Adding Ribavirin to Combination Therapy for HCV Does Not Increase Cure Rate

Combination therapy with sofosbuvir, velpatasvir, and voxilaprevir should remain the preferred retreatment strategy for HCV.

The addition of ribavirin to the combination of sofosbuvir, velpatasvir, and voxilaprevir for treatment of direct-acting antiviral (DAA) failure did not improve sustained virological response (SVR) rates in patients with hepatitis C virus (HCV) and was associated with more adverse events, according to study results in the Journal of Hepatology.

Researchers conducted a randomized controlled trial ( Identifier: NCT04695769) to compare sofosbuvir, velpatasvir, and voxilaprevir with or without ribavirin in patients with chronic HCV who failed to respond to first-line DAA therapy.

Participants were adult patients (aged ≥18 years) with chronic hepatitis C that was detectable by HCV RNA polymerase chain reaction (PCR) after completing a previous DAA regimen. They were also eligible for antiviral treatment.

The patients were randomly assigned 1:1 to receive a fixed-dose combination of sofosbuvir, velpatasvir, and voxilaprevir (group A) or a fixed-dose combination of sofosbuvir, velpatasvir, and voxilaprevir with ribavirin (1,000 or 1,200 mg daily based on the patient’s body weight: <75 kg or >75 kg) (group B). The treatment duration was 12 weeks in the 2 groups.

Addition of ribavirin to SOF/VEL/VOX increased adverse events but not SVR rates in retreatment of patients who failed DAA therapy.

The primary endpoint was treatment efficacy, which was defined as the achievement of SVR-12 confirmed by undetectable HCV RNA by PCR 12 weeks after the end of treatment.

Group A included 158 patients in the intention-to-treat (ITT) protocol and 141 in the per protocol (PP) analysis, and group B included 157 participants in the ITT protocol and 140 in the PP analysis. The overall mean age of participants was 49.6 years, and 55.5% were men. The sofosbuvir, velpatasvir, and voxilaprevir group had a higher proportion of patients with a fibrosis-4 (FIB-4) less than 1.45 vs the ribavirin group (35.5% vs 17.1%) and a greater proportion of patients with a FIB-4 greater than 3.25 (53.9% vs 20%).

The overall SVR rates in the 2 treatment groups were not different. The SVR12 in group A was 87.3% (138/158) in the ITT and 97.9% (138/141) in the PP analyses. In group B, the corresponding rates were 87.9% (138/157; P = .88) and 98.6% 138/157; P = .66). The ribavirin-containing group had an increased rate of adverse events (77 vs 55, P = .002), with fatigue and headache the most common side effects. No deaths occurred, and 1 serious adverse event of anemia that required hospitalization occurred in the ribavirin group.

In stratification with cirrhosis, no differences were observed in efficacy or adverse events between the 2 groups. For a subgroup of patients with FIB-4 greater than 3.25, no statistical difference was found in the rate of SVR12 between patients who received ribavirin (28/28) and those who did not (21/23) (P = .198). No difference occurred in the rate of adverse effects between the ribavirin group (n=13) and those without ribavirin (n=14); (P = .288)

Study limitations include the absence of genotyping for all patients, as well as missing SVR data in about 11% of both cohorts. In addition, FIB-4 was used to estimate the prevalence of cirrhosis.

“Addition of ribavirin to SOF/VEL/VOX [sofosbuvir, velpatasvir, and voxilaprevir] increased adverse events but not SVR rates in retreatment of patients who failed DAA therapy,” the researchers wrote. “Therefore, the preferred retreatment strategy should be SOF/VEL/VOX monotherapy.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


El-Kassas M, Emadeldeen M, Hassany M, et al. A randomized controlled trial of SOF/VEL/VOX with or without ribavirin for retreatment of chronic hepatitis C. J Hepatol. Published online April 21, 2023. doi:10.1016/j.jhep.2023.04.011