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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 response (SVR).

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.