People with chronic
hepatitis C who are using methadone or buprenorphine to manage opiate addiction
can be safely and effectively treated with AbbVie's 3D all-oral direct-acting
antiviral regimen plus ribavirin, resulting in a 97% cure rate, according to a
report this week at the 20th International AIDS Conference in Melbourne.
Hepatitis C virus (HCV) is readily transmitted
through shared needles and other drug injection equipment, and people who
inject drugs have high rates of HCV infection worldwide. Traditionally,
however, only a small proportion of this population has received hepatitis C
treatment due to concerns -- both real and unfounded -- about tolerability,
adherence and suboptimal efficacy.
New direct-acting antiviral agents that target different
steps of the HCV lifecycle have brought about a revolution in hepatitis C treatment. Recent studies have shown that combinations of two or more DAAs
without interferon can produce cure rates in the 90% range for most patient
AbbVie's 3D regimen consists of the HCV protease
inhibitor ABT-450, a 100mg boosting dose of ritonavir and the NS5A inhibitor
ombitasvir (formerly ABT-267) in a once-daily fixed-dose coformulation, taken
with the twice-daily HCV polymerase inhibitor dasabuvir (ABT-333) and
ribavirin. As previously reported, the combination cured 96% of both previously untreated and treatment-experienced patients with genotype 1 HCV infection.
Daniel Cohen of AbbVie presented findings from a phase
2 study evaluating the safety and efficacy of the 3D
combination for people with genotype 1 chronic hepatitis C who were on stable
opioid replacement therapy using either methadone or buprenorphine, with or
without naloxone. Previous
drug-drug interaction studies found that the AbbVie drugs had no notable effect
on methadone or buprenorphine pharmacokinetics.
The analysis included 38 participants at eight sites
in North America. Two-thirds were men, almost all were white and the mean age
was 48 years. 68% had harder-to-treat HCV subtype 1a, the rest 1b. One-third
had the favourable IL28B CC gene variant. Most (95%) had never before been
treated for hepatitis C.
Most participants had absent-to-mild (stage F0-F1)
liver fibrosis, but 16% had moderate (stage F2) and 5% had advanced (stage F3)
fibrosis; the study did not include people with cirrhosis (stage F4). People
with HIV or hepatitis B coinfection were also excluded.
In this open-label study all participants -- split
evenly between methadone and buprenorphine recipients -- were treated with the
3D combination plus weight-based ribavirin for 12 weeks. They were followed for
24 weeks after completion of therapy to determine sustained virological
response, or continued undetectable viral load (SVR24). Undetectable HCV RNA at
12 weeks post-treatment (SVR12) is considered a cure.
All but one patient had undetectable HCV RNA at the
end of treatment and maintained this response through 24 week post-treatment,
resulting in SVR12 and SVR24 rates of 97%. The remaining participant dropped
out of the study at week 2. There were no cases of viral breakthrough or
The 3D regimen plus ribavirin was generally safe and
well-tolerated. Only two participants (5.3%) experienced severe adverse events
(a stroke and cancer), including the aforementioned patient who discontinued
early for this reason. The most common side-effect were nausea (50%), fatigue
(47%), headache (32%), insomnia (18%) and rash (16%). Two people had low
haemoglobin levels -- a know side-effect of ribavirin -- but none developed
No participants required adjustment of methadone or
buprenorphine doses during hepatitis C treatment.
"The 3D + ribavirin regimen achieved an SVR24
rate of 97.4% among these 38 genotype 1-infected patients receiving opioid
replacement therapy," the researchers concluded. These findings were
"comparable to results previously reported in both treatment-naive and
treatment-experienced genotype 1-infected patients."
"A 12-week, highly efficacious, well-tolerated
all-oral regimen may be an attractive treatment option for genotype 1-infected
patients receiving opioid replacement therapy," they suggested, and
"patients on stable opioid replacement therapy may be well suited to
all-oral treatment for HCV."
Cohen said that prior
studies have shown that the 3D regimen is highly effective for people with
interactions with methadone and buprenorphine "may be unpredictable in
people with advanced liver disease."
Cohen also noted that the participants demonstrated
"very good adherence," according to pill counts, indicating that
provider concerns about people who use drugs being unable to stay on therapy
are not a reason to withhold treatment with effective new interferon-free