ArticleScientific reports2017
Sofosbuvir (SOF) Suppresses Ledipasvir (LDV)-resistant Mutants during SOF/LDV Combination Therapy against Genotype 1b Hepatitis C Virus (HCV).
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 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
4 citing papers in PubMed.
- Article
- Treatment of Respiratory Viral Coinfections.Epidemiologia (Basel, Switzerland) · 2022Article
- Chronic Hepatitis B Treatment Strategies Using Polymerase Inhibitor-Based Combination Therapy.Viruses · 2021Review
- Building Optimal Three-Drug Combination Chemotherapy Regimens.Antimicrobial agents and chemotherapy · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
Abstract
Our objective was to identify drug interactions between ledipasvir (LDV) and sofosbuvir (SOF) against a genotype 1b replicon to determine optimal exposures for each agent that will maximize antiviral activity against susceptible and drug-resistant subpopulations. LDV and SOF were evaluated using a fully factorial experimental design in the BelloCell system. Replicon levels and drug-resistant variants were quantified at various times post-therapy for 14 days and a high-dimensional mathematical model was fit to the data. Mutations associated with SOF resistance were not detected; but LDV-resistant mutants were selected and mutant subpopulations increased as exposure intensity increased. Combination therapy was additive for the total replicon population and the LDV-resistant population, but a threshold concentration of 100 ng/ml of SOF must be attained to suppress LDV-resistant subpopulations. These novel findings hold important implications for not only improving therapeutic outcomes, but also maximizing the clinical utility of LDV and SOF combination regimens.
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Registered trials
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