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

(2011) HIV MEDICINE. 12(9). p.544-552
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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.
Keywords
genotypic tropism testing, chemokine (C-C motif) receptor 5 (CCR5) inhibitors, HIV-1 coreceptor, HIV-1 proviral DNA, TREATMENT-EXPERIENCED PATIENTS, ANTIRETROVIRAL THERAPY, BIOINFORMATIC TOOLS, PHENOTYPIC ASSAY, INFECTION, USAGE, POPULATION, MARAVIROC, SAMPLES, R5

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MLA
Verhofstede, Chris, D Brudney, Jacqueline Reynaerts, et al. “Concordance Between HIV-1 Genotypic Coreceptor Tropism Predictions Based on Plasma RNA and Proviral DNA.” HIV MEDICINE 12.9 (2011): 544–552. Print.
APA
Verhofstede, C., Brudney, D., Reynaerts, J., Vaira, D., Fransen, K., De Bel, A., Seguin-Devaux, C., et al. (2011). Concordance between HIV-1 genotypic coreceptor tropism predictions based on plasma RNA and proviral DNA. HIV MEDICINE, 12(9), 544–552.
Chicago author-date
Verhofstede, Chris, D Brudney, Jacqueline Reynaerts, D Vaira, K Fransen, A De Bel, C Seguin-Devaux, S De Wit, Linos Vandekerckhove, and A-M Geretti. 2011. “Concordance Between HIV-1 Genotypic Coreceptor Tropism Predictions Based on Plasma RNA and Proviral DNA.” Hiv Medicine 12 (9): 544–552.
Chicago author-date (all authors)
Verhofstede, Chris, D Brudney, Jacqueline Reynaerts, D Vaira, K Fransen, A De Bel, C Seguin-Devaux, S De Wit, Linos Vandekerckhove, and A-M Geretti. 2011. “Concordance Between HIV-1 Genotypic Coreceptor Tropism Predictions Based on Plasma RNA and Proviral DNA.” Hiv Medicine 12 (9): 544–552.
Vancouver
1.
Verhofstede C, Brudney D, Reynaerts J, Vaira D, Fransen K, De Bel A, et al. Concordance between HIV-1 genotypic coreceptor tropism predictions based on plasma RNA and proviral DNA. HIV MEDICINE. 2011;12(9):544–52.
IEEE
[1]
C. Verhofstede et al., “Concordance between HIV-1 genotypic coreceptor tropism predictions based on plasma RNA and proviral DNA,” HIV MEDICINE, vol. 12, no. 9, pp. 544–552, 2011.
@article{2005447,
  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.},
  author       = {Verhofstede, Chris and Brudney, D and Reynaerts, Jacqueline and Vaira, D and Fransen, K and De Bel, A and Seguin-Devaux, C and De Wit, S and Vandekerckhove, Linos and Geretti, A-M},
  issn         = {1464-2662},
  journal      = {HIV MEDICINE},
  keywords     = {genotypic tropism testing,chemokine (C-C motif) receptor 5 (CCR5) inhibitors,HIV-1 coreceptor,HIV-1 proviral DNA,TREATMENT-EXPERIENCED PATIENTS,ANTIRETROVIRAL THERAPY,BIOINFORMATIC TOOLS,PHENOTYPIC ASSAY,INFECTION,USAGE,POPULATION,MARAVIROC,SAMPLES,R5},
  language     = {eng},
  number       = {9},
  pages        = {544--552},
  title        = {Concordance between HIV-1 genotypic coreceptor tropism predictions based on plasma RNA and proviral DNA},
  url          = {http://dx.doi.org/10.1111/j.1468-1293.2011.00922.x},
  volume       = {12},
  year         = {2011},
}

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