HCV Genotype, First-Line Therapy Do Not Impact Salvage Therapy Response

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Sofosbuvir/velpatasvir/voxilaprevir rescue therapy was safe and effective, and SVR did not significantly differ based on genotype, cirrhosis, or first-line therapy.

Combination sofosbuvir, velpatasvir, and voxilaprevir (SOF/VEL/VOX) is a safe and effective rescue therapy for patients with hepatitis C virus (HCV) who previously failed sofosbuvir/velpatasvir (SOF/VEL) and glecaprevir/pibrentasvir (GLE/PIB), according to findings from a recent study.1

Among a cohort of more than 100 patients who completed SOF/VEL/VOX therapy and 12 weeks of follow-up, 88.6% achieved sustained virological response (SVR). Although there was a trend toward lower SVR in patients with genotype 3 HCV infection, cirrhosis, and first-line therapy with SOF/VEL, these associations did not reach statistical significance.1

According to the World Health Organization (WHO), globally, an estimated 50 million people have chronic hepatitis C virus infection, with about 1 million new infections occurring per year. Although direct-acting antivirals can cure more than 95% of HCV cases, treatment failure remains an issue hindering the WHO’s global hepatitis strategy to eliminate viral hepatitis as a public health threat, which calls for reductions in new hepatitis infections by 90% and deaths by 65% between 2016 and 2030.2,3

Maria Buti, MD, PhD, professor of medicine at the Hospital General Universitari Valle d’Hebron in Spain, and colleagues noted the current recommendation for using SOF/VEL/VOX as salvage therapy after DAA failure is based on studies that “included a limited number of patients, especially those with cirrhosis and HCV GT3 infection, and almost all the participants had failed treatments that are no longer recommended as first-line therapy. In addition, patients with decompensated cirrhosis or human immunodeficiency virus (HIV) coinfection were excluded.”

To assess the efficacy and safety of SOF/VEL/VOX for HCV retreatment among patients who failed SOF/VEL or GLE/PIB, investigators conducted an observational, retrospective, multicenter study among patients treated at 26 Spanish hospitals from December 2017 to December 2022. Investigators pointed out some patients received ribavirin in addition to SOF/VEL/VOX at their clinician's discretion.1

For inclusion, patients were required to be ≥ 18 years of age, have chronic HCV infection, and have a history of unsuccessful response to SOF/VEL or GLE/PIB. Patients with decompensated cirrhosis or hepatocellular carcinoma (HCC) were included, as were those with hepatitis B virus (HBV) or HIV coinfection. However, patients who experienced HCV reinfection after achieving SVR with first-line therapy were excluded.1

Adverse events were recorded during the course of SOF/VEL/VOX treatment and up to 12 weeks after the end of treatment. The primary endpoint was the SVR rate, defined as an HCV RNA level below the lower limit of quantification at least 12 weeks after the end of treatment.1

In total, 142 patients were included in the present study, 100 (70.4%) of whom had failed SOF/VEL and the remaining 42 (29.6%) GLE/PIB. Patients were mainly male (84.5%), White (93.9%), with HCV genotype 3 (49.6%) and liver cirrhosis (47.2%).1

Among the cohort, 132 patients successfully completed SOF/VEL/VOX therapy, allowing for SVR evaluation. By intention to treat analysis, the SVR rate was 82.4% (117/142). However, investigators pointed out in per protocol analysis, the SVR rate was 88.6% (117/132), noting 11.4% (n = 15) did not respond to SOF/VEL/VOX despite completing treatment with optimal adherence.1

Investigators observed that patients who did not achieve SVR after SOF/VEL/VOX were mainly male (80%), White (92.3%), 11 had previously received SOF/VEL, 9 had genotype 3 infection, and 8 had cirrhosis. However, upon analysis, there were no significant differences in SVR rates according to initial DAA treatment (SOF/VEL 87.9% vs GLE/PIB 90.2%; P = .8), cirrhosis (no cirrhosis 90% vs cirrhosis 87.1%; P = .6) or genotype 3 infection (non-genotype 3 91.9% vs genotype 3 85.5%; P = .3).1

However, investigators outlined several potential limitations to these findings, including the small sample size, the limited number of failures to SOF/VEL/VOX, and the retrospective study design.1

“Our results provide evidence that SOF/VEL/VOX is an effective and safe rescue therapy for patients with HCV infection and nonresponse to SOF/VEL or GLE/PIB,” investigators concluded.1


  1. Ruiz-Cobo JC, Llaneras J, Forns X, et al. Real-life effectiveness of sofosbuvir/velpatasvir/voxilaprevir in hepatitis C patients previously treated with sofosbuvir/velpatasvir or glecaprevir/pibrentasvir. Alimentary Pharmacology and Therapeutics.
  2. World Health Organization. Hepatitis C. Newsroom. April 9, 2024. Accessed May 8, 2024.
  3. World Health Organization. Elimination of hepatitis by 2030. Hepatitis. Accessed May 8, 2024.