1. Parameters Influencing Baseline HIV-1 Genotypic Tropism Testing Related to Clinical Outcome in Patients on Maraviroc.
- Author
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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, and Kaiser R
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Female, Genes, Viral, Genetic Association Studies, Genotype, HIV Infections virology, HIV-1 drug effects, Humans, Male, Maraviroc, Middle Aged, Treatment Outcome, Young Adult, Cyclohexanes therapeutic use, HIV Fusion Inhibitors therapeutic use, HIV Infections drug therapy, HIV-1 genetics, Triazoles therapeutic use, Viral Tropism genetics
- 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.
- Published
- 2015
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