A5019355286- Hepatitis C virus research
- Influenza Virus Research Studies
- Hepatitis B Virus Studies
- COVID-19 epidemiological studies
- Liver Disease Diagnosis and Treatment
- Respiratory viral infections research
- HIV/AIDS drug development and treatment
- Viral Infections and Outbreaks Research
- Statistical Methods and Bayesian Inference
- Analytical Chemistry and Chromatography
- Hepatitis Viruses Studies and Epidemiology
- SARS-CoV-2 and COVID-19 Research
- Monoclonal and Polyclonal Antibodies Research
- Bayesian Methods and Mixture Models
- Statistical Methods in Clinical Trials
- Ocular Oncology and Treatments
- HER2/EGFR in Cancer Research
- Inhalation and Respiratory Drug Delivery
- Statistical Distribution Estimation and Applications
- Immune Cell Function and Interaction
- Vascular Malformations Diagnosis and Treatment
- COVID-19 Pandemic Impacts
- Zoonotic diseases and public health
- Mathematical and Theoretical Epidemiology and Ecology Models
- Pneumonia and Respiratory Infections
Roche (Switzerland)
2013-2024
Servier (France)
2005-2007
Institute for International Social Research
2007
Pitié-Salpêtrière Hospital
2006
Sorbonne Université
2006
Inserm
2005
Institut des Hautes Études Scientifiques
2005
Prompt antiviral treatment has the potential to reduce influenza virus transmission close contacts, but rigorous data on magnitude of effects are limited. Animal model indicate that rapid reductions in viral replication after risk transmission. Observational and clinical trial with oseltamivir other neuraminidase inhibitors prompt household index patients seems illness although reported varied widely across studies. In addition, transmitting drug-resistant variants exists all approved...
During infectious disease outbreaks, inference of summary statistics characterizing transmission is essential for planning interventions. An important metric the time-dependent reproduction number ( R t ), which represents expected secondary cases generated by each infected individual over course their period. The value varies during an outbreak due to factors such as varying population immunity and changes interventions, including those that affect individuals' contact networks. While it...
RO7062931 is an N-acetylgalactosamine (GalNAc)-conjugated single-stranded locked nucleic acid oligonucleotide complementary to HBV RNA. GalNAc conjugation targets the liver through asialoglycoprotein receptor (ASGPR). This two-part phase 1 study evaluated safety, pharmacokinetics, and pharmacodynamics of in healthy volunteers patients with chronic hepatitis B (CHB) who were virologically suppressed.Part was a single ascending dose randomized receive (0.1-4.0 mg/kg), or placebo. Part 2...
Epiabm is an open-source software package for epidemiological agent-based modelling, re-implementing the well-known CovidSim model from MRC Centre Global Infectious Disease Analysis at Imperial College London. It has been developed as part of first-year training programme in EPSRC SABS:R3 Doctoral Training University Oxford. The builds age-stratified, spatially heterogeneous population and offers a modular approach to configure run epidemic scenarios, allowing broad scope investigative...
To aid understanding of the effect antiviral treatment on population-level influenza transmission, we used a novel pharmacokinetic–viral kinetic transmission model to test correlation between nasal viral load and infectiousness, evaluate impact that timing with antivirals oseltamivir or baloxavir has transmission. The was run under three candidate profiles whereby infectiousness assumed be proportional titer natural-scale, log-scale, dose–response model. Viral in presence absence were...
ABSTRACT A population drug-disease model was developed to describe the time course of influenza virus with and without oseltamivir treatment investigate opportunities for antiviral combination therapy. Data included viral titers from 208 subjects, across 4 studies, receiving placebo at 20 200 mg twice daily 5 days. 3-compartment mathematical model, comprising target cells infected rate β, free produced p cleared c , δ, implemented in NONMEM an inhibitory Hill function on production ( ),...
Abstract Hepatitis B virus RNA (HBV RNA)–containing particles are encapsidated pre‐genomic (pgRNA) detectable in chronically infected patients addition to virions DNA) that have been suggested as a marker of the treatment efficacy. This makes promising use core protein allosteric modulators, such RG7907, which disrupt nucleocapsid assembly and profoundly reduce HBV RNA. Here, we developed multiscale model extending standard viral dynamic models analyse kinetics DNA 35 treated with RG7907 for...
Background Baloxavir marboxil is an oral, single-dose, cap-dependent endonuclease inhibitor that reduces the duration of influenza symptoms and rapidly stops viral shedding. We developed a susceptible, exposed, infected, recovered (SEIR) model to inform cost-effectiveness (CEM) baloxavir versus oseltamivir or no antiviral treatment in UK.
Abstract Background We conducted a phase II study of oral capecitabine rapidly disintegrating tablets given concurrently with radiation therapy (RT) to assess progression‐free survival (PFS) in children newly diagnosed diffuse intrinsic pontine gliomas (DIPG). Patients and methods Children 3–17 years DIPG were eligible. Capecitabine, 650 mg/m 2 /dose BID (maximum tolerated dose [MTD] concurrent radiation), was administered for 9 weeks starting the first day RT. Following 2‐week break, three...
Background Viral kinetic models have proven useful to characterize treatment effectiveness during HCV therapy with interferon (IFN) or direct-acting antivirals. Methods We use a pharmacokinetic/viral (PK/VK) model describe RNA kinetics danoprevir, protease inhibitor. In Phase I study, danoprevir monotherapy was administered for 14 days in ascending doses ranging from 200 600 mg per day 40 patients of whom 32 were treatment-naive and 8 non-responders prior pegylated IFN-α/ribavirin treatment....
The pharmacokinetics (PK) of RO7049389, a new hepatitis B virus (HBV) core protein allosteric modulator class I, and its active metabolite M5 were studied in fasted fed conditions after single multiple once-a-day twice-a-day doses healthy subjects patients with HBV. nonlinearity the pharmacokinetics, large variability, small sample size per dose arms, higher plasma exposure Asians, heterogeneity patient baseline characteristics seen phase I studies made ethnic sensitivity assessment...
Antiviral treatments against hepatitis B virus (HBV) suppress viral replication but do not eradicate the virus, and need therefore to be taken lifelong avoid relapse. Mathematical models can useful support development of curative anti-HBV agents; however, they mostly focus on short-term HBV DNA data neglect complex host-pathogen interaction. This work aimed characterize effect treatment with lamivudine and/or pegylated interferon (Peg-IFN) in 1,300 patients (hepatitis envelope antigen...
Pharmacologic effects were analysed to determine a dose recommendation for oseltamivir in immunocompromised (IC) adults with influenza.Quantitative clinical pharmacology methods applied data from 160 adult IC patients (aged 18-78 years) two studies (NV20234, 150 patients; NV25118, 10 patients) who received 75-200 mg twice daily up days. An established population-pharmacokinetic (PK) model additional on and carboxylate (OC) clearance described the PK characteristics of versus otherwise...
In this paper, we are interested in estimating parameters entering nonlinear mixed effects models using a likelihood maximization approach. As the accuracy of approximation is likely to govern quality derived estimates both distribution random and fixed parameters, propose methodological approach based on adaptive Gauss Hermite quadrature better approximate function. This work presents improvements that render it accurate computationally efficient problem with, an application mixture models,...
Background Viral kinetic models have proven useful in characterizing treatment effectiveness during HCV therapy with interferon (IFN) as well direct-acting antivirals (DAAs). Methods Here we use a pharmacokinetic/viral (PK/VK) model to describe RNA kinetics setrobuvir, non-nucleosidic inhibitor of the NS5B polymerase enzyme. Using PK data from three studies healthy volunteers and VK Phase I study, where setrobuvir was administered for 3 days, fitted two-compartment first-order absorption...
Background Modelling HCV RNA decline kinetics under therapy has proven useful for characterizing treatment effectiveness. Methods Here we model viral (VK) in 72 patients given a combination of danoprevir, protease inhibitor, and mericitabine, nucleoside polymerase 14 days the INFORM-1 trial. A biphasic VK with time-varying danoprevir mericitabine effectiveness Bliss independence interaction between both drugs provided best fit to data. Results The average final antiviral drug varied 0.998...
Abstract Accurate prediction of COVID-19 cases can optimize clinical trial recruitment, inform mitigation strategies and facilitate rapid medication development. Here we present a country-specific, modified Susceptible, Exposed, Infectious, Removed (SEIR) model SARS-CoV-2 transmission using data from the Johns Hopkins University Dashboard. Inter-country differences in initial exposure, cultural/environmental factors, reporting requirements stringency were incorporated. Asymptomatic patients...
Abstract Clinical Development Phases I‐III Regulatory, Quality, Manufacturing Mericitabine is the prodrug of RO 4995855, a selective inhibitor hepatitis C virus ( HCV ) NS5B polymerase. This study assessed effect renal impairment on 4995855 pharmacokinetics. In this open‐label study, ‐negative volunteers (18–75 years) with normal function NRF : creatinine clearance [ CL CR ] >80 mL/min, n = 10) or stable (mild: 50–80 10; moderate: 30–49 received oral mericitabine 1000 mg twice daily BID...