Direct-acting antivirals with ribavirin safe, effective in certain genotype 1 HCV patients
Retreatment with ledipasvir (LDV) and sofosbuvir (SOF) with add-on ribavirin (RBV) appears to be effective and well tolerated in genotype 1 hepatitis C virus (HCV)-infected patients who have failed to respond to daclatasvir (DCV)/asunaprevir (ASV) combination therapy, according to a study.
The multicentre, prospective study included 15 patients who were retreated with SOF, LDV and RBV for 12 weeks. All patients underwent physical examinations and blood tests at baseline, during treatment and after therapy.
Additionally, NS3/NS5A and NS5B resistance-associated variants (RAVs) were evaluated at baseline and relapse. Resulting data revealed RAVs in NS3 D168A/V/T/E in 11 patients (73.3 percent), NS5A L31I/M/F/V plus Y93H in 13 patients (86.7 percent), and NS5B S282T in none.
Sustained viral response was achieved by 13 patients (86.7 percent) overall, and all 15 patients completed therapy. The two patients who failed SOF, LDV and RBV combination therapy were elderly women, had the IL28B non-TT genotype, and had NS5A RAVs in L31I/Y93H or NS5A A92 K at baseline.
There were no reports of severe adverse events.
The findings suggest that adding RBV to interferon-free direct-acting antiviral (DAA) therapy may improve treatment outcomes in difficult-to-treat patients with genotype 1 HCV infection.
The development of DAAs has enabled dramatic improvements in anti-HCV treatment efficacy, with about 85 to 95 percent of patients achieving SVR. Patients who fail to respond to DAA-containing regimens, on the other hand, have a high rate of emerging RAVs, and an effective retreatment regimen for these patients has yet to be established. [Lancet Infect Dis 2015;15:645–53; Hepatology 2014;59:2083–91; Hepatol Res 2016;doi:10.1111/hepr.12851; J Hepatol 2017;66:153–94]