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Risk of reinfection is a concern after successful hepatitis C treatment
Liz Highleyman, 2016-09-28 07:30:00
People on opiate agonist substitution therapy can be
successfully treated with grazoprevir/elbasvir (Zepatier) – achieving cure rates similar to those of the population
as a whole – but some people are reinfected with hepatitis
C virus after being cured, suggesting that a greater emphasis on post-treatment
prevention may be needed, according to presentations at the 5th International Symposium on Hepatitis Care in
Substance Users (INHSU 2016) this month in Oslo.
Hepatitis C virus (HCV) is easily transmitted through
shared drug injection equipment and current and former injection drug users
have high rates of infection. However, some providers and insurers still
consider people who inject drugs to be poor candidates for hepatitis C
treatment and people who use drugs have
typically been excluded from most clinical trials of new hepatitis C therapies.
An exception was the C-EDGE CO-STAR study, a phase 3
trial evaluating Merck's HCV NS3/4A protease
inhibitor grazoprevir and HCV NS5A inhibitor elbasvir, which was specifically
designed for injection drug users receiving opioid substitution therapy (OST).
At INHSU, Olav Dalgard of Akershus
University Hospital in Oslo reported findings from an analysis of reinfections in CO-STAR. Later the same day, Håvard Midgard, also at Akershus University, discussed the clinical and
public health implications of HCV reinfection following sustained virological
It is not clear how often
HCV reinfection occurs. Dr Midgard reviewed 11 published studies of reinfection
among people who inject drugs, including several from the interferon era, which
found reinfection rates of 5 per 100 person years (PY) or less (pooled estimate
2.1). Looking at a smaller subset of people who inject drugs who were reinfected
after treatment, rates were around 10 per 100 PY or less (pooled estimate 5.6).
Some have suggested that
HCV reinfection might be more likely in the interferon-free era because
direct-acting antiviral treatment is faster, better tolerated and much more
effective than interferon-based therapy, leading people to be less careful
about avoiding getting infected again.
But there is little
evidence that this is the case. Tyler Raycraft of the University of British
Columbia presented a comparison of HCV recurrence among active drug users
treated with all-oral versus interferon-based regimens. Overall, four out of 77
patients were reinfected, all of them interferon recipients, leading the researchers
to conclude that “all-oral regimens for HCV treatment of active PWID [people
who inject drugs] is not associated with higher recurrent viremia rates compared
to interferon regimens.”
It can be difficult to
tell whether people who have detectable HCV viral load after 12 or 24 weeks of
post-treatment follow-up have relapsed or were reinfected, Dr Midgard
explained. Determination is straightforward if someone is reinfected with a
different HCV genotype, but not if they get a similar strain again. However,
late relapse after SVR12 is rare among people treated with direct-acting
antivirals. Another possibility is that treatment could eliminate the major
strain of HCV but leave behind a minor variant to take over, but this is also
thought to be rare.
“The more you look, the more you find,” Dr Midgard
said, noting that most studies have not retested for HCV often and would have
missed reinfections that cleared spontaneously.