Most people who
inject drugs completed treatment with sofosbuvir/velpatasvir (Epclusa)
and achieved sustained
virological response (SVR) in a real-world setting, even if they had
interruptions in therapy, according to a presentation at the AASLD Liver
Meeting this week in San Francisco.
Hepatitis C virus (HCV) is readily transmitted through
shared syringes and people who inject drugs have high rates of HCV
incidence and prevalence worldwide. Experts and advocates emphasise that
widespread treatment of current and former injection drug users will be
necessary to meet the World
Health Organization goal of eliminating hepatitis C as a
public health threat by 2030.
However, many people who inject drugs have not been tested for HCV and do
not know their status. In addition, this population has traditionally been denied access to treatment
because of concerns about poor adherence or reinfection after being cured. Yet
clinical trials have shown that people who inject drugs
can achieve high cure rates using direct-acting antivirals (DAAs).
Dr Elana Rosenthal of the University of Maryland
School of Medicine presented results from the ANCHOR study, which evaluated
hepatitis C treatment offered at an urban harm reduction centre in Washington,
DC. Earlier this year Rosenthal reported that combining
HCV treatment with opioid substitution therapy using
buprenorphine improved adherence and reduced harms associated with drug
injection.
At the AASLD meeting, Rosenthal
presented findings from an analysis of how imperfect medication adherence and
gaps in therapy affect treatment success.
The
study enrolled 100 participants with chronic HCV infection and opioid use disorder who
had injected drugs within the past 3 months. Three-quarters were men, more than
90% were black and the median age was 57 years. About a third had compensated
cirrhosis, but those
with decompensated liver disease were excluded.
About 60% said they
injected opioids at least once daily, a third reported receptive sharing of
injection equipment (meaning someone else used
it first) during the past 3 months and 40% reported hazardous alcohol use. In this
analysis, only a third were on opioid substitution therapy for addiction.
Rosenthal described
the participants as an "incredibly marginalized population." About
half were homeless or unstably housed, 92% had a history of incarceration and
more than 90% had either no income or only government benefits.
All study
participants were prescribed 12 weeks of treatment with Epclusa, a one-pill, once-daily pan-genotypic
regimen that is effective against all HCV genotypes. Medication was dispensed in bottles containing 28 pills
at baseline and at weeks 4 and 8.
Rosenthal's
team measured HCV viral load at week 4 as an early marker of adherence and
asked about interruptions in treatment, the number of pill bottles finished
and, for those who finished all three bottles, when the last pill was taken.
Adherence
was good overall. Attendance at the 4-week follow-up visit was 88%, and at that
point 89% had undetectable HCV viral load (< 200 IU/ml). Attendance dipped to
70% at the 12-week visit, but returned to 88% at the final 24-week visit.
The
overall cure rate was 78% in an intention-to-treat analysis of the 93
participants who completed 12 weeks of post-treatment follow-up. One in 10
experienced virological treatment failure, 9% were lost to follow-up and one
person died. In a per-protocol analysis of the 82 individuals who remained in
the study, the SVR rate was 88%.
Viral
load at week 4 was a good predictor of which people would go on to be cured.
Among those with undetectable HCV RNA at that point 4, 86% achieved SVR,
compared with just 25% of those with detectable viral load.
Most
participants finished all three bottles of Epclusa,
and their SVR rate was 85%. Another seven people took at least two full
bottles, with an SVR rate of 71%. However, none of the six participants who
finished less than two bottles were cured.
Twenty
people finished treatment on time in 12 weeks, achieving an SVR rate of 95%.
Another 43 people took longer to complete the 12 weeks worth of medication
due to gaps in therapy, but they still had a high cure rate of 88%. Thirteen
people did not complete treatment, and their SVR rate fell to 38%.
"As
long as patients completed the prescribed amount, imperfect adherence was not
associated with decreased cure rates," Rosenthal said.
Thirteen
participants reported treatment gaps at some point during the 12-week course of
therapy. Nine of these interruptions lasted 10 days or longer, with the longest
being 70 and 196 days. Reasons for treatment interruption included medications being
lost or stolen, hospitalisation, incarceration and entering inpatient drug
treatment.
People
with no treatment gaps had an SVR rate of 86%, compared with 67% for those with
any interruptions. Everyone who had gaps lasting 3 to 10 days, as well as the
two people with the longest gaps, were all cured. However, three people with intermediate
gaps of 14, 15 and 30 days did not achieve SVR.
The
likelihood of being cured was not affected by daily injections, unstable
housing, hazardous drinking or lack of opioid substitution therapy, Rosenthal
said.
"PWID [people who inject drugs] have high rates of completion of DAA
therapy and achieve high rates of SVR," the researchers concluded. "Imperfect adherence does not seem to impact
SVR outcomes, even in patients with interruptions in treatment. Completion of
at least 8 weeks of [Epclusa] is
important for achieving SVR."
"Our data
demonstrate that people who inject drugs can achieve SVR at comparable rates to
non-drug using populations, even if adherence is imperfect," Rosenthal
said. "Therefore, there is no justification for excluding people who
inject drugs from being treated. In fact, people who inject drugs should
represent a unique high-priority population, because injection drug use remains
the primary reason for on-going HCV transmission in the U.S. Therefore,
treatment of people who inject drugs will help prevent new cases of HCV."