Search results for "Protease Inhibitor"
showing 10 items of 125 documents
Cost-effectiveness of boceprevir or telaprevir for untreated patients with genotype 1 chronic hepatitis C.
2012
BACKGROUND AND AIMS: Randomized controlled trials (RCTs) show that triple therapy (TT) with peginterferon alfa, ribavirin and boceprevir (BOC) or telaprevir (TVR) is more effective than peginterferon-ribavirin dual therapy (DT) in the treatment of previously untreated patients with genotype 1 (G1) chronic hepatitis C (CHC). We assess the cost-effectiveness of TT compared to DT in the treatment of untreated patients with G1 CHC. METHODS: We created a Markov Decision Model to evaluate, in an untreated Caucasian patients aged 50 years, weight 70 kg, with G1 CHC and Metavir F2 liver fibrosis score, for a time horizon of twenty years, the cost-effectiveness of the following 5 competing strategie…
Cost effectiveness of boceprevir or telaprevir for previously treated patients with genotype 1 chronic hepatitis C.
2013
Background & Aims Randomised controlled trials (RCTs) show that triple therapy (TT) with peginterferon alfa, ribavirin, and boceprevir (BOC) or telaprevir (TVR) is more effective than peginterferon-ribavirin dual therapy (DT) in the treatment of genotype 1 (G1) chronic hepatitis C (CHC) patients with previous relapse (RR), partial response (PAR), and null-response (NR). We assess the cost-effectiveness of TT compared to no therapy in the treatment of patients previously treated with G1 CHC. Methods The available published literature provided the data source. The target population was made up of previously treated Caucasian patients with G1 CHC and these were evaluated over a lifetime horizo…
Effects of Smoking on Pegylated Interferon alpha 2a and First Generation Protease Inhibitor-based Antiviral Therapy in Naïve Patients Infected with H…
2016

 
 
 
 
 
 Background & Aims: Smoking has multiple effects on factors influencing hepatitis C and antiviral therapy, including lipid metabolism, fibrosis, platelet count and adherence aspects. The aim of this analysis was to determine the impact of smoking on hepatitis C virus antiviral therapy.
 Methods: Data of two cohorts of an observational multicenter study including therapy-naïve patients infected with genotype 1 hepatitis C virus (HCV) treated with dual antiviral therapy (n=7,796) with pegylated interferon alpha 2a in combination with ribavirin, or triple antiviral therapy (n=1,122) containing telaprevir or boceprevir, were analysed.
 Resu…
Genotypic resistance profiles associated with virological failure to darunavir-containing regimens: a cross-sectional analysis.
2012
Introduction: This study aimed at defining protease (PR) resistance mutations associated with darunavir (DRV) failure and PR resistance evolution at DRV failure in a large database of treatment-experienced human immunodeficiency virus (HIV) patients. Results: Overall, 1,104 patients were included: 118 (10.7%) failed at a median observation time of 16 months. The mean number of PR mutations at baseline was 2.7, but it was higher in patients who subsequently failed DRV. In addition, the number of PR mutations increased at failure. The increase in the mean number of mutations was completely related to mutations considered to be associated with DRV resistance following the indications of the ma…
Anemia during treatment with peginterferon Alfa-2b/ribavirin and boceprevir: Analysis from the serine protease inhibitor therapy 2 (SPRINT-2) trial
2013
International audience; Boceprevir (BOC) added to peginterferon alfa-2b (PegIFN) and ribavirin (RBV) significantly increases sustained virologic response (SVR) rates over PegIFN/RBV alone in previously untreated adults with chronic hepatitis C genotype 1. We evaluate the relationship of incident anemia with triple therapy. A total of 1,097 patients received a 4-week lead-in of PegIFN/RBV followed by: (1) placebo plus PegIFN/RBV for 44 weeks (PR48); (2) BOC plus PegIFN/RBV using response-guided therapy (BOC/RGT); and (3) BOC plus PegIFN/RBV for 44 weeks (BOC/PR48). The management of anemia (hemoglobin [Hb]<10 g/dL) included RBV dose reduction and/or erythropoietin (EPO) use. A total of 1,080…
Coagulation factors and proteinase inhibitors in the plasma of children with acute lymphoblastic leukoses. Behaviour before and during treatment acco…
1984
The thrombocyte count, the factor XIII (F XIII) activity, the concentration of fibrinogen (F I), prothrombin (F II), fibronectin (CIG), albumin and the proteinase inhibitors antithrombin III (AT III), alpha 2-macroglobulin (A2M), alpha 1-antitrypsin (A1A) and Cl-esterase inactivator (Cl-INA) were determined in ten children with acute lymphoblastic leukaemia (ALL). Changes due to the disease and to therapy were observed. Before the start of treatment the patients had thrombocytopenia secondary to the disease, and the proteinase inhibitors--especially Cl-INA and A1A--were raised. During the induction phase the thrombocyte count rose but there was also a marked increase in the concentration of…
Structure-Guided, Single-Point Modifications in the Phosphinic Dipeptide Structure Yield Highly Potent and Selective Inhibitors of Neutral Aminopepti…
2014
Seven crystal structures of alanyl aminopeptidase from Neisseria meningitides (the etiological agent of meningitis, NmAPN) complexed with organophosphorus compounds were resolved to determine the optimal inhibitor–enzyme interactions. The enantiomeric phosphonic acid analogs of Leu and hPhe, which correspond to the P1 amino acid residues of well-processed substrates, were used to assess the impact of the absolute configuration and the stereospecific hydrogen bond network formed between the aminophosphonate polar head and the active site residues on the binding affinity. For the hPhe analog, an imperfect stereochemical complementarity could be overcome by incorporating an appropriate P1 side…
Functional and structural insights into astacin metallopeptidases
2012
The astacins are a family of multi-domain metallopeptidases with manifold functions in metabolism. They are either secreted or membrane-anchored and are regulated by being synthesized as inactive zymogens and also by colocalizing protein inhibitors. The distinct family members consist of N-terminal signal peptides and pro-segments, zincdependent catalytic domains, further downstream extracellular domains, transmembrane anchors, and cytosolic domains. The catalytic domains of four astacins and the zymogen of one of these have been structurally characterized and shown to comprise compact ~200-residue zinc-dependent moieties divided into an N-terminal and a C-terminal sub-domain by an active-s…
Effect of antiretroviral protease inhibitors alone, and in combination with paromomycin, on the excystation, invasion and in vitro development of Cry…
2003
With the spread of the human immunodeficiency virus in the early 1980s, cryptosporidiosis was regarded as an AIDS-defining disease. As an opportunistic pathogen, the intestinal parasite Cryptosporidium parvum became an important cause of chronic diarrhoea, leading to high morbidity and mortality in immunocompromised patients. To date, no effective chemotherapy is available. With the introduction of protease inhibitors (PIs) in highly active antiretroviral therapy (HAART), the incidence of cryptosporidiosis in AIDS patients has declined substantially in western countries. We have therefore tested the effect of five PIs used in HAART on the excystation, invasion and development of the parasit…