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Parameters Influencing Baseline HIV-1 Genotypic Tropism Testing Related to Clinical Outcome in Patients on Maraviroc.

Sierra S, Dybowski JN, Pironti A, Heider D, Güney L, Thielen A, Reuter S, Esser S, Fätkenheuer G, Lengauer T, Hoffmann D, Pfister H, Jensen B, Kaiser R - PLoS ONE (2015)

Bottom Line: Triple amplification did not improve the prediction value but reduced the number of patients eligible for MVC.FPR cut-offs of 5%-7.5% and single amplification from RNA or DNA would assure a safe administration of MVC without excluding many patients who could benefit from this drug.In addition, the new prediction system T-CUP produced reliable results.

View Article: PubMed Central - PubMed

Affiliation: Institute of Virology, University of Cologne, Cologne, Germany.

ABSTRACT

Objectives: We analysed the impact of different parameters on genotypic tropism testing related to clinical outcome prediction in 108 patients on maraviroc (MVC) treatment.

Methods: 87 RNA and 60 DNA samples were used. The viral tropism was predicted using the geno2pheno[coreceptor] and T-CUP tools with FPR cut-offs ranging from 1%-20%. Additionally, 27 RNA and 28 DNA samples were analysed in triplicate, 43 samples with the ESTA assay and 45 with next-generation sequencing. The influence of the genotypic susceptibility score (GSS) and 16 MVC-resistance mutations on clinical outcome was also studied.

Results: Concordance between single-amplification testing compared to ESTA and to NGS was in the order of 80%. Concordance with NGS was higher at lower FPR cut-offs. Detection of baseline R5 viruses in RNA and DNA samples by all methods significantly correlated with treatment success, even with FPR cut-offs of 3.75%-7.5%. Triple amplification did not improve the prediction value but reduced the number of patients eligible for MVC. No influence of the GSS or MVC-resistance mutations but adherence to treatment, on the clinical outcome was detected.

Conclusions: Proviral DNA is valid to select candidates for MVC treatment. FPR cut-offs of 5%-7.5% and single amplification from RNA or DNA would assure a safe administration of MVC without excluding many patients who could benefit from this drug. In addition, the new prediction system T-CUP produced reliable results.

No MeSH data available.


Related in: MedlinePlus

Baseline characteristics.Panel A: Number of active drugs in the GSS. Panel B: Distribution of the FPR of the baseline viruses: 87 RNA and 60 DNA sequences with single population-based sequencing, and 20 RNA and 18 DNA samples analysed by NGS.
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pone.0125502.g003: Baseline characteristics.Panel A: Number of active drugs in the GSS. Panel B: Distribution of the FPR of the baseline viruses: 87 RNA and 60 DNA sequences with single population-based sequencing, and 20 RNA and 18 DNA samples analysed by NGS.

Mentions: 162 patients were initially enrolled in this study, whereof 108 were finally included in the analysis as at least one baseline V3 sequence and clinical follow-up on MVC treatment were available. 88/108 were male. The median age was 44 years (range 18–81), patients were in median 17 (2–24) years infected with HIV, 9 patients were therapy-naive and 99 patients had undergone a median of 8 (1–25) previous antiretroviral therapies; the 99 therapy-experienced patients had experienced a median of 2.5 (0–25) virological failures. The median VL was 320 copies/mL (40–1265000), whereof 31 patients started the MVC-therapy with a VL≤50, and 77 with detectable viremia [median 829 copies/mL (52–1265000)] (Fig 1). The median CD4 counts was 398 cells/μL (10–1430), [median of 370 (100–1240) for patients starting MVC with VL≤50; median of 370 (10–1250) for patients starting MVC with detectable VL] (Fig 2). The median nadir CD4 counts was 105 cells/μL (1–446) [median of 83 (1–334) for patients starting MVC with VL≤50; median of 111 (7–446) for patients starting MVC with detectable VL]. Clinical follow-up was available for a median of 53 weeks (12–131). The baseline GSS could be calculated for 100/108 (92.6%) of the patients (Fig 3, panel A). It included in median 1.5 active drugs (range 0–3.5).


Parameters Influencing Baseline HIV-1 Genotypic Tropism Testing Related to Clinical Outcome in Patients on Maraviroc.

Sierra S, Dybowski JN, Pironti A, Heider D, Güney L, Thielen A, Reuter S, Esser S, Fätkenheuer G, Lengauer T, Hoffmann D, Pfister H, Jensen B, Kaiser R - PLoS ONE (2015)

Baseline characteristics.Panel A: Number of active drugs in the GSS. Panel B: Distribution of the FPR of the baseline viruses: 87 RNA and 60 DNA sequences with single population-based sequencing, and 20 RNA and 18 DNA samples analysed by NGS.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4430318&req=5

pone.0125502.g003: Baseline characteristics.Panel A: Number of active drugs in the GSS. Panel B: Distribution of the FPR of the baseline viruses: 87 RNA and 60 DNA sequences with single population-based sequencing, and 20 RNA and 18 DNA samples analysed by NGS.
Mentions: 162 patients were initially enrolled in this study, whereof 108 were finally included in the analysis as at least one baseline V3 sequence and clinical follow-up on MVC treatment were available. 88/108 were male. The median age was 44 years (range 18–81), patients were in median 17 (2–24) years infected with HIV, 9 patients were therapy-naive and 99 patients had undergone a median of 8 (1–25) previous antiretroviral therapies; the 99 therapy-experienced patients had experienced a median of 2.5 (0–25) virological failures. The median VL was 320 copies/mL (40–1265000), whereof 31 patients started the MVC-therapy with a VL≤50, and 77 with detectable viremia [median 829 copies/mL (52–1265000)] (Fig 1). The median CD4 counts was 398 cells/μL (10–1430), [median of 370 (100–1240) for patients starting MVC with VL≤50; median of 370 (10–1250) for patients starting MVC with detectable VL] (Fig 2). The median nadir CD4 counts was 105 cells/μL (1–446) [median of 83 (1–334) for patients starting MVC with VL≤50; median of 111 (7–446) for patients starting MVC with detectable VL]. Clinical follow-up was available for a median of 53 weeks (12–131). The baseline GSS could be calculated for 100/108 (92.6%) of the patients (Fig 3, panel A). It included in median 1.5 active drugs (range 0–3.5).

Bottom Line: Triple amplification did not improve the prediction value but reduced the number of patients eligible for MVC.FPR cut-offs of 5%-7.5% and single amplification from RNA or DNA would assure a safe administration of MVC without excluding many patients who could benefit from this drug.In addition, the new prediction system T-CUP produced reliable results.

View Article: PubMed Central - PubMed

Affiliation: Institute of Virology, University of Cologne, Cologne, Germany.

ABSTRACT

Objectives: We analysed the impact of different parameters on genotypic tropism testing related to clinical outcome prediction in 108 patients on maraviroc (MVC) treatment.

Methods: 87 RNA and 60 DNA samples were used. The viral tropism was predicted using the geno2pheno[coreceptor] and T-CUP tools with FPR cut-offs ranging from 1%-20%. Additionally, 27 RNA and 28 DNA samples were analysed in triplicate, 43 samples with the ESTA assay and 45 with next-generation sequencing. The influence of the genotypic susceptibility score (GSS) and 16 MVC-resistance mutations on clinical outcome was also studied.

Results: Concordance between single-amplification testing compared to ESTA and to NGS was in the order of 80%. Concordance with NGS was higher at lower FPR cut-offs. Detection of baseline R5 viruses in RNA and DNA samples by all methods significantly correlated with treatment success, even with FPR cut-offs of 3.75%-7.5%. Triple amplification did not improve the prediction value but reduced the number of patients eligible for MVC. No influence of the GSS or MVC-resistance mutations but adherence to treatment, on the clinical outcome was detected.

Conclusions: Proviral DNA is valid to select candidates for MVC treatment. FPR cut-offs of 5%-7.5% and single amplification from RNA or DNA would assure a safe administration of MVC without excluding many patients who could benefit from this drug. In addition, the new prediction system T-CUP produced reliable results.

No MeSH data available.


Related in: MedlinePlus