on opiate substitution therapy were successfully treated for hepatitis C with an
interferon-free regimen of grazoprevir/elbasvir (Zepatier), and only a small number became reinfected during three
years of follow-up, researchers reported yesterday at the 25th International Harm Reduction Conference (HR17) in Montréal.
Hepatitis C virus (HCV) is easily transmitted through shared drug
injection equipment. The advent of new direct-acting antivirals (DAAs) used in
interferon-free regimens has transformed hepatitis C treatment. But due to
their high cost, many providers, insurers and government payers have made
people who inject drugs ineligible for therapy, even though they make up a
large proportion of the population living with HCV.
"In many countries there are still restrictions based on drug
and alcohol use criteria, which is a human rights violation," said Jason
Grebely of the Kirby Institute at the University of New South Wales. "We
really need to be working to build the evidence base around how people can be
successfully treated with these new DAAs."
Grebely presented long-term follow-up results from the C-EDGE CO-STAR
study, a multinational Phase 3 trial evaluating
Merck's HCV NS3/4A protease inhibitor grazoprevir and HCV NS5A inhibitor
People who inject drugs have typically been excluded
from clinical trials of new hepatitis C therapies, and CO-STAR was
the first randomised controlled trial that specifically looked at treatment of
injection drug users receiving opioid substitution therapy (OST), Grebely said.
C-EDGE CO-STAR enrolled 301 previously
untreated people with hepatitis C with HCV genotypes 1, 4 or 6. About
three-quarters were men, most were white and the median age was about 45 years.
Around 80% had genotype 1a, one in five had liver cirrhosis and 7% had co-infection
Participants were required to be on stable OST using methadone or
buprenorphine for at least three months at study entry. Urine drugs screens
were done regularly, but people were not excluded from the trial if they
continued to use illicit drugs, as over half of them did.
In Part A of the study, participants were
randomly assigned to receive either grazoprevir/elbasvir or placebo once daily
for 12 weeks, at which point the study was unblinded and placebo recipients
were switched to grazoprevir/elbasvir on an open-label basis. Follow-up continued to 52 weeks.
As previously reported, 91%
of people treated with grazoprevir/elbasvir in the immediate and deferred groups
combined achieved SVR12, or undetectable HCV RNA at 12 weeks after completing
therapy, in an intent-to-treat analysis that counted people who were reinfected
as treatment failures. In a modified analysis that counted people who were
cured and then reinfected as successes, the SVR12 rate rose to 96%.
These cure rates were comparable to those seen in studies of people who
were not injection drug users. Treatment adherence was high (97%) and also
similar to what was observed in previous studies. Grazoprevir/elbasvir was generally safe and well tolerated, and people on OST
did not have more adverse events or side-effects than others treated with the
In Part B of the study, participants were followed for three years. They had visits every six months to assess HCV viral load,
and if positive, viral sequencing to compare the original virus to the
recurrent virus. Having different viruses indicates reinfection with a new virus
rather than late relapse or re-emergence of the original virus. Urine drug
screens were done and participants were asked about their drug use and related
Of the 301 participants in Part A, 199 enrolled in
Part B. Of these, 192 people completed six months, 161 people completed 12
months and 17 people completed 18 of follow-up.
Drug use stayed about the same during follow-up. At the time of
enrolment in Part A, 23% tested positive for cannabis, 22% for benzodiazepines,
21% for other opioids, 10% for cocaine and 6% for amphetamines. At enrolment in
Part B, the proportions testing positive were similar: 26%, 23%, 26%, 11% and
8%, respectively. Overall, 59% tested positive for any drug at six months,
compared to 56% at initial enrolment.
With regard to self-reported drug use, 21% said they
had injected drugs in the previous month and 25% had done so in the past six
months; 39% and 42%, respectively, reported using non-injected drugs.
Among participants who reported injecting any drugs
within the past month, 81% said they used sterile syringes all the time, 17%
did so most of the time and one person said they never used a clean needle. No
one reported receptive sharing, or using a needle after someone else had used
it. However, 42% said they had used other injection-related equipment or
supplies after someone else, including spoons, filters and water.
Looking at HCV reinfection, five participants were
reinfected through week 12 of follow-up, one more by week 24, and two more by
six months, for a total of eight reinfections, or 4.0 per 100 person-years. But
three of these people spontaneously cleared the new virus, so the rate of
persistent reinfection was lower, at 2.5 per 100 person-years.
Those who cleared HCV did so very quickly, Grebely said. Prior studies
have shown that 10 to 25% of people clear their initial HCV infection. The
reason for the higher reinfection clearance rate seen in this study might offer
clues for vaccine development, he suggested.
These results, Grebely concluded, support advocacy efforts to expand
hepatitis C treatment for people who inject drugs. He stressed the importance
of scaling up treatment quickly to reduce the prevalence of HCV in this
population, which would result in less reinfection.
At another conference session on
community-based hepatitis C treatment, speakers said they did not want to focus
on or study reinfection because it can be used as an excuse for not offering
treatment to people who continue to inject drugs.
The fact that some people get reinfected
reflects a lack of adequate harm reduction services and ready access to clean
injection supplies, they argued. Getting more people treated and cured would
also reduce the risk of reinfection.
"Reinfection is not about being
careless, it's about education and the availability of appropriate health care,"
said Mary Ellen Harrod of the New South Wales Users and AIDS Association.