A brief report in the same journal described a
similar pooled analysis of the ASTRAL trials, also led by Dr Grebely.
Unlike ledipasvir, which is active against
HCV genotypes 1, 4, 5 and 6, velpatasvir is also effective against genotypes 2
and 3. Genotype 3, which is common among people who inject drugs, is considered
the hardest type to treat with direct-acting antivirals.
As previously reported, ASTRAL-1 enrolled 740 people with all HCV genotypes except 3, ASTRAL-2 enrolled
266 people with genotype 2 and ASTRAL-3 enrolled 552 people with genotype 3.
(ASTRAL-4, which looked at people with decompensated cirrhosis, and ASTRAL-5,
which enrolled people with HIV/HCV co-infection, were not included in this pooled
analysis.)
Participants in
ASTRAL-1 were randomly assigned to receive the once-daily fixed-dose
sofosbuvir/velpatasvir combination or placebo for 12 weeks, ASTRAL-2
participants received sofosbuvir/velpatasvir or sofosbuvir plus ribavirin for 12 weeks, and
ASTRAL-3 participants received sofosbuvir/velpatasvir
for 12 weeks or sofosbuvir plus ribavirin for 24 weeks.
Among the 1035 participants treated with
sofosbuvir/velpatasvir in the three trials, 51 (5%) were on OST using methadone
or buprenorphine. Three-quarters were men, the mean age was 49 years, 22% were
treatment-experienced and 25% had cirrhosis. Nearly half (47%) had HCV genotype 3,
followed by 1a (24%), 2 (16%) and 4 (12%); just one person had subtype 1b and
none had genotypes 5 or 6.
The overall SVR12 rate
for OST users was 96% – similar to the 95 to 99% cure rates seen across all
study participants. The cure rate was also 96% for hard-to-treat genotype 3. Of
the two participants on OST who did not achieve SVR12, one
discontinued treatment after a single dose due to adverse events and one was
lost to follow-up after 5 days of treatment.
Here too, the
investigators found that OST use did not affect the likelihood of treatment
completion (96% in the OST group vs > 99% in the non-OST group) or
maintaining at least 90% adherence (90% vs 96%, respectively). However, people on OST
with less than 90% adherence did not do as well as those with better adherence
(60% vs 100% SVR12).
Again,
treatment was safe and well tolerated for people on OST. There were more
serious adverse events in the OST group (6% vs 2%), but the difference was not
statistically significant.
No
cases of HCV reinfection were observed during 24 weeks of post-treatment
follow-up.
In
both of these analyses, the study authors concluded that OST during hepatitis C
therapy – and illicit drug use in the ION trials – "did not impact
treatment completion, adherence, SVR12 or safety."
These findings add to the evidence supporting
treatment for people who inject drugs – a population with the highest burden of
hepatitis C.
However, the researchers noted, these trials enrolled
selected cohorts of people on stable OST with recent illicit drug use excluded,
and therefore may not be representative of all people who inject drugs.