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4 results on '"genotypic tropism testing"'

1. Performance of Genotypic Tools for Prediction of Tropism in HIV-1 Subtype C V3 Loop Sequences.

Author

Gupta, Soham, Neogi, Ujjwal, Srinivasa, Hiresave, and Shet, anita

Subjects
*GENOTYPES, *VIRAL tropism, *PREDICTION theory, *NUCLEOTIDE sequence, *MACHINE learning, *GENETIC algorithms
Abstract

Currently, there is no consensus on the genotypic tools to be used for tropism analysis in HIV-1 subtype C strains. Thus, the aim of the study was to evaluate the performance of the different V3 loop-based genotypic algorithms available. We compiled a dataset of 645 HIV-1 subtype C V3 loop sequences of known coreceptor phenotypes (531 R5-tropic/non-syncytium-inducing and 114 X4-tropic/R5X4-tropic/syncytium-inducing sequences) from the Los Alamos database (http://www.hiv.lanl.gov/) and previously published literature. Coreceptor usage was predicted based on this dataset using different software-based machine-learning algorithms as well as simple classical rules. All the sophisticated machine-learning methods showed a good concordance of above 85%. Geno2Pheno (false-positive rate cutoff of 5-15%) and CoRSeqV3-C were found to have a high predicting capability in determining both HIV-1 subtype C X4-tropic and R5-tropic strains. The current sophisticated genotypic tropism tools based on V3 loop perform well for tropism prediction in HIV-1 subtype C strains and can be used in clinical settings. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Published
2015
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2. High concordance of genotypic coreceptor prediction in plasma-viral RNA and proviral DNA of HIV-1 subtype C: implications for use of whole blood DNA in resource-limited settings.

Author

Gupta, Soham, Neogi, Ujjwal, Srinivasa, Hiresave, and Shet, Anita

Subjects
*TROPISMS, *HIV, *CHEMICAL inhibitors, *VIREMIA, *HIV-positive persons
Abstract

Objectives Genotypic tropism testing (GTT) of HIV is increasingly used prior to the initiation of CCR5 antagonist therapy in HIV-infected individuals. Normally performed on plasma-derived virus, the test is challenging when performed in patients with suppressed viraemia. We aimed to evaluate the performance of cell-associated proviral DNA against plasma-derived viral RNA as the genetic material for GTT in an Indian clinical setting. Methods From 52 HIV-1-infected individuals, the env V3 region was successfully amplified and sequenced from both proviral DNA and plasma RNA paired samples having a viral load >2500 copies/mL (n = 42) and from proviral DNA only in 10 antiretroviral therapy (ART)-experienced patients with a viral load <500 copies/mL. GTT was performed using the Geno2Pheno algorithm with the interpretative false positive rate (FPR) cut-off of 10%. Results Among paired samples, 40 of 42 patients harboured subtype C strains. Plasma RNA tropism prediction revealed X4 tropism in 4 of 42 (9.5%). A high concordance of 97.6% in tropism prediction was noted in simultaneous RNA/DNA samples (38 R5 and 3 X4). Discordance was observed in one sample showing R5 tropism in proviral DNA and X4 tropism in plasma RNA. Comparison of Geno2Pheno FPRs in both the plasma and proviral compartments showed good correlation (overall, r = 0.87; ART-naive patients, r = 0.79; ART-failing patients, r = 0.97). GTT was successfully performed in all 10 whole blood DNA samples having a viral load <500 copies/mL, all showing R5 tropism. Conclusions High concordance in tropism prediction from proviral DNA and plasma-viral RNA suggests that prediction of viral tropism using proviral DNA is accurate and feasible in resource-limited clinical settings, particularly in patients with low or suppressed viraemia. [ABSTRACT FROM PUBLISHER]

Published
2013
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3. Concordance between HIV-1 genotypic coreceptor tropism predictions based on plasma RNA and proviral DNA

Author

Verhofstede, Chris, Brudney, Daniel, Reynaerts, Jacqueline, Vaira, Dolores, Fransen, Katrien, De Bel, Annelies, Seguin-Devaux, Carole, De Wit, Stéphane, Vandekerckhove, Linos, Geretti, Anna Maria, Verhofstede, Chris, Brudney, Daniel, Reynaerts, Jacqueline, Vaira, Dolores, Fransen, Katrien, De Bel, Annelies, Seguin-Devaux, Carole, De Wit, Stéphane, Vandekerckhove, Linos, and Geretti, Anna Maria

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 <500copies/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. © 2011 British HIV Association., SCOPUS: ar.j, FLWIN, info:eu-repo/semantics/published

Published
2011

4. Performance of genotypic tropism testing in clinical practice using the enhanced sensitivity version of Trofile as reference assay: Results from the OSCAR Study Group

Author

Svicher V, D'Arrigo R, Alteri C, Andreoni M, Angarano G, Antinori A, Antonelli G, Bagnarelli P, Baldanti F, Bertoli A, Boeri E, Bruzzone B, Callegaro AP, Cammarota R, Canducci F, Ceccherini Silberstein F, Clementi M, Monforte AD, De Luca A, Di Biagio A, Di Gianbenedetto S, Di Perri G, Di Pietro M, Fabeni L, Fadda G, Galli M, Gennari W, Ghisetti V, Giacometti A, Gori A, Leoncini F, Maggiolo F, Maserati R, Mazzotta F, Micheli V, Meini G, Monno L, Mussini C, Nozza S, Paolucci S, Parisi S, Pecorari M, Pizzi D, Quirino T, Rizzardini G, Santangelo R, Soria A, Stazi F, Sterrantino G, Turriziani O, Viscoli C, Vullo V, Lazzarin A, Perno CF, OSCAR Study Group, BORDERI, MARCO, BON, ISABELLA, RE, MARIA CARLA, Svicher V, D'Arrigo R, Alteri C, Andreoni M, Angarano G, Antinori A, Antonelli G, Bagnarelli P, Baldanti F, Bertoli A, Borderi M, Boeri E, Bonn I, Bruzzone B, Callegaro AP, Cammarota R, Canducci F, Ceccherini-Silberstein F, Clementi M, Monforte AD, De Luca A, Di Biagio A, Di Gianbenedetto S, Di Perri G, Di Pietro M, Fabeni L, Fadda G, Galli M, Gennari W, Ghisetti V, Giacometti A, Gori A, Leoncini F, Maggiolo F, Maserati R, Mazzotta F, Micheli V, Meini G, Monno L, Mussini C, Nozza S, Paolucci S, Parisi S, Pecorari M, Pizzi D, Quirino T, Re MC, Rizzardini G, Santangelo R, Soria A, Stazi F, Sterrantino G, Turriziani O, Viscoli C, Vullo V, Lazzarin A, Perno CF, and OSCAR Study Group.

Subjects
Male, Protein Structure, trafile, Receptors, CCR5, Genotype, Settore MED/17 - Malattie Infettive, HIV, viral load, AIDS, hiv, HIV Infections, HIV Envelope Protein gp120, v3 loop, Receptors, Humans, Viral Tropism, Protein Structure, Tertiary, HIV-1, Female, Receptors, Virus, tropism, virus diseases, genotypic tropism testing, OSCAR Study Group, Settore MED/07 - Microbiologia e Microbiologia Clinica, Virus, genotypic tropism, CCR5 Receptor Antagonists, CCR5, Tertiary
Abstract

Objective: The goal of the OSCAR programme is to evaluate the performances of genotypic HIV-1 tropism testing in clinical practice using the enhanced sensitivity version of Trafile (ESTA) as reference-assay. Methods: HIV-1 coreceptor-usage was assessed using plasma samples from 406 HIV-1 infected patients by ESTA and by gp120 V3 population-sequencing followed by Geno2pheno (set at a False Positive Rate [FPR] of 10% and 5%). Results: ESTA was successful in 365 (89.9%) samples indicating R5 in 254 (69.6%), and DM/X4 in 111 (30.4% of samples (104 [28.5%] DM and 7 [1.9%] X4). Genotypic-testing successfully assessed viral tropism for all 406 samples, including the 41 with undetermined result by ESTA. Genotypic-tropism testing at a FPR of 5% and 10% was 81.1% and 78.4% concordant with ESTA, respectively. Despite a sensitivity of 48.7% and 55.9% at a FPR of 5% and 10%, respectively, a high concordance (specificity: 95.3% for FPR of 5% and 88.2% for FPR of 10%) between genotypic-tropism testing and ESTA was reached in the detection of R5-tropic viruses. Conclusion: Our results are in line with other European studies, and support the routine use of genotypic tropism testing in clinical-settings for monitoring of HIV-1 infected patients candidate to or failing CCR5-antagonists.

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