Nucleic acid amplification testing using dried blood spots to confirm the diagnosis of HIV-1 in adults.

Background: The WHO HIV testing algorithm for high prevalence populations recommends the use of three different serologic assays, though this approach may lead to diagnostic misclassification. The study objective was to compare dried blood spot (DBS)-based HIV-1 nucleic acid detection methods to determine their suitability to confirm the diagnosis of HIV-1 in adults generally with suppressed or low-level plasma HIV-1 RNA.

Methods: Four methods were evaluated: Cepheid Xpert HIV-1 Qual Assay (Xpert), Hologic Aptima HIV-1 Quant Dx assay (Aptima), Roche Cobas Ampliprep/Cobas TaqMan HIV-1 test, v.

Retrospective Database Analysis of Liver-Related Clinical Events in Adult and Pediatric Patients with Alpha-1 Antitrypsin Deficiency in the United States.

Background And Aims: Real-world analyses on burden of illness in patients with alpha-1 antitrypsin deficiency (AATD) are limited. We investigated the real-world burden of liver-related clinical events among adult and pediatric patients with AATD in the USA.

Methods: This was a retrospective, observational analysis of administrative claims data from the IQVIA PharMetrics Plus and Ambulatory Electronic Medical Records databases from 2011 to 2022.

Healthcare resource utilization and costs among patients with alpha-1 antitrypsin deficiency with liver and/or lung disease: a longitudinal retrospective study in the USA.

To evaluate all-cause and liver-associated healthcare resource utilization (HCRU) and costs among patients with alpha-1 antitrypsin deficiency (AATD) with liver disease (LD) and/or lung disease (LgD). This was a retrospective analysis of linked administrative claims data from the IQVIA PharMetrics Plus and the IQVIA Ambulatory Electronic Medical Records (AEMR) databases from 1 July 2021 to 31 January 2022. Patients with AATD in the IQVIA PharMetrics Plus database were included with ≥1 inpatient or ≥2 outpatient medical claims ≥90 days apart with a diagnosis of AATD, or with records indicating a protease inhibitor (Pi)*ZZ/Pi*MZ genotype in the IQVIA AEMR database with linkage to IQVIA PharMetrics Plus.

Efficacy of vedolizumab during intravenous induction therapy in ulcerative colitis and Crohn's disease: post hoc analysis of patient-reported outcomes from the VISIBLE 1 and 2 studies.

Background: Vedolizumab is an anti-α4β7 integrin antibody used to treat moderate to severe ulcerative colitis (UC) and Crohn's disease (CD). This post hoc analysis of patient-reported outcomes (PROs) from the VISIBLE 1 (NCT02611830) and 2 (NCT02611817) phase 3 studies evaluated onset of treatment effect on patient-reported symptoms during 6-week vedolizumab induction.

Methods: Patient-reported stool frequency (SF) and rectal bleeding (RB) (UC Mayo score), and SF and abdominal pain (AP) in CD were collected via electronic diary from VISIBLE patients receiving one or more open-label intravenous (IV) vedolizumab induction doses (weeks 0 and 2).

Liver disease epidemiology and burden in patients with alterations in plasma protein metabolism: German retrospective insurance claims analysis.

Background: Alpha-1 antitrypsin deficiency is a rare genetic disease and a leading cause of inherited alterations in plasma protein metabolism (APPM).

Aim: To understand the prevalence, burden and progression of liver disease in patients with APPM including alpha-1 antitrypsin deficiency.

Methods: We conducted a retrospective analysis of anonymized patient-level claims data from a German health insurance provider (AOK PLUS).

Liver disease progression in patients with alpha-1 antitrypsin deficiency and protease inhibitor ZZ genotype with or without lung disease.

Background: Alpha-1 antitrypsin deficiency (AATD) is caused by mutations in SERPINA1, which encodes alpha-1 antitrypsin, a protease inhibitor (Pi). Individuals with AATD and the homozygous Pi*ZZ genotype have variable risk of progressive liver disease but the influence of comorbid lung disease is poorly understood.

Aims: To characterise patients with AATD Pi*ZZ and liver disease (AATD-LD-Pi*ZZ) with or without lung disease and describe liver disease-related clinical events longitudinally.

A multi-center study comparing the analytical sensitivity and clinical concordance of three HIV-1 viral load assays.

Background: HIV-1 viral load assays are essential tools for clinical management of people living with HIV-1.

Objectives And Study Design: We evaluated concordance between three assays: the cobas® HIV-1 test for use on the cobas® 6800 and cobas® 8800 systems (cobas HIV-1); the COBAS® TaqMan® HIV-1 Test, v2.0 for use with the High Pure System and the COBAS® AmpliPrep/COBAS® TaqMan® HIV-1 test, v2.

Classification of HIV-1 virological treatment failure using the Roche cobas plasma separation card on cobas 8800 compared to dried blood spots on Abbott RealTime HIV-1.

Background: Measurement of HIV-1 viral load (VL) is essential for monitoring antiretroviral treatment (ART) efficacy. In remote settings, dried blood spots (DBS) may be used as the specimen type. However, cellular components in DBS not present in the gold standard specimen type, plasma, may result in low specificity i.

HBV-RNA Co-amplification May Influence HBV DNA Viral Load Determination.

Despite effective hepatitis B virus (HBV)-DNA suppression, HBV RNA can circulate in patients receiving nucleoside/nucleotide analogues (NAs). Current assays quantify HBV DNA by either real-time polymerase chain reaction (PCR), which uses DNA polymerase, or transcription-mediated amplification, which uses reverse-transcriptase (RT) and RNA polymerase. We assessed the effect of RT capability on HBV-DNA quantification in samples from three cohorts, including patients with quantified HBV RNA.

Evaluation of the cobas® HCV test for quantifying HCV RNA in dried plasma spots collected using the cobas® Plasma Separation Card.

Objective: This study evaluated the performance of the cobas® hepatitis C virus (HCV) Test for use on the cobas® 6800/8800 Systems for the detection and quantification of HCV RNA collected using the cobas® Plasma Separation Card (PSC) compared with plasma samples.

Methods: Whole EDTA-venous blood was collected from 50 HCV-positive donors and 140 μL from each donor was spotted onto a PSC and stored either frozen or at ambient temperature. These were compared with matched EDTA-plasma samples.

Evaluation of Contamination Risk by the cobas e 602 Serology Module Before Viral Load Testing on the cobas 6800 System.

Background: Diagnosis of HCV, HBV, and HIV involves antibody screening followed by confirmation and/or treatment decision using nucleic acid tests. However, minimal data exist evaluating the risk of nucleic acid cross-contamination on serology devices upstream of molecular testing despite the potential clinical and laboratory workflow advantages of single specimen vial testing for both procedures.

Methods: We conducted a checkerboard study investigating the potential risk of HCV, HBV, and HIV nucleic acid cross-contamination on 480 negative specimens by a serology screening instrument that uses disposable tips for sample transfer, rather than a fixed needle, before molecular testing.

Utility of the new cobas HCV test for viral load monitoring during direct-acting antiviral therapy.

Background: The COBAS AmpliPrep/COBAS TaqMan assay HCV (CAP/CTM) is widely used in clinical routine for HCV testing. Recently, the new cobas HCV test was established for high throughput testing with minimal operator intervention. As different assays may yield different quantitative/qualitative results that possibly impact treatment decisions, the aim of this study was to externally evaluate the cobas HCV test performance in comparison to CAP/CTM in a clinically relevant setting.

Generating timely molecular diagnostic test results: workflow comparison of the cobas® 6800/8800 to Panther.

: Molecular diagnostic tests for HBV, HCV and HIV-1 and other pathogens are widely used for clinical management. Practical issues related to workflow and labor requirements need to be characterized to inform selection of the most appropriate system. : We compared the workflow of two high-throughput systems: cobas 6800 (Roche) and Panther (Hologic), using average mid-size laboratory test volumes for five different assays (HIV-1, HBV, HCV, HPV or TV, and CT/NG).

Analytical performance of four molecular platforms used for HIV-1, HBV and HCV viral load determinations.

: Viral load (VL) quantification is important for the management of HBV, HCV, and HIV-1-infected patients. Several semi- or fully automated systems and assays are available that can be used to measure VL for these and other targets. : We assessed the accuracy, genotype/subtype inclusivity, and precision of four VL assays for three viral targets: cobas 4800 (Roche), cobas 6800 (Roche), Aptima (Hologic) and VERIS (Beckman), using WHO standards, cell culture supernatants and clinical samples.

Multicenter evaluation of the cobas® HIV-1 quantitative nucleic acid test for use on the cobas® 4800 system for the quantification of HIV-1 plasma viral load.

Background And Objectives: Measurement of HIV-1 viral load (VL) is necessary to monitor treatment efficacy in patients receiving antiretroviral therapy. We evaluated the performance of the cobas® HIV-1 quantitative nucleic acid test for use on the cobas® 4800 system ("cobas 4800 HIV-1").

Methods: Limit of detection, linearity, accuracy, precision, and specificity of cobas 4800 HIV-1, COBAS® AmpliPrep/COBAS® Taqman® HIV-1 version 2.

Diagnosis and monitoring of HCV infection using the cobas HCV test for use on the cobas 6800/8800 systems.

Background And Objectives: Accurate, sensitive, and specific tests for detection and monitoring of hepatitis C virus (HCV) RNA concentrations are essential for diagnosis and management of HCV infections. We evaluated the next-generation reverse-transcription real-time PCR test, cobas HCV test for use with the cobas 6800/8800 systems ("cobas HCV") by determining its analytical performance characteristics and clinical utility for the diagnosis and therapeutic monitoring of chronic HCV infections.

Methods: The limit of detection (LOD), linearity, precision, specificity, matrix equivalence of plasma and serum, and quantitative agreement with the COBAS AmpliPrep/COBAS TaqMan HCV Test version 2.

Commutability and concordance of four hepatitis B virus DNA assays in an international multicenter study.

Background: HBV DNA is the most important molecular marker in hepatitis B, used to determine treatment indication and monitoring. Most patients require lifelong hepatitis B virus (HBV) management, thus viral load (VL) monitoring may be performed at different laboratories, with different HBV assays, which may result in different VL results. This multicenter study compares the commutability and concordance of results from four different HBV DNA assays: CAP/CTM HBVv2, HPS/CTM HBVv2 and the new cobas 6800/8800 HBV and cobas 4800 HBV assays.

First identification of a recombinant form of hepatitis C virus in Austrian patients by full-genome next generation sequencing.

Hepatitis C virus (HCV) intergenotypic recombinant forms have been reported for various HCV genotypes/subtypes in several countries worldwide. In a recent study, four patients living in Austria had been identified to be possibly infected with a recombinant HCV strain. To clarify results and determine the point of recombination, full-genome next-generation sequencing using the Illumina MiSeq v2 300 cycle kit (Illumina, San Diego, CA, USA) was performed in the present study.

Evaluation of the COBAS AmpliPrep/COBAS TaqMan HCV Test v2.0 for HCV viral load monitoring using dried blood spot specimens.

This study evaluated the use of dried blood spot (DBS) for HCV viral load quantification using the COBAS AmpliPrep/COBAS Taqman HCV Quantitative Test v2.0 (CAP/CTM HCV v2), and compared two different procedures for preparation of DBS samples with a Specimen Pre-Extraction (SPEX) reagent (either heated [SPEX with SH] for 10min at 56°C on a thermomixer, or incubated for 1h at room temperature [SPEX at RT]) against the standard plasma input. Whole blood specimens from 48 patients with chronic HCV infection and Whatman 903 Protein Saver Cards were used to prepare 35μL DBS.

Advancing the regulatory path on hepatitis B virus treatment and curative research: a stakeholders consultation.

Hepatitis B infection remains a significant disease burden around the world, with an estimated two billion individuals infected and 350 million living with chronic hepatitis B. Current antivirals are efficacious, but require lifelong treatment for the majority of infected individuals. The field is galvanised to improve diagnostics and treatment with the goal to develop shorter, finite treatments leading to viral control after treatment discontinuation.

Multicenter Comparison Study of both Analytical and Clinical Performance across Four Roche Hepatitis C Virus RNA Assays Utilizing Different Platforms.

The efficacy of antiviral treatment for chronic hepatitis C virus (HCV) infection is determined by measuring HCV RNA at specific time points throughout therapy using highly sensitive and accurate HCV RNA assays. This study compared the performances of two recently developed real-time PCR HCV RNA assays, cobas HCV for use on the cobas 6800/8800 systems (cobas 6800/8800 HCV) and cobas HCV for use on the cobas 4800 system (cobas 4800 HCV), with those of two established assays, the Cobas AmpliPrep/Cobas TaqMan HCV quantitative test, version 2 (CAP/CTM v2) and the Cobas TaqMan HCV test, version 2 for use with the High Pure system (HPS/CTM v2). The limits of detection (LODs) and linearity at lower concentrations (5 to 1000 IU/ml) were assessed for cobas 6800/8800 HCV and cobas 4800 HCV using WHO standard traceable panels representing HCV genotypes (GT) 1 to 4.

Evaluation of the new cobas® HCV genotyping test based on real-time PCRs of three different HCV genome regions.

Background: Determination of the hepatitis C virus (HCV) genotype and discrimination between HCV subtypes 1a and 1b is still mandatory prior to anti-HCV treatment initiation. The aim of this study was to evaluate the performance of the recently introduced cobas® HCV GT assay (Roche) and to compare it to two comparator assays.

Methods: The cobas® HCV GT assay is based on primer-specific real-time polymerase chain reaction (PCR).