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

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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.
Keywords
ANTIRETROVIRAL DRUGS, MYOCARDIAL-INFARCTION, IMMUNODEFICIENCY-VIRUS TYPE-1, phenotypic tests, genotypic tests, HIV-1 tropism, CORECEPTOR USAGE, RISK, RESISTANCE, INHIBITORS, CCR5

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Citation

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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.
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.
Chicago author-date
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.
Chicago author-date (all authors)
Vandekerckhove, Linos, Chris Verhofstede, Els Demecheleer, Stephane De Wit, Eric Florence, Katrien Fransen, Michel Moutschen, Wendy Mostmans, Kabamba Kabeya, Nicola Mackie, Jean Plum, Dolores Vaira, Kurt Van Baelen, Ina Vandenbroucke, Veerle Van Eygen, Herwig Van Marck, Dirk Vogelaers, Anna Maria Geretti, and Lieven J Stuyver. 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.
IEEE
[1]
L. Vandekerckhove et al., “Comparison of phenotypic and genotypic tropism determination in triple-class-experienced HIV patients eligible for maraviroc treatment,” JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, vol. 66, no. 2, pp. 265–272, 2011.
@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},
  keywords     = {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},
}

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