Trial reportScientific reports2017
The paradox of highly effective sofosbuvir-based combination therapy despite slow viral decline: can we still rely on viral kinetics?
Trial report in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Intrahepatic Viral Kinetics During Direct-Acting Antivirals for Hepatitis C in Human Immunodeficiency Virus Coinfection: The AIDS Clinical Trials Group A5335S Substudy.The Journal of infectious diseases · 2020Trial
- Clinical trial simulation of antiviral drugs.Journal of virology · 2026Review
- Classifying hepatitis B therapies with insights from covalently closed circular DNA dynamics.Virologica Sinica · 2024Review
- Article
- Mathematical modeling of hepatitis C RNA replication, exosome secretion and virus release.PLoS computational biology · 2020Article
- A dynamical motif comprising the interactions between antigens and CD8 T cells may underlie the outcomes of viral infections.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Towards multiscale modeling of the CD8Wiley interdisciplinary reviews. Systems biology and medicine · 2019Review
- Early HCV viral kinetics under DAAs may optimize duration of therapy in patients with compensated cirrhosis.Liver international : official journal of the International Association for the Study of the Liver · 2019Article
- Mutational pathway maps and founder effects define the within-host spectrum of hepatitis C virus mutants resistant to drugs.PLoS pathogens · 2019Article
- Article
- Status of Direct-Acting Antiviral Therapy for Hepatitis C Virus Infection and Remaining Challenges.Gastroenterology · 2019Review
- Modeling how reversal of immune exhaustion elicits cure of chronic hepatitis C after the end of treatment with direct-acting antiviral agents.Immunology and cell biology · 2018Article
- Interferon at the cellular, individual, and population level in hepatitis C virus infection: Its role in the interferon-free treatment era.Immunological reviews · 2018Review
- Modelling how responsiveness to interferon improves interferon-free treatment of hepatitis C virus infection.PLoS computational biology · 2018Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 5 institutions in 2 countries.
Funding
Abstract
High sustained virologic response (SVR) rates have been observed after 6 weeks of anti-HCV treatment using sofosbuvir, ledipasvir and a non-nucleoside polymerase-inhibitor (GS-9669) or a protease-inhibitor (GS-9451) and after 12 weeks with sofosbuvir + ledipasvir. Here we analyze the viral kinetics observed during these treatments to decipher the origin of the rapid cure and to evaluate the possibility of further reducing treatment duration. We found that viral kinetics were surprisingly slow in all treatment groups and could not reproduce the high SVR rates observed. Based on experimental results suggesting that NS5A- or protease-inhibitors can generate non-infectious virus, we incorporated this effect into a mathematical model. We found that to predict observed SVR rates it was necessary to assume that ledipasvir, GS-9669 and GS-9451 rapidly reduce virus infectivity. We predicted with this model that 4 weeks of triple therapy could be sufficient to achieve SVR in patients with undetectable viremia at week 1, but would be suboptimal in general. In conclusion, the rapid cure rate achieved with these combinations is largely disconnected from viral loads measured during treatment. A model assuming that rapid cure is due to a drug effect of generating non-infectious virus could be a basis for future response guided therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.