A second study of treatment in acute or recent infection
found that six weeks of treatment with sofosbuvir/velpatasvir (Epclusa)
resulted in an inferior cure rate in people recently infected with hepatitis C
when compared to a 12-week treatment course.
A six-week course of sofosbuvir/ledipasvir (Harvoni) has
been shown to be an effective treatment for acute hepatitis C genotype 1 infection
in two single-arm studies but no randomised comparison of short-course versus
standard-course pangenotypic treatment has reported findings.
The REACT study was designed to test whether
sofosbuvir-velpatasvir was an effective treatment. The study enrolled people
who inject drugs and people with HIV who had been infected with hepatitis C less
than 12 months previously.
All study participants received six weeks of treatment with
sofosbuvir/velptasvir and were then randomised to stop treatment or continue for
a further six weeks.
Ninety-three people were randomised to the short-course arm
and 99 to the 12-week arm. The study population was almost entirely male (96%),
predominantly white (83%), just over two-thirds were HIV positive (70%), the predominant
route of exposure to hepatitis C was sex between men (72%) and 21% were injecting
drug users. Thirty-seven per cent were undergoing treatment due to reinfection.
Participants had been infected with hepatitis C for a median
of 25 weeks at study entry, predominantly with genotype 1 (65%), 3 (17%) or 4
The study Data and Safety Monitoring Board stopped the study
at the second scheduled review of the data in May 2019 due to an unacceptably
high rate of virological relapse in the short-course arm. Eighty-two per cent in the
short-course arm achieved a sustained virologic response compared to 91% in the
12-week arm (p = 0.063). Although there was no difference in the proportions with
undetectable viraemia at the end of treatment, nine people in the short-course
arm and two in the 12-week arm experienced viral rebound, despite excellent
adherence in those who experienced rebound. Those who experienced rebound tended
to have higher baseline viral load, but numbers were insufficient for an
analysis of predictors of rebound.
There was no substantive difference in deaths, loss to follow-up
or reinfection in the two study arms.
The reason for the higher rate of virological rebound in the
short-course arm is unclear. Only one person who experienced rebound had
sub-optimal adherence. It is possible that the combination of a nucleotide
analogue (sofosbuvir) and NS5A inhibitor (velpatasvir) may not induce
sufficiently rapid viral load reduction to permit a six-week treatment course.