Most people
with hepatitis C virus (HCV) in the GECCO German hepatitis C cohort who were
treated with sofosbuvir/ledipasvir (Harvoni)
for 8 weeks in a real-world clinical setting achieved sustained virological
response, even those who are advised to stay on treatment for 12 weeks due to
factors such as liver cirrhosis, prior treatment experience or high HCV viral
load, according to a presentation at the 15th European AIDS
Conference last month in Barcelona, Spain.
The advent of direct-acting antiviral agents
(DAAs) in interferon-free regimens has brought about a revolution in hepatitis
C treatment, but there is still room to improve therapy, for example making
treatment shorter and offering better options for the most difficult-to-treat
patients. While 12-week post-treatment sustained virological
response (SVR12) rates now exceed 90% in clinical trials, real-world experience
does not always match up.
Patrick Ingiliz of the Centre for Infectiology in Berlin reported findings from an analysis of
real-life hepatitis C treatment using DAAs in the GECCO cohort, an ongoing
multi-centre cohort that includes patients at eight sites in Germany.
Glossary
- FibroScan
A non-invasive test, used instead of a biopsy, to measure the stiffness
or elasticity of the liver using an ultrasound probe.
Short-course DAA therapy might be an attractive option to reduce
treatment costs or reduce the duration of drug toxicity, the researchers noted
as background.
Prescribing information for Gilead Sciences’ sofosbuvir/ledipasvir
coformulation, marketed as Harvoni,
states that previously untreated people with HCV genotype 1 or 4, with or
without cirrhosis, and treatment-experienced people without cirrhosis, should
take sofosbuvir/ledipasvir for 12 weeks. Treatment-experienced people with
cirrhosis should extend treatment to 24 weeks, while genotype 1 treatment-naive
people without cirrhosis and low HCV viral load can consider shortening it to 8
weeks. People with HIV and HCV co-infection should receive the same regimens as
those with HCV alone.
Among treatment-naive
participants without cirrhosis in the ION-3 trial, SVR12 rates were
94% using an 8-week regimen and 96% using a 12-week regimen, with people in the
8-week arm being more likely to relapse after finishing treatment.
GECCO was started in February 2014 and more
than 1000 patients have started interferon-free DAA treatment to date. The current
analysis focused on 148 participants (13% of the total) treated with sofosbuvir/ledipasvir
for 8 weeks.
In this subgroup half were men, the median age was 52 years and a third
had injection drug use as a transmission risk. Almost all (97%) had HCV
genotype 1, with 2% having genotype 4. Median pre-treatment HCV viral load was
810,000 IU/ml, 18% had received prior hepatitis C treatment and 3% had
cirrhosis according to FibroScan or APRI biomarker scores.
The group included 28 people with HIV and HCV co-infection (19% of the
total) with a median CD4 count of 531 cells/mm3. Compared to the group
as a whole, participants with co-infection were more likely to be men (82%),
more likely to have acquired HCV via sex (50%) and more likely to have HCV
genotype 4 (11%). They had a lower median HCV viral load (490,000 IU/ml) and two
people (7%) had cirrhosis.
Ingiliz reported SVR4 rates at 4 weeks post-treatment for 105 people who
had reached this time point. The overall SVR4 rate was 99.0%, with a single
person having detectable HCV RNA. SVR4 rates were 100% for subgroups with
various factors previously associated with poorer response, including HIV and HCV
co-infection, prior treatment, cirrhosis, high HCV viral load and genotype 4 –
though some of these numbers were small. SVR4 is not yet considered a cure, as
a small proportion of people still relapse after this point.
Looking at the 70 people who reached 12 weeks post-treatment, the
overall SVR12 rate was 98.5%, again with one person having detectable HCV viral
load. Response rates remained at 100% for the subgroups, but the numbers were
even smaller.
Sofosbuvir/ledipasvir was generally safe and well-tolerated with no
treatment discontinuations. The most common side-effects were headache (10%),
fatigue (7%), nausea (3%) and joint pain (2%).
Based on these findings the researchers concluded, "Sofosbuvir plus
ledipasvir for 8 weeks achieved excellent response rates in a German real-life
setting," adding that "HIV co-infected patients responded as well as
HCV monoinfected patients."
Ingiliz noted that SVR rates were high even for participants who were
treated "outside the recommendations" for this short regimen,
including people with treatment experience, cirrhosis, high viral load and
genotype 4.
Asked whether these results show that sofosbuvir/ledipasvir can be used
outside of current recommendations, Ingiliz replied that he would not advise
doing so. "Maybe from a cost perspective, but not from a virological
one," he said. "People with high viral load may still need longer
treatment."