ObjectivesWe analysed the impact of different parameters on genotypic tropism testing related to clinical outcome prediction in 108 patients on maraviroc (MVC) treatment.Methods87 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.ResultsConcordance 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.ConclusionsProviral 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.
Objective: To evaluate the sensitivity and specificity and to establish the positive and negative predictive values for the tilt test in patients with syncope of unknown origin.Methods: We studied patients with history of dizziness or syncope without any underlying cardiac condition (group A), and another group consisting of healthy volunteers that did not have history of dizziness or syncope (group B). They were initially tilted upright to 70° during 30 min. If the result was negative, 5 mg of sublingual isosorbide dinitrate were given and the patients were tilted upright to 70° again.Results: Of the last 156, a total of 134 patients (45 males and 89 females, mean age of 27.9±14 yrs) had had syncope (Group A), whereas 22 were normal subjects (7 male and 15 females, mean age of 25.4±6.4) that volunteered for the same test. During the panic phase of tilt test syncope occurred in 25 patients (18.7%) of group A, and 5 (22.7%) of group B. 109 were submitted to the drug phase: (81.3%) of group A, and 17 (72.3%) of group B. Sixty patients of group A (55%), and 8 of group B (47%) had a positive test. This increased sensitivity from 18 to 55% and decreased specificity from 77 to 52%.The positive rate of tilt test was 62.8%, the sensitivity 63% and the specificity 40%; the positive predictive value was 0.86, and the negative predictive value 0.15.Conclusions: We consider that either the tilt test is not the ideal to evaluate vaso-vagal syncope, or this is only a physiological condition related to other factors such as anxiety.
Different diagnostic parameters may affect the tropism prediction reliability. The impact of usage of FPR cut-offs<20%, use of viral RNA versus proviral DNA samples, single versus triple amplification, and presence of MVC resistance mutations on tropism prediction at baseline were analysed on 101 patients receiving maraviroc (MVC) and correlated with their clinical outcome. This was a non-interventional, retrospective study. 82 RNA and 54 DNA samples from the 101 patients receiving MVC were obtained. The V3 region was sequenced and the tropism predicted using the geno2pheno[coreceptor] and T-CUP tools with FPR cut-offs of 5%, 7.5%, 10%, 15% and 20%. Additionally, 27/82 RNA and 28/54 DNA samples were analysed in triplicate and 34/82 samples with the ESTA assay. The influence of 16 MVC resistance mutations on clinical outcome was studied. The genotypic susceptibility score (GSS) of the concomitant drugs was mapped to numerical values: susceptible to 1 (or 0.5 for NRTIs), intermediate to 0.5 (0.25 for NRTIs) and resistant to 0. Detection of baseline R5 viruses in RNA (by geno2pheno[coreceptor] and T-CUP) or DNA (by T-CUP) samples correlated with MVC-treatment success. Both tools performed very similarly, with PPVs close to 90%, even with FPR cut-offs as low as 5%. The use of triple amplification did not improve the prediction value but reduced the number of patients elegible for MVC treatment. No influence of the GSS or MVC resistance mutations on the clinical outcome was detected. Genotypic tropism testing from viral RNA and proviral DNA using the geno2pheno[coreceptor] and T-CUP systems is valid to select candidates for MVC treatment. Our data suggest that the use of 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 potent antiretroviral drug
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