Concordance between HIV-1 genotypic coreceptor tropism predictions based on plasma RNA and proviral DNA

C Verhofstede, D Brudney, J Reynaerts, D Vaira, K Fransen, A De Bel, C Seguin-Devaux, S De Wit, L Vandekerckhove, AM Geretti

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

    Abstract

    OBJECTIVE: The aim of the study was to evaluate the use of proviral DNA as a source of viral genetic material for genotypic coreceptor tropism testing (GTT). METHODS: GTT consisted of bulk V3 sequencing followed by geno2pheno interpretation with the interpretative cut-off [false positive rate (FPR)] set at 5 and 10%. GTT was performed for 165 patients with a viral load of >500 HIV-1 RNA copies/mL on simultaneously collected plasma RNA and proviral DNA, and for 126 patients with a viral load of <500 copies/mL on current proviral DNA and pretreatment plasma RNA. Phenotypic tropism testing (PTT) results were available for 142 samples. RESULTS: In the simultaneous RNA/DNA comparison, concordance in prediction was 95.2% (at FPR 10%) and 96.4% (at FPR 5%). Six RNA-R5/DNA-X4 and two RNA-X4/DNA-R5 discordances were observed at an FPR of 10%, and six RNA-R5/DNA-X4 discordances were observed at an FPR of 5%. In the longitudinal RNA/DNA comparison, concordance was 88.1% (at FPR 10%) and 90.5% (at FPR 5%). Eight RNA-X4/DNA-R5 and seven RNA-R5/DNA-X4 discordances were seen at an FPR of 10%, and 10 RNA-R5/DNA-X4 and two RNA-X4/DNA-R5 discordances at an FPR of 5%. The overall concordance of RNA GTT with PTT was 82% (at FPR 10%) and 83% (at FPR 5%). The overall concordance of DNA GTT with PTT was 85% (at both 10 and 5% FPRs). CONCLUSIONS: GTT produced highly concordant tropism predictions for proviral DNA and plasma RNA. GTT on proviral DNA offers a promising approach for tropism prediction in clinical practice, particularly for the assessment of treated patients with low or suppressed viraemia.
    Original languageEnglish
    JournalHIV Medicine
    Volume12
    Issue number9
    Pages (from-to)544-552
    ISSN1464-2662
    DOIs
    Publication statusPublished - 2011

    Keywords

    • B780-tropical-medicine
    • Viral diseases
    • HIV-1
    • AIDS
    • Evaluation
    • Proviral load
    • Genotyping
    • Coreceptors
    • Tropism
    • Viral load
    • Phenotyping
    • Comparison
    • DNA
    • RNA
    • Prediction
    • Laboratory techniques and procedures
    • Belgium
    • UK
    • Europe-West

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