TY  - JOUR
A1  - Dölken, Lars
A1  - Stich, August
A1  - Spinner, Christoph D.
T1  - Remdesivir for Early COVID-19 Treatment of High-Risk Individuals Prior to or at Early Disease Onset — Lessons Learned
JF  - Viruses
N2  - After more than one year of the COVID-19 pandemic, antiviral treatment options against SARS-CoV-2 are still severely limited. High hopes that had initially been placed on antiviral drugs like remdesivir have so far not been fulfilled. While individual case reports provide striking evidence for the clinical efficacy of remdesivir in the right clinical settings, major trials failed to demonstrate this. Here, we highlight and discuss the key findings of these studies and underlying reasons for their failure. We elaborate on how such shortcomings should be prevented in future clinical trials and pandemics. We suggest in conclusion that any novel antiviral agent that enters human trials should first be tested in a post-exposure setting to provide rapid and solid evidence for its clinical efficacy before initiating further time-consuming and costly clinical trials for more advanced disease. In the COVID-19 pandemic this might have established remdesivir early on as an efficient antiviral agent at a more suitable disease stage which would have saved many lives, in particular in large outbreaks within residential care homes.
KW  - COVID-19
KW  - SARS-CoV-2
KW  - antiviral treatment
KW  - remdesivir
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239648
SN  - 1999-4915
VL  - 13
IS  - 6
ER  - 
TY  - JOUR
A1  - Kuntzen, Thomas
A1  - Kuhn, Sereina
A1  - Kuntzen, Daniela
A1  - Seifert, Burkhardt
A1  - Müllhaupt, Beat
A1  - Geier, Andreas
T1  - Influence of Ribavirin Serum Levels on Outcome of Antiviral Treatment and Anemia in Hepatitis C Virus Infection
JF  - PLoS ONE
N2  - Background
Ribavirin blood levels vary considerably between patients with standard weight-based dosing. Their impact on sustained virological response (SVR) with pegylated interferon and ribavirin is controversial, but has mostly been studied before the IL28b gene polymorphism as a possible confounder was discovered.

Methods
The impact of serum ribavirin trough levels at week 4, at the end of treatment and of mean levels across the entire antiviral treatment with pegylated interferon and ribavirin on relapse, SVR rates and anemia was retrospectively studied by univariate and multivariable logistic regression analyses in 214 patients with HCV genotype 1–4 infection, including 88 patients with available IL28b genotyping.

Results
Mean ribavirin levels varied between 0.68–5.65 mg/l and significantly differed between patients with or without SVR. By multivariable regression including age, sex, HCV viral load, HCV genotype, liver fibrosis stage, prior treatments, immunosuppression and IL28b genotype, ribavirin levels consistently displayed significant influence on SVR and relapse without indication for a specific importance of higher concentrations early or late in the treatment course. Although hemoglobin decline was on average more pronounced in patients with higher ribavirin levels, hemoglobin remained relatively stable in a significant proportion of these, indicating that ribavirin levels alone are insufficient to predict anemia.

Conclusion
While data are scarce to draw conclusions applicable for modern DAA therapies, these results support ribavirin treatment based on serum levels instead of purely weight-based dosing in combination with pegylated interferon.
KW  - ribavirin serum levels
KW  - antiviral treatment
KW  - anemia
KW  - Hepatitis C
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166888
VL  - 11
IS  - 7
ER  -