An eight-week course of grazoprevir/pibrentasvir (Zepatier)
achieved a high cure rate in people recently infected with hepatitis C, but
another study found that a six-week course of sofosbuvir/velpatasvir (Epclusa)
resulted in an inferior cure rate compared to standard treatment, recent
Both studies tested shorter durations of treatment predominantly
in people coinfected with HIV and hepatitis, as the incidence of new hepatitis
C infections and reinfections in HIV-positive gay and bisexual men makes treatment
of acute infection a priority for hepatitis C control in this population.
Short-course treatment for acute hepatitis C infection
remains experimental. The
AASLD Hepatitis C treatment guidelines say that as of November 2019, there
isn’t enough evidence to recommend any short-course regimen and that acute
infection should be treated in the same way as chronic infection. The only
8-week pangenotypic regimen approved for chronic hepatitis C treatment is
Short-course treatment for hepatitis C may improve adherence
and should prove more cost-effective than standard-duration treatment in acute
infection. It’s unclear if shortening the duration of treatment also reduces
the risk of onward transmission.
Two recent pilot studies reported on short-course treatment.
Short-course treatment with grazoprevir/elbasvir
The French SAHIV study evaluated an eight-week course of
treatment with grazoprevir/elbasvir in recently infected gay and bisexual men.
Grazoprevir/elbasvir is approved for chronic genotype 1 or 4 infection as a
12-week course of once-daily treatment. A
study in the Netherlands and Belgium has shown that an 8-week regimen achieved
a 94% cure rate in coinfected men.
The study recruited 30 people who had tested positive for HCV
RNA or antibody less than six months after a negative HCV test (or less than
six months after a potential exposure and less than 12 months after a previous
negative test, including ten people who had been reinfected.
All were male. Twenty-three reported probable exposure through
sex, six through nasal drug use and five through injecting drugs. Two had
unknown exposure routes.
Twenty-eight out of 30 were coinfected with HIV, all were
taking antiretroviral therapy and 26 of 28 had an undetectable viral load at
Twenty-eight out of 30 who completed treatment achieved a
sustained virologic response (91%). One participant committed suicide and one
participant experienced viral rebound after completing treatment. This
participant had undetectable levels of HCV drugs and low levels of HIV drugs at
week 4 of the study, undetectable HCV RNA levels after completing treatment and
experienced viral rebound 12 weeks after completion of treatment. Resistance to
the study medication was detected.
Adherence to grazoprevir/elbasvir was similar to
antiretroviral adherence during the study; 7% of participants reported missing
a dose of hepatitis C treatment in the past four days at the week 8 study visit.
No serious drug-related adverse effects were reported by
study participants and the most common side-effects were diarrhoea, insomnia and
Three participants subsequently became reinfected within a
year of completing treatment and were successfully re-treated.
Short-course treatment with sofosbuvir/velpatasvir
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-weeka 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. 82% 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 different in the proportions with
undetectable viremia 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.