Highlights
- •Patients achieve high SVR12 rates with sofosbuvir/velpatasvir/voxilaprevir after prior DAA failures.
- •Sofosbuvir/velpatasvir/voxilaprevir is a very safe and well tolerated combination.
- •GT3 cirrhotic patients with previous treatment with NS5A-inhibitors are poor responders.
- •GT3 is the only factor that impacts SVR12 rates in retreatment with sofosbuvir/velpatasvir/voxilaprevir.
Background & Aims
Around 5% of patients with chronic hepatitis C virus (HCV) infection treated with
direct-acting antiviral (DAA) agents do not achieve sustained virological response
(SVR). The currently approved retreatment regimen for prior DAA failure is a combination
of sofosbuvir, velpatasvir, and voxilaprevir (SOF/VEL/VOX), although there is little
data on its use in clinical practice. The aim of this study was to analyse the effectiveness
and safety of SOF/VEL/VOX in the real-world setting.
Methods
This was a prospective multicentre study assessing the efficacy of retreatment with
SOF/VEL/VOX in patients who had experienced a prior DAA treatment failure. The primary
endpoint was SVR 12 weeks after the completion of treatment (SVR12). Data on safety
and tolerability were also recorded.
Results
A total of 137 patients were included: 75% men, 35% with liver cirrhosis. Most were
infected with HCV genotype (GT) 1 or 3. The most common prior DAA combinations were
sofosbuvir plus an NS5A inhibitor or ombitasvir/paritaprevir/r+dasabuvir. A total
of 136 (99%) patients achieved undetectable HCV RNA at the end of treatment. Overall
SVR12 was 95% in the 135 patients reaching this point. SVR12 was lower in patients
with cirrhosis (89%, p = 0.05) and those with GT3 infection (80%, p <0.001). Patients with GT3 infection and cirrhosis had the lowest SVR12 rate (69%).
Of the patients who did not achieve SVR12, 1 was reinfected and 7 experienced treatment
failure (6 GT3, 1 GT1a). The presence of resistance-associated substitutions did not
impact SVR12. Adverse effects were mild and non-specific.
Conclusion
Real-world data show that SOF/VEL/VOX is an effective, safe rescue therapy for patients
with prior DAA treatment failure despite the presence of resistance-associated substitutions.
However, patients with liver cirrhosis infected by GT3 remain the most-difficult-to-treat
group.
Lay summary
Treatment with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) for 12 weeks is the
current recommendation for the 5% of patients infected with HCV who do not achieve
eradication of the virus under treatment with direct-acting antivirals. In a Spanish
cohort of 137 patients who failed a previous combination of direct-acting antivirals,
a cure rate of 95% was achieved with SOF/VEL/VOX. Genotypic characteristics of the
virus (genotype 3) and the presence of cirrhosis were factors that decreased the rate
of cure. Treatment with SOF/VEL/VOX is an effective and safe rescue therapy due to
its high efficacy and very good safety profile.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: June 13, 2019
Accepted:
June 1,
2019
Received in revised form:
May 25,
2019
Received:
January 16,
2019
Identification
Copyright
© 2019 Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.
