Correlation between genotypic predictions based on V3 sequences and phenotypic determination of HIV-1 tropism

Raymond, Stéphanie; Delobel, Pierre; Mavigner, Maud; Cazabat, Michelle; Souyris, Corinne; Sandres-Sauné, Karine; Cuzin, Lise; Marchou, B.; Massip, Patrice; Izopet, Jacques

doi:10.1097/qad.0b013e32830ebcd4

Cited by 117 publications

(123 citation statements)

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“…These figures are comparable with previous estimates [22,23,25,29]. Although the overall concordance with PTT was higher with an FPR of 5% than with an FPR of 10%, the difference was very small.…”

Section: Discussionsupporting

confidence: 91%

“…The aim of the present study was to explore the possibility of using proviral DNA for GTT, by comparing large series of both simultaneous plasma RNA and proviral DNA samples from patients with a viral load of 4500 copies/ mL, and current proviral DNA samples and stored plasma RNA samples collected from treated patients with a current viral load of o500 copies/mL. Several algorithms for coreceptor tropism prediction from the envelope V3 sequence have been developed and evaluated [22][23][24][25]. As the aim of the study was not to compare the performances of interpretation systems, analysis was restricted to one algorithm only, geno2pheno (http://coreceptor.bioinf.mpi-inf.mpg.de/index.php), which has demonstrated comparable performance to OTA and ESTA [9].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2011

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ObjectiveThe 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). MethodsGTT 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 4500 HIV-1 RNA copies/mL on simultaneously collected plasma RNA and proviral DNA, and for 126 patients with a viral load of o500 copies/mL on current proviral DNA and pretreatment plasma RNA. Phenotypic tropism testing (PTT) results were available for 142 samples. ResultsIn 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). ConclusionsGTT 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.Keywords: chemokine (C-C motif) receptor 5 (CCR5) inhibitors, genotypic tropism testing, HIV-1 coreceptor, HIV-1 proviral DNA Accepted 25 January 2011Introduction Chemokine (C-C motif) receptor 5 (CCR5) antagonists, members of the class of HIV-1 entry inhibitors, selectively inhibit the replication of CCR5-using (R5) viral strains. Before introducing a CCR5 antagonist as a component of antiretroviral therapy (ART), coreceptor usage, or viral tropism, must be determined to exclude the possibility of the presence of chemokine (C-X-C motif) receptor 4 (CXCR4)-using (X4) strains, as these are associated with poor virological response to the drug [1]. The output of the earliest HIV-1 phenotypic tropism testing (PTT) assay was the formation of syncytia in cultured MT2 cells after virus inoculation. This assay is less well suited for use in routine clinical practice because of inherent difficulties with Correspondence: Prof. Chris Verhofstede, AIDS Reference Laboratory, University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium. Tel: 1 32 9 332 51 61; fax: 1 32 9 332 38 41; e-mail: Chris.verhofstede@ugent.be DOI: 10.1111/j.1468-1293.2011.00922.x HIV Medicine (2011 GTT is based on analysis of the V3-loop sequence of the HIV-1 envelope (env) gene using bioinformatic prediction models to deduce coreceptor usage. GTT has the advantage of being less technically demanding, more rapid and less expensive than PTT, thereby meeting today's need for a fast and...

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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

et al. 2011

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“…The "gold standard" for characterization of HIV-1 tropism is a recombinant virus phenotypic entry assay, but genotypic methods based on the V3 sequence could be easier. We have previously shown that the V3 genotype accurately predicts the phenotype of HIV-1 coreceptor usage for subtype B viruses (5,13). However, the V3-based genotypic algorithms could be unsuitable for predicting the tropism of non-B viruses because they were built using data sets of genotype-phenotype correlations from subtype B viruses (9).…”

mentioning

confidence: 99%

“…Two separate PCR amplifications were performed in parallel for each patient and pooled to prevent sampling bias of the assessed virus population. The V3 region from the env PCR product was bulk sequenced, blinded to the phenotype, as previously described (13). Bulk sequencing allows the detection of minor variants when present at a frequency of at least 20% in the viral population.…”

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confidence: 99%

Genotypic Prediction of Human Immunodeficiency Virus Type 1 CRF02-AG Tropism

et al. 2009

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We assessed the performance of genotypic algorithms for predicting the tropism of human immunodeficiency virus type 1 coreceptor usage in 52 patients infected with the CRF02-AG subtype. The combined criteria of the 11/25 and net charge rules accurately detected CXCR4-using CRF02-AG viruses, whereas the Geno2pheno tool lacked sensitivity and the position-specific scoring matrix (PSSM) tool WebPSSM lacked specificity.

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“…In other studies, higher sensitivities could be found for the same genotypic algorithms (Chueca et al, 2009;Raymond et al, 2008). Geno2pheno presented sensitivities of 88-93.7% and specificity of 87%, and PSSM with sensitivities of 77% and specificity of 94%.…”

Section: Impact Of Hiv-1 Diversity In the Performance Of Genotypic Anmentioning

confidence: 65%

HIV-1 Diversity and Its Implications in Diagnosis, Transmission, Disease Progression, and Antiretroviral Therapy

Bártolo¹,

Taveira²

2012

Genetic Diversity in Microorganisms

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Correlation between genotypic predictions based on V3 sequences and phenotypic determination of HIV-1 tropism

Cited by 117 publications

References 19 publications

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

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

Genotypic Prediction of Human Immunodeficiency Virus Type 1 CRF02-AG Tropism

HIV-1 Diversity and Its Implications in Diagnosis, Transmission, Disease Progression, and Antiretroviral Therapy

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