Quadruple combination therapy using daclatasvir, asunaprevir, pegylated interferon, and ribavirin led to high rates of sustained virologic response (SVR) in treatment-experienced patients with hepatitis C virus genotype 4 (HCV GT4), according to a study published in the European Journal of Gastroenterology & Hepatology.
The ANRS HC32 QUATTRO study was a single-arm, multicenter, nonrandomized, open-label pilot study conducted in 25 clinical centers in France between November 2013 and April 2015 (ClinicalTrials.gov Identifier: NCT02107365).
The main criteria for participants were: at least 18 years of age, chronic HCV GT4 infection, detectable HCV RNA ≥1000 IU/mL at screening, and null or partial response to prior treatment. The proportion of participants presenting with cirrhosis was limited to 50%.
Patients were treated for 24 weeks with daclatasvir 60 mg once daily and asunaprevir 100 mg twice daily systematically associated with subcutaneous pegylated interferon α-2a 180 μg/wk and ribavirin 1000 mg/d (<75 kg) or 1200 mg/d (≥75 kg).
The primary efficacy end point was the percentage of study participants with undetectable HCV RNA 12 weeks after the end of the quadruple combination therapy regimen (SVR12). A secondary efficacy end point was virologic response 24 weeks after end of treatment (SVR24).
Treatment failure was defined as detectable HCV RNA, and even HCV RNA levels below the lower limits of quantification were considered treatment failure. Fifty-seven of 60 patients (95%) achieved SVR12, and all of them achieved SVR24. GT4 subtypes did not affect the response rate. Of the 3 patients who did not achieve SVR12, 2 patients prematurely discontinued treatment due to serious adverse events, and one discontinued treatment due to virologic breakthrough.
Quadruple HCV therapy produced high SVR rates at week 12 (95%) and 24 (100%), indicating the effectiveness of daclatasvir, asunaprevir, pegylated interferon, and ribavirin combination therapy in patients with HCV GT4 who were null or partial responders to previous treatment. The study investigators conclude, “Although this quadruple combination is not recommended in first-line therapy, it can be considered as a valuable second-line therapy, especially in countries where the GT4 is frequent.”
Roulot D, Thibault V, Laforest C, et al; ANRS HC32 QUATTRO Study Group. Efficacy of daclatasvir-based quadruple therapy in nonresponder patients infected by hepatitis C virus genotype 4: the ANRS HC32 QUATTRO study. Eur J Gastroenterol Hepatol. 2018;30(3):302-309.