Does ribavirin improve efficacy of SOF/VEL/VOX in HCV retreatment?

The combination of sofosbuvir, velpatasvir, and voxilaprevir (SOF/VEL/VOX) with or without ribavirin demonstrates efficacy for the retreatment of patients with hepatitis C virus (HCV) infection in whom prior direct-acting antiviral (DAA) treatment has failed, a study in Egypt has shown.

However, SOL/VEL/VOX plus ribavirin is associated with more adverse events (AEs), which makes SOF/VEL/VOX monotherapy the preferred retreatment strategy.

“Ribavirin did not increase the cure rate compared to SOF/VEL/VOX monotherapy but led to more AEs,” the researchers said.

In this study, 315 HCV patients with DAA treatment failure from five Egyptian sites were randomized into group A (n=158; SOF/VEL/VOX monotherapy for 12 weeks) or group B (n=157; SOF/VEL/VOX plus weight-based ribavirin for 12 weeks). Therapeutic efficacy was defined as sustained virologic response 12 weeks after treatment end (SVR12).

Finally, the researchers assessed both safety and tolerability by monitoring treatment-related AEs and laboratory abnormalities.

The corresponding mean ages of patients in groups A and B were 51.8 and 47.3 years and consisted of 53.9 percent and 57.1 percent of males (p=0.58), respectively. Seventeen patients in each group were lost to follow-up. [J Hepatol 2023;79:314-320]

The intention-to-treat analysis revealed SVR12 rates of 87.3 percent in group A and 87.9 percent in group B, while the per-protocol analysis showed rates of 97.8 percent and 98.5 percent, respectively (p-value not significant for both intention-to-treat and per-protocol analyses).

Patients in both regimens tolerated the treatment well, with no deaths reported and only one serious AE (anaemia) in group B, leading to ribavirin discontinuation. In addition, 55 patients in group A and 77 in group B experienced an AE (p=0.002).

Egyptian experience

Across the world, Egypt has the highest HCV prevalence, with almost one in 10 citizens being HCV antibody positive in 2015. [World J Gastroenterol 2018;24:4330-4340]

The American Association for the Study of Liver Diseases and the European Association for the Study of the Liver recommend retreatment of patients with DAA failure using SOF/VEL/VOX for 12 weeks or glecaprevir/pibrentasvir plus SOF and ribavirin for 16 weeks. [J Hepatol 2020;73:1170-1218; www.hcvguidelines.org/treatment-experienced]

However, the guidelines set by the Egyptian National Consensus Committee on Viral Hepatitis only recommend SOF/VEL/VOX due to the limited availability of glecaprevir/pibrentasvir.

“Considering that Egypt has now treated more than four million patients with DAA therapy, even with a 98.8-percent SVR rate, this translates to at least 48,000 patients who fail to clear the virus,” the researchers said. “The Egyptian guidelines recommend retreatment with SOF/VEL/VOX in this group, but for those who fail this retreatment, there is no further retreatment option.”

For that reason, any additive therapy that could improve the SVR rate even by a tiny percentage, which would then translate into thousands of patients more who can be cured, is important, according to the researchers.

“Accordingly, this question of the additive efficacy of ribavirin when given alongside SOF/VEL/VOX is not only of great practical interest to Egypt but likely could only be studied in Egypt, given the huge numbers of patients who have been treated for HCV,” they noted.