5M
Role of proviral loci in HIV latencyR01AI125026 · NIAID · UNIVERSITY OF WASHINGTON · PI MULLINS, JAMES IVAN · 2016 to 2019
$3.4M
NIAID NIH HHS P01 AI057005NIAID NIH HHS P30 AI027757NIAID NIH HHS R01 AI125026
6 · The paper itself

Abstract

objectivesAlthough founder viruses in primary HIV-1 infections (PHIs) typically use the CCR5 coreceptor (R5-tropic), 3%-19% of subjects also harbour CXCR4-using viruses (X4-tropic), making tropism determination before CCR5 antagonist usage mandatory. Genotypic methods can be used to accurately determine HIV-1 tropism in chronically infected patients.

methodsWe compared the results of genotypic methods [geno2pheno, PSSMx4r5 including a novel nucleotide-input version (ntPSSM) and distant segments (ds)Kernel] to predict coreceptor usage in a cohort of 67 PHIs. Specimens with discrepant results were phenotypically tested after cloning the V3 gene region into proviral backbones. Recombinant viruses were used to infect U87 indicator cell lines bearing CD4 and either CCR5 or CXCR4.

resultsGeno2pheno10%, PSSMx4r5 and (ds)Kernel gave identical predictions in 85% of cases. Geno2pheno10% predicted the presence of CXCR4 viruses in 18% of patients. Two patients were predicted to carry X4-tropic viruses by all algorithms and X4-tropic viruses were detected in at least one of the recombinant AD8 or NL4-3 backbone-based assays. Ten samples resulted in discordant predictions with at least one algorithm. Full concordance between tropism prediction by using population sequencing and phenotypic assays was observed only with ntPSSM. Geno2pheno prediction and the phenotypic assay gave the same results in a minority of 'discordant' patients.

conclusionsCompared with both PSSMx4r5 versions, (ds)Kernel and our phenotypic assay, geno2pheno10% overestimated the frequency of X4-tropic viruses (18% versus 3%). ntPSSM was able to detect one additional X4 virus compared with (ds)Kernel that was confirmed with the phenotypic assay.

Indexed as

Viral TropismGenotypeGenotyping TechniquesHIV-1HIV InfectionsHumansPhenotypeReceptors, HIVVirus CultivationReceptors, HIVCCR5-tropicHIV tropismmaravirocprimary HIV-1 infectionX4-tropic

Identifiers

PMID25608585
PMCPMC4398477
OpenAlexW2062795440

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.