Retreatment of hepatitis C — sofosbuvir/velpatasvir/ voxilaprevir (SOF/VEL/VOX) 1

In the RESOLVE study, 77 patients with hepatitis C who had
previously failed direct acting antiviral therapy (DAA) were
treated with SOF/VEL/VOX for 12 weeks. All patients had genotype
1 with 58/77 1a and the remainder 1b. 40 % had compensated
cirrhosis. 17 patients were coinfected with HIV and were
on antiretroviral therapy. Most coinfected patients had dolutegravir
containing antiretroviral therapy. According to an intention
to treat analysis 70/77 patients (90.9 %) achieved sustained
viral response 12 weeks after the end of treatment (SVR12).
In a per protocol analysis where only patients who completed
12 weeks of therapy and all study visits were included, 70/71
achieved SVR12. The one patient who failed was HIV coinfected,
had non-detectable virus at week 4 and through the end of
therapy, but relapsed by post treatment at week 4. The patient
had good adherence and denied any re-exposure. He was infected
with the original genotype. Of the remaining 6 patients,
3 discontinued early (one due to a subdural hematoma, one
hypertensive stroke and one because of colitis), 1 died, and 2
were lost to follow up. The patients who died developed hepatic
decompensation at week 9 due to thrombosis of the hepatic
vein and was diagnosed with hepatocellular carcinoma. An ultrasound
6 months prior to the study had been negative. 14/17
patients with HIV coinfection achieved SVR12. Post treatment
resistance tests were available in four patients who did not
achieve SVR12. All four patients had resistance mutations. As
these patients had been treated with DAAs previously and no
baseline resistance tests were available it is unclear to what extent
these mutations were preexisting. In summary the authors
conclude that retreatment with SOF/VEL/VOX is safe and effective
in patients who had previously failed DAA treatment
and that treatment response is not affected by HIV-coinfection.

Ref; Wilson et al. J Hepatology 2019;71:498-504

Comment: SOF/VEL/VOX is an effective and safe retreatment
for patients who have failed previous DAA-treatment. A limitation
of the study is that all patients had genotype 1.