European Ravs Database: Frequency and Characteristics of Ravs in Treatment-Naïve and DAA-Experienced Patients

Real‐world use, effectiveness and safety of anti‐viral treatment in chronic hepatitis C genotype 3 infection

“…Our present data are similar to the data of the UK early access program (EAP), which showed a SVR of only 61% for 12 weeks LDV/SOF±RBV in patients with advanced cirrhosis . Interestingly, sequence analysis of GT3‐infected patients with failure to LDV/SOF‐based therapy from a large European Resistance Databank showed no selection of NS5A RAS . This indicates a low anti‐viral activity of LDV against GT3 isolates.…”

“…26 Interestingly, sequence analysis of GT3-infected patients with failure to LDV/SOF-based therapy from a large European Resistance Databank showed no selection of NS5A RAS. 27 This indicates a low anti-viral activity of LDV against GT3 isolates. However, patients treated according to the label for 24 weeks with LDV/SOF+RBV showed a SVR >90% in difficult-to-treat patients, which may be explained by some additional efficacy of the administration of LDV, if given for a longer period despite a low anti-viral activity against GT3.…”

Treatment of Hepatitis C virus infection in Italy: A consensus report from an expert panel

“…Resistance analysis in genotype 2 patients failing to achieve the SVR to NS5B-containing regimens found no NS5B RAV development, as expected by the low replicative fitness exhibited by viral strains carrying amminoacidic changes in the NS5B polymerase domain [28]. In addition, presence of NS5A RAV at baseline seems not to affect efficacy of SOF + DCV regimen in genotype 2 patients, as demonstrated by subanalysis of DCV clinical trials [19].…”

S3-Leitlinie „Prophylaxe, Diagnostik und Therapie der Hepatitis-C-Virus (HCV) -Infektion“

“…Bei einem Therapieversagen können Resistenz-assoziierte Varianten (RAVs) gegenüber den eingesetzten DAAs bei 80 -90 % der Patienten nachgewiesen werden [315,320,330,340,356,376]. Die Dauer der Nachweisbarkeit von viralen Resistenzen mit einer populationsbasierten Sequenzierung bei Patienten mit Therapieversagen reicht in den meisten Fällen bei Resistenzen gegenüber Protease-Inhibitoren über wenige Monate bis zu einem Jahr [356,377,378]. Nach Einsatz eines nicht-nukleosidischen NS5B-Inhibitors (Dasabuvir) sind RAVs in ca.…”

“…RAVs gegenüber dem nukleosidischen Polymerase-Inhibitor Sofosbuvir wurden bisher nur in wenigen Einzelfällen nachgewiesen und scheinen eine sehr kurze Halbwertszeit von wenigen Wochen aufzuweisen [380 -382]. Bei einem Therapieversagen auf einen NS5A-Inhibitor persistieren die selektionierten RAVs dagegen in der überwiegenden Mehrzahl der Fälle über Jahre [356,383].…”