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

L Vandekerckhove, C Verhofstede, E Demecheleer, S De Wit, E Florence, K Fransen, M Moutschen, W Mostmans, K Kabeya, N Mackie, J Plum, D Vaira, K Van Baelen, I Vandenbroucke, V Van Eygen, H Van Marck, D Vogelaers, AM Geretti, LJ Stuyver

    Research output: Contribution to journalA1: Web of Science-article

    Abstract

    Background 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. Methods 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. Results 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. Conclusions 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.
    Original languageEnglish
    JournalJournal of Antimicrobial Chemotherapy
    Volume66
    Issue number2
    Pages (from-to)265-272
    Number of pages8
    ISSN0305-7453
    DOIs
    Publication statusPublished - 2011

    Keywords

    • B780-tropical-medicine
    • Viral diseases
    • HIV-1
    • AIDS
    • HAART
    • Antiretrovirals
    • Maraviroc
    • Tropism
    • Genotyping
    • Phenotyping
    • Assays
    • Sequencing
    • CXCR4
    • CCR5
    • Laboratory techniques and procedures

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