A few direct antiviral agents have been studied in difficult-to-treat patients infected by hepatitis C virus (HCV) genotype 4 (GT4). The efficacy of daclatasvir (DCV), asunaprevir (ASV), pegylated interferon and ribavirin (Peg-IFN/RBV) association was investigated in these patients.
This open-label, single-arm, phase 2 study was conducted in HCV GT4 patients who were null or partial responders to Peg-IFN/RBV. Patients received 24 weeks of DCV (60 mg, once daily), ASV (100 mg, twice daily) and Peg-IFN/RBV. The primary endpoint was sustained virologic response at post-treatment week 12 [sustained virologic response (SVR)12].
Sixty patients were included; 45 (75%) were previous null responders and 27 (45%) had cirrhosis. The most frequent subtypes were GT4a (48%) and GT4d (27%) with 25% of the patients being infected with other subtypes such as 4c, 4r, 4f, 4k, 4j and 4q. The global SVR12 was 95% (90% confidence interval: 90.4–99.6) and 96.3% (90% confidence interval: 87.5–99.5) in cirrhotic patients. All patients achieving SVR12 also achieved SVR24. Previous Peg-IFN/RBV response, IL28b genotype, cirrhosis status or GT4 subtypes did not influence SVR12 rates. Serious adverse events occurred in 13% of the patients, four being cirrhotic and four noncirrhotic. Three (5%) patients stopped HCV therapy prematurely: one because of virologic breakthrough and two because of serious adverse events. Grade 3/4 laboratory abnormalities included leukopenia (33%), neutropenia (27%), thrombocytopenia (4%) and transaminases increase (2%).
Association of DCV plus ASV and peg-IFN/RBV for 24 weeks demonstrated a high rate of SVR12 in HCV GT4-infected prior nonresponders, independently of the cirrhotic status or the GT4 subtype. The safety profile was acceptable, even in cirrhotic patients.
bBiochemistry Department, Avicenne Hospital, Bobigny
dPharmacology Unit, Pontchaillou Hospital
eCIC 1414, Inserm, Rennes
fHepatology Department, Cochin Hospital, Paris
gHepatology Department, Brabois Hospital, Nancy
hHepatology Department, Beaujon Hospital, Clichy
iHepatology Department, St Joseph Hospital, Marseille
jHepatology and Gastroenterology Department, Claude Huriez Hospital, Lille
kHepatology Department, Albert Michallon Hospital, Grenoble
lHepatology Department, Dupuytren Hospital, Limoges
mHepatology Unit, Arnault Tzank Institut, St Laurent du Var
nHepatology Unit, Croix-Rousse Hospital, Lyon
oANRS (France REcherche Nord & Sud Sida-hiv Hépatites)
pHepatology Department, St Antoine Hospital, Paris, France
Correspondence to Dominique Roulot, MD, PhD, Unité d’Hépatologie, Hopital Avicenne, 125 route de Stalingrad, 93009 Bobigny, France Tel: +33 148 955 430; fax: +33 148 955 450; e-mail: firstname.lastname@example.org
Received July 17, 2017
Accepted August 23, 2017