Interferon-free treatment works well for people who inject drugs, but barriers to access remain

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Hepatitis C treatment for people who inject drugs, including those receiving opioid substitution therapy (OST), was a major theme of the 4th International Symposium on Health Care in Substance Users (INHSU 2015) last week in Sydney, Australia. Studies show that treatment using new interferon-free regimens can be highly effective for this population, but barriers including high drug costs and stigma against drug users have hindered widespread access to therapy.

Jordan Feld of the University of Toronto set the stage with an overview of the current state of hepatitis C treatment and what is known about treating people who inject drugs. He concluded that while current therapies are well-tolerated and highly effective, we do not yet have a regimen that’s optimal for everyone – dubbed ‘perfectovir’.

Although good options exist for HCV genotype 1, better regimens are needed for genotype 3 – and the best would be pan-genotypic regimens that do not require genotypic testing. Simpler regimens would allow HCV treatment to move out of specialist clinics. Everyone is eager for shorter treatment duration, but Feld cautioned that shortening therapy too much can lead to treatment failure and drug resistance – six weeks seems to be the “edge of the cliff,” he said.

Treatment for people who inject drugs

Early clinical trials of direct-acting antiviral agents generally excluded people who inject drugs – a holdover from the interferon era when many providers considered people who use drugs to be poor candidates for treatment.


opioid substitution therapy (OST)

Providing users of an illegal drug (such as heroin) with a replacement drug (such as methadone, buprenorphine or naltrexone) under medical supervision. This helps the person reduce the frequency of injections and their dependency on illegal drugs. It is part of a harm reduction approach.



sustained virological response (SVR)

The continued, long-term suppression of a virus as a result of treatment. In hepatitis C, refers to undetectable hepatitis C RNA after treatment has come to an end. Usually SVR refers to RNA remaining undetectable for 12 or 24 weeks after ending treatment and is considered to be a cure (SVR12 or SVR24).


Severe fibrosis, or scarring of organs. The structure of the organs is altered, and their function diminished. The term cirrhosis is often used in relation to the liver. 


A pill or liquid which looks and tastes exactly like a real drug, but contains no active substance.


In HIV, synonym for superinfection. In hepatitis C, used when someone who has been cured of the virus is infected with hepatitis C again.

Interferon/ribavirin therapy lasted up to a year, often caused depression and many experts felt it was contraindicated for people with mental health problems. Providers often expected that people who used drugs would not adhere to treatment and the need for weekly interferon injections raised fears about relapsing to illicit drug injection. And with all those drawbacks, it only cured about half of people treated.

But this has changed with the advent of interferon-free regimens, which use well-tolerated oral pills, usually taken for 12 weeks, and produce cure rates exceeding 90%. Some later trials of direct-acting antivirals in interferon-free regimens have permitted participants to be on OST.

Jason Grebely of the Kirby Institute at the University of New South Wales presented findings from a sub-group analysis of people on OST in Gilead Sciences’ phase 3 ION trials, evaluating the sofosbuvir/ledipasvir coformulation (Harvoni) taken for 8, 12 or 24 weeks with or without ribavirin.

Of the 1952 people with genotype 1 enrolled in the three ION studies, a total of 70 (4%) were receiving OST; people who were actively injecting drugs and not on OST were not eligible. Of these, 69% were men, 90% were white and the mean age was 47 years. Most (89%) were treatment-naive (had not taken treatment before) and 10% had liver cirrhosis.

The overall SVR12 rate (sustained virological response 12 weeks after the end of treatment – considered a cure) for people on OST was 94% – comparable to the 97% for other participants; ribavirin offered no added benefit. Similarly, people on OST were about equally likely to maintain at least 80% adherence (94% vs 96%, respectively). Treatment was safe and well-tolerated by people on OST. After treatment there have been no cases of HCV reinfection among people receiving OST.

More recently a small number of trials have specifically enrolled people who inject drugs. While there is a growing body of data on hepatitis C treatment for people on OST, research is still needed on treatment for current active drug injectors.


Gregory Dore, also of the Kirby Institute, presented early findings from the C-EDGE CO-STAR study, evaluating Merck’s grazoprevir and elbasvir. Participants were randomly assigned to receive either the grazoprevir/elbasvir fixed-dose combination or placebo for 12 weeks, after which the placebo recipients were also given active treatment.

This phase 3 study enrolled 301 previously untreated people with HCV genotypes 1, 4 or 6 (76% had hard-to-treat HCV 1a). About three-quarters were men, 80% were white, the median age was 48 years and 20% had cirrhosis. They were required to be on OST for at least three months and to have consistently kept at least 80% of their appointments.

About 60% of participants continued to use illicit drugs during the study (45% when excluding those who only used cannabis). All maintained at least 80% adherence to HCV therapy (>67 doses), 99% had at least 90% adherence (>76 doses) and 97% had at least 95% adherence (>79 doses). Adherence rates matched those seen in the C-EDGE treatment-naive and C-EDGE co-infected studies of non-injectors. There was no clear pattern of adherence over time, with the non-adherence rate rising at treatment weeks 4-6 and again at weeks 10-12.

Grazoprevir/elbasvir was safe and well-tolerated, with similar rates of serious adverse events (about 4%) and discontinuations (one each) in the active treatment and placebo arms. Most people reported some adverse events, but they occurred at least as often in the placebo group.

Dore did not report efficacy results, as participants are still in the 12-week post-treatment follow-up period need to determine sustained response. These findings will be presented at the AASLD American Liver Meeting in November.

The Kirby Institute will soon begin enrolling people who have recently injected drugs – who do not have to be on OST – into the SIMPLIFY study, testing Gilead's new coformulation containing sofosbuvir plus velpatasvir (GS-5816), which is active against HCV genotypes 1-6.

New York City study

Alain Litwin of Albert Einstein College of Medicine presented findings from a study of people on OST treated with sofosbuvir-based regimens.

This analysis looked at 61 participants who started hepatitis C treatment in an on-site opiate substitution treatment programme at three clinics in Manhattan, the Bronx and New Jersey. Just over 60% were men, 56% were Latino, 26% were black, 18% were white and the mean age was about 54 years. HCV genotypes 1, 2 and 3 were all well represented. Two-thirds were previously untreated and a quarter had cirrhosis.

Most participants (88%) were receiving methadone, with a smaller number taking buprenorphine. Two-thirds had used any illicit drugs within six months and 57% did so while on hepatitis C treatment. Nearly three quarters had psychiatric conditions, most often depression or anxiety. Almost all were on Medicaid, which provides health coverage for low-income people.

Most participants were treated with sofosbuvir plus ribavirin, though 12% also included pegylated interferon; 39% were treated for 12 weeks and the rest for 24 weeks. Participants and providers jointly decided whether to administer treatment one month at a time, one week at a time, or using directly observed therapy at the clinic.

The overall SVR12 rate was 80%. Sofosbuvir/ribavirin response rates were similar across genotypes, with interferon improving response. Again, these SVR rates were comparable to those seen in studies of non-injectors.

The researchers looked at several of measures of adherence, all of which decreased over time. Average daily adherence, for example, fell from 71% during weeks 1-12 of treatment to 61% during weeks 13-24. Adherence decreased somewhat with illicit drug use (though the change was not significant), but adherence and drug use were not associated with SVR in a multivariate analysis. Adherence did not differ based on monthly, daily or directly observed treatment administration.

“Rates of SVR are high in people who inject drugs initiating sofosbuvir-based regimens within an on-site HCV treatment program,” the researchers concluded. “Adherence (measured by electronic blister packs) is suboptimal but in this small study adherence was not associated with SVR. Adherence significantly decreased over [a] 24-week period, suggesting shorter courses of treatment [are] important in people who inject drugs.”

Active injection drug users

Finally, Arshia Alimohammadi of the Vancouver Infectious Diseases Centre described a study of hepatitis C treatment for active drug users on or off OST.

Although current AASLD, EASL and Canadian guidelines do not call for an abstinence period before initiating therapy, some providers follow the older practice of requiring six to twelve months without using drugs or alcohol, the researchers noted as background.

This retrospective observational study looked at 40 people receiving hepatitis C treatment between 2011 and 2015 at an inner city clinic while currently injecting drugs; 60% were on OST. Most (85%) were men and the median age was 53 years. A majority were previously untreated, about 60% had genotype 1, 25% had genotype 3, 28% had cirrhosis and 28% had HIV co-infection. About two-thirds received interferon-based therapy while the rest took all-oral regimens.

Overall, 78% of participants achieved SVR – 68% among those on interferon and 93% of those on interferon-free therapy. Similar SVR rates were seen for people using heroin (84%), cocaine (75%) and other stimulants (78%). Three people (8%) discontinued treatment due to side-effects. Over 1.5 years of post-treatment follow-up there have been no cases of HCV reinfection.

“Heavily active [people who inject drugs] can be effectively treated for HCV infection with high SVR rates,” the researchers concluded. “All-oral regimens are especially effective and will be an important tool of engagement in this population going forward.”

Benefits of treatment

Several presentations at the meeting looked at various models for providing hepatitis C treatment for people who inject drugs.

For example, the TAP (Treatment and Prevention) study in Australia encourages drug users to bring people in their injecting networks into treatment with them, which could curb post-SVR reinfection. The SToP-C (Surveillance and Treatment of Prisoners with hepatitis C) study is providing HCV testing and interferon-free treatment to inmates in Australian prisons. And in Vancouver’s Downtown Eastside, community pop-up clinics are bringing new people who inject drugs into care who have not made use of existing services.

The cost of new HCV therapies was a major topic throughout the meeting. High drug prices have led many government payers and private insurers to restrict treatment to the sickest patients, and in some cases to exclude people who have recently used drugs or alcohol.

Experts agreed, however, that hepatitis C treatment for people who inject drugs is likely to be cost-effective. Treatment can avert the long-term consequences of HCV infection such as liver cancer, decompensated cirrhosis and transplantation, thus saving healthcare resources down the road. In addition, people who are cured do not transmit HCV – a concept dubbed ‘treatment as prevention’ – which has the potential to halt local epidemics.

Ultimately, Jordan Feld concluded, “improved access [to treatment] is more important than improved therapy.”

The full INSHU program, with links to many of the presentations, is available online. Videos from the conference are available online through Conference Connect.

Journal special issue

Coinciding with the conference, the International Journal of Drug Policy launched its October 2015 special issue addressing hepatitis C among people who inject drugs, including recommendations for care and treatment. The guidelines encourage providers to offer treatment regardless of liver disease severity along with a comprehensive package of social support and harm reduction services. Other articles in the issue – which are free online – look at expanding access to prevention and treatment, liver disease progression, hepatitis C treatment as prevention and successful treatment models.


Feld J IFN-free therapy for HCV infection: In search of perfectovir. 4th International Symposium on Health Care in Substance Users, Sydney, 2015.

Dore G et al. C-EDGE CO-STAR: adherence and drug use in HCV-infected persons who inject drugs (PWID) on opioid agonist therapy (OAT) receiving grazoprevir + elbasvir (GZR/EBR) fixed dose combination (FDC) for 12 weeks. 4th International Symposium on Health Care in Substance Users, Sydney, 2015.

Litwin A et al. High rates of sustained virological response in people who inject drugs treated with sofosbuvir-based regimens. 4th International Symposium on Health Care in Substance Users, Sydney, 2015.

Grebely J et al. The single tablet regimen of ledipasvir/sofosbuvir is efficacious and well-tolerated among people receiving opioid substitution therapy. 4th International Symposium on Health Care in Substance Users, Sydney, 2015.

Alimohammadi A et al. Evaluation of HCV infection in active injection drug users. 4th International Symposium on Health Care in Substance Users, Sydney, 2015.