Multicenter clinical evaluation of alinity m HCV assay performance.

Background: Nucleic acid testing is essential for the detection and quantification of HCV RNA in the diagnosis of HCV infection and treatment monitoring. The Alinity m HCV assay was recently developed by Abbott Molecular for rapid detection and quantification of HCV RNA on the fully automated, continuous, random-access Alinity m analyzer.

Objectives: Our study assessed the performance of the new Alinity m HCV assay for detection and quantification of HCV RNA in a large series of patient samples of various genotypes.

Multicenter clinical comparative evaluation of Alinity m HIV-1 assay performance.

Background: Accurate, rapid detection of HIV-1 RNA is critical for early diagnosis, treatment decision making, and long-term management of HIV-1 infection.

Objective: We evaluated the diagnostic performance of the Alinity m HIV-1 assay, which uses a dual target/dual probe design against highly conserved target regions of the HIV-1 genome and is run on the fully automated Alinity m platform.

Study Design: This was an international, multisite study that compared the diagnostic performance of the Alinity m HIV-1 assay to four commercially available HIV-1 assays routinely used in nine independent clinical laboratories.

Multicenter clinical evaluation of alinity m HBV assay performance.

Background: Accurate molecular methods to detect and quantify hepatitis B virus (HBV) DNA are essential to diagnose chronic infections, guide treatment decisions, assess response to treatment, and determine risk of HBV-related complications. New generations of real-time HBV DNA assay platforms provide results in less than 2-3 h, with continuous loading of specimens and true random-access capability.

Objectives: We examined the clinical performance of the new Alinity m HBV assay, run on the fully automated, continuous, random-access Alinity m platform, to accurately detect and quantify HBV DNA in a large series of patient samples infected with different HBV genotypes frequently encountered in clinical practice.

Multicenter Evaluation of Two Next-Generation HIV-1 Quantitation Assays, Aptima Quant Dx and Cobas 6800, in Comparison to the RealTie HIV-1 Reference Assay.

High accuracy and precision at the lower end of quantification are crucial requirements of a modern HIV viral load (VL) assay, since some clinically relevant thresholds are located at 50 and 200 copies/ml. In this study, we compared the performance of two new fully automated HIV-1 VL assays, Aptima HIV-1 Quant Dx and Cobas HIV-1 (Cobas 6800), with the established RealTie 2000 assay. Assay precision and accuracy were evaluated in a retrospective evaluation out of excess plasma material from four HIV-1+ individuals (subtypes B, C, CRF01_AE, and CRF02_AG).

Long-Term Efficacy, Tolerability, and Renal Safety of Atazanavir/Ritonavir-based Antiretroviral Therapy in a Cohort of Treatment-Naïve Patients with HIV-1 Infection: the REMAIN Study.

Background: Boosted protease inhibitors (PIs), including ritonavir-boosted atazanavir (ATV/r), are a recommended option for the initial treatment of HIV-1 infection based upon clinical trial data; however, long-term real-life clinical data are limited.

Objective: We evaluated the long-term use of ATV/r as a component of antiretroviral combination therapy in the real-life setting in the REMAIN study.

Methods: This was an observational cohort study conducted at sites across Germany, Portugal, and Spain.

Low level HIV viremia is more frequent under protease-inhibitor containing firstline therapy than under NNRTI-regimens.

Introduction: An association of persistent low level viremia (LLV) below 500 copies/mL and a higher risk of therapy failure is still point of controversial discussion. Furthermore, it seems that LLV occurs more frequently in patients with protease-inhibitor regimens than in NNRTI- / or integrase-inhibitor containing therapies. The focus of this work was to assess the prevalence of LLV (50-200 copies/mL) and weak viremia (201-500 copies/mL) in firstline-treated patients according to their therapy regimen.

Dose-intensive chemotherapy including rituximab is highly effective but toxic in human immunodeficiency virus-infected patients with Burkitt lymphoma/leukemia: parallel study of 81 patients.

The results of intensive immunochemotherapy were analyzed in human immunodeficiency virus (HIV)-related Burkitt lymphoma/leukemia (BLL) in two cohorts (Spain and Germany). Alternating cycles of chemotherapy were administered, with dose reductions for patients over 55 years. Eighty percent of patients achieved remission, 11% died during induction, 9% failed and 7% died in remission.

Ambulatory care for HIV-infected patients: differences in outcomes between hospital-based units and private practices: analysis of the RESINA cohort.

Background: The efficacy of highly active antiretroviral therapy (HAART) in the treatment of HIV infection is influenced by factors such as potency of applied drugs, adherence of the patient, and resistance-associated mutations. Up to now, there is insufficient data on the impact of the therapeutic setting.

Methods: Since 2001, the prospective multicenter RESINA study has examined the epidemiology of transmitted HIV drug resistance in Nordrhein-Westfalen, the largest federal state of Germany by population.

Comparison of HIV-1 viral load assay performance in immunological stable patients with low or undetectable viremia.

The goal of antiretroviral therapy is reduction in morbidity and mortality via suppression of human immunodeficiency virus (HIV) viral load (VL) to undetectable levels. VL assay sensitivity has improved over time, but the reproducibility and clinical importance of VL results marginally higher than the limit of detection (LoD) are uncertain. We assessed the reproducibility and concordance of low VL results obtained with the Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 version 2.

Epidemiology of transmitted drug resistance in chronically HIV-infected patients in Germany: the RESINA study 2001-2009.

Objectives: Transmitted HIV drug resistance may impair treatment efficacy of combination antiretroviral therapy (ART). This study describes the epidemiology of transmitted resistance in chronically infected patients.

Methods: In a prospective multicenter trial in Nordrhein-Westfalen, Germany, transmitted drug resistance was determined by genotypic resistance testing in patients on initiation of first-line ART.

Risk factors associated with older age in treatment-naive HIV-positive patients.

Background: Older HIV patients are defined as aged 50 years and older. This group is a growing population in developed countries. In order to improve care for older HIV patients, we intended to gain insight into the specific features of transmission, epidemiology, immunology and antiretroviral treatment (ART) of this population.

Association of ABCC10 polymorphisms with nevirapine plasma concentrations in the German Competence Network for HIV/AIDS.

Background: Nevirapine exhibits marked interpatient variability in pharmacokinetics. CYP2B6 activity and demographic factors are important, but there are a few data on drug transporters for nevirapine. ABCC10 (MRP7) is an efflux transporter highly expressed in liver, intestine, and peripheral blood cells.

Cytochrome P450 2B6 (CYP2B6) and constitutive androstane receptor (CAR) polymorphisms are associated with early discontinuation of efavirenz-containing regimens.

Objectives: Cytochrome P450 2B6 (CYP2B6) is responsible for the metabolic clearance of efavirenz and single nucleotide polymorphisms (SNPs) in the CYP2B6 gene are associated with efavirenz pharmacokinetics. Since the constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) correlate with CYP2B6 in liver, and a CAR polymorphism (rs2307424) and smoking correlate with efavirenz plasma concentrations, we investigated their association with early (<3 months) discontinuation of efavirenz therapy.

Methods: Three hundred and seventy-three patients initiating therapy with an efavirenz-based regimen were included (278 white patients and 95 black patients; 293 male).

The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage?

Background: Although being considered as a rarely observed HIV-1 protease mutation in clinical isolates, the L76V-prevalence increased 1998-2008 in some European countries most likely due to the approval of Lopinavir, Amprenavir and Darunavir which can select L76V. Beside an enhancement of resistance, L76V is also discussed to confer hypersusceptibility to the drugs Atazanavir and Saquinavir which might enable new treatment strategies by trying to take advantage of particular mutations.

Results: Based on a cohort of 47 L76V-positive patients, we examined if there might exist a clinical advantage for L76V-positive patients concerning long-term success of PI-containing regimens in patients with limited therapy options.

Prevalence of key resistance mutations K65R, K103N, and M184V as minority HIV-1 variants in chronically HIV-1 infected, treatment-naïve patients.

Background And Objectives: Minority drug-resistant HIV-1 variants, undetected by conventional genotyping, may impair the outcome of antiretroviral therapy (ART). Thus, we retrospectively analyzed the prevalence of minority drug-resistant HIV-1 variants before ART in chronically HIV-1 infected patients initiating first-line therapy and assessed the impact on clinical outcome in the prospective German Truvada cohort.

Study Design: Samples from 146 antiretroviral treatment-naïve patients were collected between April 2005 and August 2006.

Safety and Efficacy in HIV-1-Infected Patients Treated with Ritonavir-Boosted Saquinavir Mesylate.

OBJECTIVE: To evaluate the safety, tolerability, and efficacy of ritonavir-boosted saquinavir 1000/100 mg twice daily administered as a 500 mg film-coated tablet in HIV-1-infected patients. METHODS: In this open-label, observational, 24-week survey conducted in 8 European countries, eligible HIV-infected participants had been prescribed saquinavir/ritonavir in combination with other nonprotease inhibitor (PI) antiretroviral agents as part of their HIV treatment regimen. The safety (grade 3 or 4 adverse events [AEs]), tolerability (by an investigator-reported subjective rating system), and efficacy (the percentage of participants with <50 and <400 copies/mL HIV RNA and change from baseline in mean CD4+ cell count) were analyzed for the overall study population and 7 subpopulations.

Impact of CYP2B6 983T>C polymorphism on non-nucleoside reverse transcriptase inhibitor plasma concentrations in HIV-infected patients.

Objectives: The aim of this study was to investigate the frequency of CYP2B6 polymorphisms (according to ethnicity) and the influence of heterozygosity and homozygosity on plasma concentrations of efavirenz and nevirapine.

Methods: Following written informed consent, 225 Caucasians and 146 Blacks were recruited from the German Competence Network for HIV/AIDS. Plasma concentrations of efavirenz and nevirapine were assessed by HPLC, and genotyping for 516G>T, 983T>C and 1459T>C polymorphisms in CYP2B6 was conducted by real-time PCR-based allelic discrimination.

Trends of prevalence of primary HIV drug resistance in Germany.

Background: Primary HIV drug resistance (PDR) is associated with poor treatment outcome of first-line highly active antiretroviral therapy (HAART). The aim of the study was to observe the trend of prevalence of PDR between 2001 and 2005.

Methods: In a prospective multicentre study in the state of Nordrhein-Westfalen, Germany, 831 treatment-naive chronically HIV-infected patients underwent genotypic resistance testing.

Comparison of four commercial quantitative HIV-1 assays for viral load monitoring in clinical daily routine.

Background: Quantification of viral load (VL) is standard for monitoring HIV-1 therapy and is crucial before deciding whether to switch or to continue a current antiretroviral regimen.

Methods: We compared the performance of the four most widely used commercial viral-load assays, COBAS Amplicor Monitor v1.5, Versant HIV-1 RNA 3.

Mimotopes selected with antibodies from HIV-1-neutralizing long-term non-progressor plasma.

A promising approach to identify HIV-1 vaccine candidates is to dissect the natural immune response against the virus in persons controlling the infection over decades without any antiviral therapy. Here we focus on a group of such persons, eight long-term non-progressors (LTNP), in which we proved the presence of broadly neutralizing antibodies against HIV-1 in the plasma as very likely cause for their LTNP status. The aim of this study was to identify the epitopes for these neutralizing antibodies, as these should represent immunogens potentially able to elicit neutralizing antibodies upon vaccination.

Adoptive transfer of syngeneic T cells in HIV-1 discordant twins indicates rapid regulation of T-cell homeostasis.

The safety and efficacy of adoptive T-cell transfer (ATT) was tested in the context of viral suppression in syngeneic twins discordant for human immunodeficiency virus type 1 (HIV-1) infection. Human leucocyte antigen-matched T cells of seven HIV-negative twins were obtained by lymphapheresis and immediately transfused into the HIV-infected sibling. Four twins received 12 ATTs each, with a mean of 2.

Virologic therapy response significantly correlates with the number of active drugs as evaluated using a LiPA HIV-1 resistance scoring system.

Background: Resistance testing is increasingly accepted as a tool in guiding the selection of human immunodeficiency virus type 1 (HIV-1) antiretroviral therapy in HIV-1 infected individuals who fail their current regimen.

Objectives: To descriptively compare the correlation between virologic treatment response and results using three genotypic HIV-1 drug resistance interpretation systems: the VERSANT HIV-1 Resistance Assay (LiPA) system and two sequence-based interpretation systems.

Study Design: Specimens from 213 HIV-1-infected subjects, either starting (n=104) or switching to (n=109) a regimen of three or four antiretroviral drugs, were collected retrospectively at baseline and after 3 months of uninterrupted therapy.