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Impact of triplicate testing on HIV genotypic tropism prediction in routine clinical practice

J Symons, Linos Vandekerckhove UGent, R Paredes, Chris Verhofstede UGent, R Bellido, Els Demecheleer UGent, PM van Ham, SFL van Lelyveld, AJ Stam and D van Versendaal, et al. (2012) CLINICAL MICROBIOLOGY AND INFECTION. 18(6). p.606-612
abstract
Guidelines state that the CCR5-inhibitor Maraviroc should be prescribed to patients infected with R5-tropic HIV-1 only. Therefore, viral tropism needs to be assessed phenotypically or genotypically. Preliminary clinical trial data suggest that genotypic analysis in triplicate is associated with improved prediction of virological response by increasing the detection of X4-tropic variants. Our objective was to evaluate the impact of triplicate genotypic analysis on prediction of co-receptor usage in routine clinical practice. Samples from therapy-naive and therapy-experienced patients were collected for routine tropism testing at three European clinical centres. Viral RNA was isolated from plasma and proviral DNA from peripheral blood mononuclear cells. Gp120-V3 was amplified in a triplicate nested RT-PCR procedure and sequenced. Co-receptor usage was predicted using the Geno2Pheno[coreceptor] algorithm and analysed with a false-positive rate (FPR) of 5.75%, 10%, or an FPR of 20% and according to the current European guidelines on the clinical management of HIV-1 tropism testing. A total of 266 sequences were obtained from 101 patient samples. Discordance in tropism prediction for the triplicates was observed in ten samples using an FPR of 10%. Triplicate testing resulted in a 16.7% increase in X4-predicted samples and to reclassification from R5 to X4 tropism for four cases rendering these patients ineligible for Maraviroc treatment. In conclusion, triplicate genotypic tropism testing increases X4 tropism detection in individual cases, which may prove to be pivotal when CCR5-inhibitor therapy is applied.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
POPULATIONS, CORECEPTOR, MARAVIROC, IMMUNODEFICIENCY-VIRUS TYPE-1, tropism, X4-tropic, R5-tropic, maraviroc, HIV-1, genotypic, CXCR4, CCR5, INFECTION, ASSAY
journal title
CLINICAL MICROBIOLOGY AND INFECTION
Clin. Microbiol. Infect.
volume
18
issue
6
pages
606 - 612
Web of Science type
Article
Web of Science id
000303981500024
JCR category
INFECTIOUS DISEASES
JCR impact factor
4.578 (2012)
JCR rank
11/69 (2012)
JCR quartile
1 (2012)
ISSN
1198-743X
DOI
10.1111/j.1469-0691.2011.03631.x
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
2100826
handle
http://hdl.handle.net/1854/LU-2100826
date created
2012-05-08 09:27:04
date last changed
2012-06-07 13:46:56
@article{2100826,
  abstract     = {Guidelines state that the CCR5-inhibitor Maraviroc should be prescribed to patients infected with R5-tropic HIV-1 only. Therefore, viral tropism needs to be assessed phenotypically or genotypically. Preliminary clinical trial data suggest that genotypic analysis in triplicate is associated with improved prediction of virological response by increasing the detection of X4-tropic variants. Our objective was to evaluate the impact of triplicate genotypic analysis on prediction of co-receptor usage in routine clinical practice. Samples from therapy-naive and therapy-experienced patients were collected for routine tropism testing at three European clinical centres. Viral RNA was isolated from plasma and proviral DNA from peripheral blood mononuclear cells. Gp120-V3 was amplified in a triplicate nested RT-PCR procedure and sequenced. Co-receptor usage was predicted using the Geno2Pheno[coreceptor] algorithm and analysed with a false-positive rate (FPR) of 5.75\%, 10\%, or an FPR of 20\% and according to the current European guidelines on the clinical management of HIV-1 tropism testing. A total of 266 sequences were obtained from 101 patient samples. Discordance in tropism prediction for the triplicates was observed in ten samples using an FPR of 10\%. Triplicate testing resulted in a 16.7\% increase in X4-predicted samples and to reclassification from R5 to X4 tropism for four cases rendering these patients ineligible for Maraviroc treatment. In conclusion, triplicate genotypic tropism testing increases X4 tropism detection in individual cases, which may prove to be pivotal when CCR5-inhibitor therapy is applied.},
  author       = {Symons, J and Vandekerckhove, Linos and Paredes, R and Verhofstede, Chris and Bellido, R and Demecheleer, Els and van Ham, PM and van Lelyveld, SFL and Stam, AJ and van Versendaal, D and Nijhuis, M and Wensing, AM},
  issn         = {1198-743X},
  journal      = {CLINICAL MICROBIOLOGY AND INFECTION},
  keyword      = {POPULATIONS,CORECEPTOR,MARAVIROC,IMMUNODEFICIENCY-VIRUS TYPE-1,tropism,X4-tropic,R5-tropic,maraviroc,HIV-1,genotypic,CXCR4,CCR5,INFECTION,ASSAY},
  language     = {eng},
  number       = {6},
  pages        = {606--612},
  title        = {Impact of triplicate testing on HIV genotypic tropism prediction in routine clinical practice},
  url          = {http://dx.doi.org/10.1111/j.1469-0691.2011.03631.x},
  volume       = {18},
  year         = {2012},
}

Chicago
Symons, J, Linos Vandekerckhove, R Paredes, Chris Verhofstede, R Bellido, Els Demecheleer, PM van Ham, et al. 2012. “Impact of Triplicate Testing on HIV Genotypic Tropism Prediction in Routine Clinical Practice.” Clinical Microbiology and Infection 18 (6): 606–612.
APA
Symons, J., Vandekerckhove, L., Paredes, R., Verhofstede, C., Bellido, R., Demecheleer, E., van Ham, P., et al. (2012). Impact of triplicate testing on HIV genotypic tropism prediction in routine clinical practice. CLINICAL MICROBIOLOGY AND INFECTION, 18(6), 606–612.
Vancouver
1.
Symons J, Vandekerckhove L, Paredes R, Verhofstede C, Bellido R, Demecheleer E, et al. Impact of triplicate testing on HIV genotypic tropism prediction in routine clinical practice. CLINICAL MICROBIOLOGY AND INFECTION. 2012;18(6):606–12.
MLA
Symons, J, Linos Vandekerckhove, R Paredes, et al. “Impact of Triplicate Testing on HIV Genotypic Tropism Prediction in Routine Clinical Practice.” CLINICAL MICROBIOLOGY AND INFECTION 18.6 (2012): 606–612. Print.