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Comparison of phenotypic and genotypic tropism determination in triple-class-experienced HIV patients eligible for maraviroc treatment

Linos Vandekerckhove UGent, Chris Verhofstede UGent, Els Demecheleer UGent, Stephane De Wit, Eric Florence, Katrien Fransen, Michel Moutschen, Wendy Mostmans, Kabamba Kabeya and Nicola Mackie, et al. (2011) JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY. 66(2). p.265-272
abstract
Determination of HIV-1 tropism is a pre-requisite to the use of CCR5 antagonists. This study evaluated the potential of population genotypic tropism tests (GTTs) in clinical practice, and the correlation with phenotypic tropism tests (PTTs) in patients accessing routine HIV care. Forty-nine consecutive plasma samples for which an original Trofile(TM) assay was performed were obtained from triple-class-experienced patients in need of a therapy change. Viral tropism was defined as the consensus of three or more tropism calls obtained from the combination of two independent population PTT assays (Trofile Biosciences, San Francisco, CA, USA, and Virco, Beerse, Belgium), population GTTs and GTTs based on ultra-deep sequencing. If no consensus was reached, a clonal PTT was performed in order to finalize the tropism call. This two-step approach allowed the definition of a reference tropism call. According to the reference tropism result, 35/49 samples were CCR5 tropic (R5) (patients eligible for maraviroc treatment) and 14/49 were assigned as non-R5 tropic. The non-R5 samples [patients not eligible for maraviroc treatment according to the FDA/European Medicines Agency (EMEA) label] group included both the CXCR4 (X4) samples and the dual and mixed CCR5/CXCR4 (R5/X4) samples. Compared with Trofile(TM) population PTTs, population GTTs showed a higher sensitivity (97%) and a higher negative predictive value (91%), but almost equal specificity and an equal positive predictive value. In line with recent reports from clinical trial data, our data support the use of population genotypic tropism testing as a tool for tropism determination before the start of maraviroc.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
ANTIRETROVIRAL DRUGS, MYOCARDIAL-INFARCTION, IMMUNODEFICIENCY-VIRUS TYPE-1, phenotypic tests, genotypic tests, HIV-1 tropism, CORECEPTOR USAGE, RISK, RESISTANCE, INHIBITORS, CCR5
journal title
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
J. Antimicrob. Chemother.
volume
66
issue
2
pages
265 - 272
Web of Science type
Article
Web of Science id
000286216300007
JCR category
PHARMACOLOGY & PHARMACY
JCR impact factor
5.068 (2011)
JCR rank
20/259 (2011)
JCR quartile
1 (2011)
ISSN
0305-7453
DOI
10.1093/jac/dkq458
language
English
UGent publication?
yes
classification
A1
copyright statement
I have retained and own the full copyright for this publication
id
1206204
handle
http://hdl.handle.net/1854/LU-1206204
date created
2011-04-11 15:03:38
date last changed
2011-04-18 09:41:48
@article{1206204,
  abstract     = {Determination of HIV-1 tropism is a pre-requisite to the use of CCR5 antagonists. This study evaluated the potential of population genotypic tropism tests (GTTs) in clinical practice, and the correlation with phenotypic tropism tests (PTTs) in patients accessing routine HIV care.
Forty-nine consecutive plasma samples for which an original Trofile(TM) assay was performed were obtained from triple-class-experienced patients in need of a therapy change. Viral tropism was defined as the consensus of three or more tropism calls obtained from the combination of two independent population PTT assays (Trofile Biosciences, San Francisco, CA, USA, and Virco, Beerse, Belgium), population GTTs and GTTs based on ultra-deep sequencing. If no consensus was reached, a clonal PTT was performed in order to finalize the tropism call. This two-step approach allowed the definition of a reference tropism call.
According to the reference tropism result, 35/49 samples were CCR5 tropic (R5) (patients eligible for maraviroc treatment) and 14/49 were assigned as non-R5 tropic. The non-R5 samples [patients not eligible for maraviroc treatment according to the FDA/European Medicines Agency (EMEA) label] group included both the CXCR4 (X4) samples and the dual and mixed CCR5/CXCR4 (R5/X4) samples. Compared with Trofile(TM) population PTTs, population GTTs showed a higher sensitivity (97\%) and a higher negative predictive value (91\%), but almost equal specificity and an equal positive predictive value.
In line with recent reports from clinical trial data, our data support the use of population genotypic tropism testing as a tool for tropism determination before the start of maraviroc.},
  author       = {Vandekerckhove, Linos and Verhofstede, Chris and Demecheleer, Els and De Wit, Stephane and Florence, Eric and Fransen, Katrien and Moutschen, Michel and Mostmans, Wendy and Kabeya, Kabamba and Mackie, Nicola and Plum, Jean and Vaira, Dolores and Van Baelen, Kurt and Vandenbroucke, Ina and Van Eygen, Veerle and Van Marck, Herwig and Vogelaers, Dirk and Geretti, Anna Maria and Stuyver, Lieven J},
  issn         = {0305-7453},
  journal      = {JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY},
  keyword      = {ANTIRETROVIRAL DRUGS,MYOCARDIAL-INFARCTION,IMMUNODEFICIENCY-VIRUS TYPE-1,phenotypic tests,genotypic tests,HIV-1 tropism,CORECEPTOR USAGE,RISK,RESISTANCE,INHIBITORS,CCR5},
  language     = {eng},
  number       = {2},
  pages        = {265--272},
  title        = {Comparison of phenotypic and genotypic tropism determination in triple-class-experienced HIV patients eligible for maraviroc treatment},
  url          = {http://dx.doi.org/10.1093/jac/dkq458},
  volume       = {66},
  year         = {2011},
}

Chicago
Vandekerckhove, Linos, Chris Verhofstede, Els Demecheleer, Stephane De Wit, Eric Florence, Katrien Fransen, Michel Moutschen, et al. 2011. “Comparison of Phenotypic and Genotypic Tropism Determination in Triple-class-experienced HIV Patients Eligible for Maraviroc Treatment.” Journal of Antimicrobial Chemotherapy 66 (2): 265–272.
APA
Vandekerckhove, L., Verhofstede, C., Demecheleer, E., De Wit, S., Florence, E., Fransen, K., Moutschen, M., et al. (2011). Comparison of phenotypic and genotypic tropism determination in triple-class-experienced HIV patients eligible for maraviroc treatment. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 66(2), 265–272.
Vancouver
1.
Vandekerckhove L, Verhofstede C, Demecheleer E, De Wit S, Florence E, Fransen K, et al. Comparison of phenotypic and genotypic tropism determination in triple-class-experienced HIV patients eligible for maraviroc treatment. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY. 2011;66(2):265–72.
MLA
Vandekerckhove, Linos, Chris Verhofstede, Els Demecheleer, et al. “Comparison of Phenotypic and Genotypic Tropism Determination in Triple-class-experienced HIV Patients Eligible for Maraviroc Treatment.” JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY 66.2 (2011): 265–272. Print.