ArticleJournal of hepatology2010
Pharmacodynamics of PEG-IFN-alpha-2a in HIV/HCV co-infected patients: implications for treatment outcomes.
Article in Journal of hepatology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Simeprevir with pegylated interferon alfa 2a plus ribavirin for treatment of hepatitis C virus genotype 1 in patients with HIV: a meta-analysis and historical comparison.BMC infectious diseases · 2016Pooled it
- Machine learning for mathematical models of HCV kinetics during antiviral therapy.Mathematical biosciences · 2022Article
- Efficient Methods for Parameter Estimation of Ordinary and Partial Differential Equation Models of Viral Hepatitis Kinetics.Mathematics (Basel, Switzerland) · 2020Article
- A pharmacokinetic/viral kinetic model to evaluate treatment of chronic HCV infection with a non-nucleoside polymerase inhibitor.Antiviral therapy · 2018Article
- In-host modeling.Infectious Disease Modelling · 2017Article
- Therapy of Delta Hepatitis.Cold Spring Harbor perspectives in medicine · 2015Review
- Modelling hepatitis C therapy--predicting effects of treatment.Nature reviews. Gastroenterology & hepatology · 2015Review
- Understanding early serum hepatitis D virus and hepatitis B surface antigen kinetics during pegylated interferon-alpha therapy via mathematical modeling.Hepatology (Baltimore, Md.) · 2014Article
- Viral kinetic modeling: state of the art.Journal of pharmacokinetics and pharmacodynamics · 2014Review
- A hepatitis C virus infection model with time-varying drug effectiveness: solution and analysis.PLoS computational biology · 2014Article
- Natural cytotoxicity receptor-dependent natural killer cytolytic activity directed at hepatitis C Virus (HCV) is associated with liver inflammation, African American race, IL28B genotype, and response to pegylated interferon/ribavirin therapy in chronic HCV infection.The Journal of infectious diseases · 2014Article
- Treatment of hepatitis C with an interferon-based lead-in phase: a perspective from mathematical modelling.Antiviral therapy · 2014Article
- Understanding triphasic HCV decline during treatment in the era of IL28B polymorphisms and direct acting antiviral agents via mathematical modeling.Journal of hepatology · 2013Article
- Analysis of hepatitis C virus decline during treatment with the protease inhibitor danoprevir using a multiscale model.PLoS computational biology · 2013Article
- Understanding silibinin's modes of action against HCV using viral kinetic modeling.Journal of hepatology · 2012Article
- Genetically associated CD16(+)56(-) natural killer cell interferon (IFN)-αR expression regulates signaling and is implicated in IFN-α-induced hepatitis C virus decline.The Journal of infectious diseases · 2012Article
- Mathematical modelling of HCV infection: what can it teach us in the era of direct-acting antiviral agents?Antiviral therapy · 2012Review
- Hepatitis C Viral Kinetics in the Era of Direct Acting Antiviral Agents and IL28B.Current hepatitis reports · 2011Article
- Very early prediction of response to HCV treatment with PEG-IFN-alfa-2a and ribavirin in HIV/HCV-coinfected patients.Journal of viral hepatitis · 2011Article
- Pharmacodynamics of PEG-IFN-[alpha]-2a and HCV response as a function of IL28B polymorphism in HIV/HCV-coinfected patients.Journal of acquired immune deficiency syndromes (1999) · 2011Article
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Authors and funding
7 authors at 4 institutions in 4 countries.
Funding
Abstract
BACKGROUND &
aimsThe pharmacokinetics and pharmacodynamics of pegylated-interferon-alpha-2a (PEG-IFN) have not been described in HCV/HIV co-infected patients. We sought to estimate the pharmacokinetics and pharmacodynamics of PEG-IFN and determine whether these parameters predict treatment outcome.
methodsTwenty-six HCV/human immunodeficiency virus (HIV)-co-infected patients were treated with a 48-week regimen of PEG-IFN (180 microg/week) plus ribavirin (11 mg/kg/day). HCV RNA and PEG-IFN concentrations were obtained from samples collected until week 12. A modeling framework that includes pharmacokinetic and pharmacodynamic parameters was developed.
resultsFive patients discontinued treatment. Seven patients achieved a sustained virological response (SVR). PEG-IFN concentrations at day 8 were similar to steady-state levels (p=0.15) and overall pharmacokinetic parameters were similar in SVRs and non-SVRs. The maximum PEG-IFN effectiveness during the first PEG-IFN dose and the HCV-infected cell loss rate (delta), were significantly higher in SVRs compared to non-SVRs (median 95% vs. 86% [p=0.013], 0.27 vs. 0.11 day(-1) [p=0.006], respectively). Patients infected with HCV genotype 1 had a significantly lower average first-week PEG-IFN effectiveness (median 70% vs. 88% [p=0.043]), however, 4- to 12-week PEG-IFN effectiveness was not significantly different compared to those with genotype 3 (p=0.114). Genotype 1 had a significantly lower delta compared to genotype 3 (median 0.14 vs. 0.23 day(-1) [p=0.021]). The PEG-IFN concentration that decreased HCV production by 50% (EC(50)) was lower in genotype 3 compared to genotype 1 (median 1.3 vs. 3.4 [p=0.034]).
conclusionsBoth the HCV-infected cell loss rate (delta) and the maximum effectiveness of the first dose of PEG-IFN-alpha-2a characterised HIV co-infected patients and were highly predictive of SVR. Further studies are needed to validate these viral kinetic parameters as early on-treatment prognosticators of response in patients with HCV and HIV.
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