People who inject drugs are disproportionately affected by hepatitis C in Canada but have low rates of hepatitis C testing and treatment uptake. Data from 2017–2019 of the national Tracks survey of people who inject drugs in Canada (formerly I-Track) found that 64% of participants tested positive for hepatitis C antibodies, a measure of current or past infection.¹ Thirty-seven percent of participants were found to have a current hepatitis C infection. Among those with a current hepatitis C infection, only 50% were aware of their infection. Among those who were aware of their current hepatitis C infection, only 11% had ever been on hepatitis C treatment and only 4% were currently on treatment.

Additional strategies to increase access to hepatitis C testing and treatment among people who inject drugs are needed. This article summarizes a systematic review on the impact of opioid agonist therapy on hepatitis C testing and treatment for people who inject drugs.²

What is opioid agonist therapy?

Opioid agonist therapy (OAT) is used in the treatment of opioid dependence.³ It involves taking an oral opioid such as buprenorphine or methadone with the goal of improving a range of health outcomes, including reduced all-cause and drug-related mortality, reduced HIV and hepatitis C transmission, and improved quality of life.⁴ When people engage in OAT it can also provide an opportunity to improve access with other healthcare services. OAT has been found to improve engagement in HIV care and HIV treatment outcomes.⁵

What kind of research does the systematic review include?

The systematic review includes research on the association between using OAT and accessing hepatitis C testing and treatment among people who inject drugs.

Twenty-two studies were included in the review. A study was included if it:

• involved people with current drug use or recent drug use within the past 12 months
• reported on hepatitis C antibody or RNA testing, treatment uptake or treatment outcomes, including adherence, treatment completion and sustained virological response (SVR) (i.e., cure)
• compared the outcomes of people who had received OAT with those of people who had not received OAT (people who received OAT included people who had been on methadone or buprenorphine either ever or within the past six months, depending on the study)

Additional characteristics of the studies were as follows:

• They were published between 2008 and 2019. Studies on treatment completion were limited to studies involving direct-acting antiviral treatments published since January 2013.
• They took place in Australia (10 studies), Canada (4 studies), France (1 study), Georgia (1 study), Italy (1 study), Thailand (1 study), Ukraine (1 study) or the United States (2 studies).
• Together, the studies included approximately 22,000 participants.

Is opioid agonist therapy associated with hepatitis C testing uptake?

The review found a positive association between OAT and uptake of hepatitis C testing.

When looking at the impact of OAT on hepatitis C antibody testing, the review found the following:

• The proportion of people who had ever had a hepatitis C antibody test was between 33% and 94%. There was a significantly increased likelihood of ever having had a hepatitis C antibody test for both people who had ever been on OAT (odds ratio [OR] = 2.74 confidence interval [CI] 1.70, 4.40) and people who had recently used OAT (OR = 2.26 CI 1.80, 2.85).
• The proportion of people who had recently had a hepatitis C antibody test was between 48% and 71%. There was a significantly increased likelihood of recent hepatitis C antibody testing for both people who had ever been on OAT (OR = 2.12 CI 1.07, 4.20) and people who had recently used OAT (OR = 1.81 CI 1.40, 2.34).

When looking at the impact of OAT on hepatitis C RNA testing among people with hepatitis C antibodies, the review found the following:

• The proportion of people who had ever had a hepatitis C RNA test was between 35% and 89%. There was a significantly increased likelihood of ever having had a hepatitis C RNA test for both people who had ever been on OAT (OR = 2.14 CI 1.55, 2.95) and people who had recently used OAT (OR = 1.74 CI 1.29,2.35).
• The proportion of people who had recently had a hepatitis C RNA test was 44% in one study and 45% in a second study. There was a significantly increased likelihood of recent hepatitis C RNA testing for people who had recently used OAT (OR = 1.83 CI 1.28, 2.61). There was no association between recent RNA testing and ever receiving OAT.

Is opioid agonist therapy associated with hepatitis C treatment uptake?

The review found a positive association between OAT and uptake of hepatitis C treatment.

When looking at the association between OAT and ever having been on hepatitis C treatment among those who had been diagnosed with hepatitis C, the review found the following:

• The proportion of people who had ever been on hepatitis C treatment was between 6% and 72%. There was a significantly increased likelihood of ever having been on hepatitis C treatment for people who had recently used OAT (OR = 1.56 CI 1.07, 2.26). There was no association between ever having been on OAT and ever having been on hepatitis C treatment.
• When only studies conducted when direct-acting antiretroviral treatment was available were analyzed, the strength of the association between recent use of OAT and ever having been on hepatitis C treatment increased. There was a significantly increased likelihood of ever having been on hepatitis C treatment with direct-acting antivirals for people who had ever been on OAT (OR = 2.15 CI 1.67, 2.76).

Is opioid agonist therapy associated with completing hepatitis C treatment and sustained virological response?

The review did not find an association between OAT and hepatitis C treatment outcomes.

When looking at the association between OAT and completing treatment and SVR (cure) among those who had started hepatitis C treatment, the review found the following:

• The proportion of people who had completed hepatitis C treatment was between 65% and 100%. No association was found between recent use of OAT and completing hepatitis C treatment. The included studies did not examine the association between ever having been on OAT and completing hepatitis C treatment.
• The proportion of people who achieved SVR after treatment was between 64% and 94%. No association was found between recent use of OAT and SVR. The included studies did not examine the association between ever having been on OAT and SVR.

The review did not find an association between OAT and completing hepatitis C treatment or SVR (cure). The authors note that this is not surprising given that high rates of treatment completion and SVR have generally been found among people who inject drugs. For example, a systematic review (2018) found high SVR (cure) rates with treatment with direct acting antiretrovirals in people who use drugs or who are on OAT (88% and 91%, respectively).⁶

What are the implications of the review for service providers?

The evidence from this systematic review demonstrates that being on OAT can have a positive impact on hepatitis C testing and treatment uptake for people who inject drugs.

Making hepatitis C testing and treatment available to people on OAT, or integrating OAT and hepatitis C services may be potential ways to engage people who inject drugs in hepatitis C care. Receiving OAT provides opportunities for people to build relationships with care providers that can be beneficial to further engagement in hepatitis C care. Integration of OAT and hepatitis C services can also reduce barriers to accessing care.

When considering this review, it is important to remember the following:

The review looked at the association between OAT and hepatitis C testing and treatment and found a positive impact. It did not examine the factors that might have contributed to this association, such as how the services were delivered or the characteristics of the study participants. To better understand the association between OAT and hepatitis C testing and treatment, these facilitating factors should be taken into consideration.

The review did not find an association between OAT and completing hepatitis C treatment or SVR (cure). The authors note that this is not surprising given that high rates of treatment completion and SVR have generally been found among people who inject drugs whether they use OAT or not.

What is a systematic review?

Systematic reviews are important tools for informing evidence-based programming. A systematic review is a critical summary of the available evidence on a specific topic. It uses a rigorous process to identify all the studies related to a specific research question. Relevant studies can then be assessed for quality and their results summarized to identify and present key findings and limitations. If the studies included in a systematic review contain numerical data, these data can be combined in strategic ways to calculate summary (“pooled”) estimates. Pooled estimates can provide a better overall picture of the topic being studied. The process of pooling estimates from different studies is referred to as a meta-analysis.

References

1. Government of Canada. Tracks survey of people who inject drugs in Canada, Phase 4, 2017–2019: national findings. Canadian Communicable Disease Report; 2020 May 7; 46(11):138–48. Available from: https://www.canada.ca/en/public-health/services/reports-publications/can...
2. Grebely J, Tran L, Degenhardt L, Dowell-Day A, et al. Association between opioid agonist therapy and testing, treatment uptake, and treatment outcomes for hepatitis C infection among people who inject drugs: a systematic review and meta-analysis. Clinical Infectious Diseases. 2020; in press.
3. Harrigan, M. Opioid agonist therapy: Does it have a role to play in helping to prevent hepatitis C and HIV? Prevention in Focus. 2019 spring. Available from: https://www.catie.ca/en/pif/spring-2019/opioid-agonist-therapy-does-it-have-role-play-helping-prevent-hepatitis-c-and-hiv
4. Degenhardt L., Grebely J., Stone J., Hickman M., et al. Global patterns of opioid use and dependence: harms to populations, interventions, and future action. The Lancet. 2019; 394(10208): 1560-79. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068135.
5. Low AJ, Mburu G, Welton NJ, May MT, et al. Impact of opioid substitution therapy on antiretroviral therapy outcomes: a systematic review and meta-analysis. Clinical Infectious Diseases. 2016;63(8):1094–104.
6. Hajarizadeh B, Cunningham EB, Reid H et al. Direct-acting antiviral treatment for hepatitis C among people who use or inject drugs: a systematic review and meta-analysis. The Lancet. 2018;3(11):P754-767.