Opioid agonist therapy: Does it have a role to play in helping to prevent hepatitis C and HIV?

Prevention in Focus PiF 2019 Spring

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Opioid use is associated with hepatitis C and HIV transmission and overdose, among other harms. Opioid agonist therapy (OAT) is an effective treatment for opioid use disorder and helps to address drug-related harms including lowering the risk of hepatitis C and HIV. There are several medications that can be used as OAT in Canada, including methadone, buprenorphine, hydromorphone and prescription heroin. This article will review evidence showing the benefits of OAT and review some ways to facilitate better access in Canada.

Opioid use in Canada

In light of the national overdose crisis, opioid use is increasingly being recognized as a major public health priority in Canada that requires immediate action. Opioid drugs are an effective short-term strategy to manage acute pain but long-term use can lead to reduced effectiveness in reducing pain and increased risk of serious adverse events. Opioids are highly addictive, which can lead to a person using their own opioid medication in a way that was not prescribed (for example, taking larger doses than prescribed) or injecting drugs that are intended to be swallowed. Opioids can also be obtained from someone else who has a prescription, or they can be bought in the unregulated market in the form of powder or powder pressed into pills.  

Opioids can be taken in a number of ways, such as being swallowed in pill form, inhaled through the nose as a powder, smoked or injected. Injection is generally considered the most harmful way to take opioids, because it carries a higher risk of overdose, HIV, hepatitis C and other infections.1,2

One in every five Canadians (22%) who participated in a 2017 online survey conducted by Health Canada reported taking opioids at some point in the past year.3 Of these, 31% reported that they didn’t always have a prescription for the opioids they used. This means that in the past year 7% of respondents had used opioids that were not prescribed to them. While this doesn’t provide a full picture of opioid use disorder in Canada it does provide a glimpse into how frequently Canadians are using opioids.

Potential harms associated with opioid use

While not all opioid use causes harms, there are a number of potential harms associated with opioid use, whether the drugs are injected or consumed in another way. The most immediate concern with opioid use is the risk of fatal overdose. Canada is currently experiencing an overdose crisis. From January 2016 to June 2018 there were over 9,000 apparent opioid-related deaths in Canada.4 Many of these deaths occurred after a person used drugs acquired from the unregulated market that were of unknown content. These drugs often contain mixes of toxic opioids such as fentanyl analogues including highly dangerous carfentanil.4

Depending on how a person takes opioids, there may also be a risk of hepatitis C and HIV transmission. Sharing injection equipment carries the highest risk of transmission for both hepatitis C and HIV because the viruses can be introduced directly into the bloodstream.1 According to the most recent estimates available, 42.6% of all hepatitis C antibody-positive cases5 and 14.3% of all new HIV infections6 in Canada may have been acquired through injection drug use. Hepatitis C may also be passed through sharing equipment used to smoke drugs.1,7

When a person becomes dependent on opioids, they experience severe withdrawal symptoms when not taking opioids.8,9 This dependence often interferes with their ability to carry out activities in their normal life, including work and family commitments, and increases their chance of being involved in sex work or other illegal activity in order to obtain opioids. Long-term opioid use also comes with an increased risk of various physical and mental health issues.8,9

What is opioid agonist therapy and how does it work?

Opioid agonist therapy (OAT), also called opioid substitution therapy, is the gold standard for the treatment of opioid use disorder and a key strategy to reduce the harms of opioid use disorder by providing structured access to long acting opioids to improve stability and day-to-day function.10 OAT medications are legal, and they are prescribed by a health care provider to help manage withdrawal symptoms and drug cravings. They are taken by people who want to reduce or eliminate their use of illicit opioids. There are two types of OAT: oral and injectable.

Oral OAT with methadone or buprenorphine

In Canada, the most commonly available forms of OAT are methadone or buprenorphine.10 Methadone is a drug that is also sometimes prescribed for pain management. Methadone and buprenorphine are long-acting opioids that work by activating the opioid receptors in a person’s brain. These are the same receptors that other opioids such as heroin activate. When opioid receptors are activated, they release dopamine. Drugs such as heroin cause the receptors to release a large amount of dopamine at one time, causing a euphoric (high) feeling. People who are dependent on opioids experience withdrawal symptoms after the drug wears off and leaves the opioid receptors. When taken orally and at the right dose, the drugs used for oral OAT do not cause enough dopamine to be released at one time to give a euphoric (high) feeling; however, they do cause enough dopamine to be released to manage withdrawal symptoms. Oral OAT medications can help to manage withdrawal symptoms for a full day because they are long-acting. Both methadone and buprenorphine are taken orally once per day. Some people choose to take oral OAT indefinitely, while others take it with the intention of eventually getting off OAT. This is done by slowly reducing the dose over time ensuring that the person does not experience undue distress or begin supplementing drugs. This process is known as tapering.

Methadone, sold under the brand name Methadose, is a liquid. When a person first starts taking methadone, they need to be observed taking it each day. This is often done at a pharmacy where a pharmacist can watch the person take their dose, or it can be done at a hospital or medical clinic. The reason that people are observed is to reduce the chance of methadone being misused (for example, injected or given to others). Over time, some people may be able to take some doses home so that they do not need to come into a pharmacy or clinic every day.10

Canadian guidelines recommend that people taking buprenorphine take a drug which contains buprenorphine as well as another drug called naloxone.10 In Canada, this drug is sold under the brand name Suboxone. Suboxone is a pill that is dissolved under a person’s tongue. When Suboxone is dissolved under the tongue as intended, buprenorphine reaches the opioid receptors in a person’s brain, and naloxone has no effect. This is because naloxone has a low bioavailability when taken under the tongue, meaning that only a very small amount of the drug can make its way to the brain when taken this way. Naloxone is included in Suboxone to discourage people from misusing the drug. If Suboxone is injected or inhaled through the nose, naloxone will make its way to the brain, where it will block the effect of buprenorphine and any other opioids in the person’s system. Because Suboxone can’t easily be misused, after the first week or two most people no longer need to be directly observed and they can take doses at home.10

In some cases slow-release morphine can also be prescribed as oral OAT, but this is fairly rare.10 Morphine can be considered when methadone and buprenorphine are either ineffective or contraindicated for a patient. Morphine has not been studied as thoroughly as buprenorphine and methadone for use as an oral OAT medication.

Injectable OAT with hydromorphone or prescription heroin

Supervised injectable OAT is an alternative to oral OAT that involves taking injectable medications in a supervised environment. The drugs used for this type of OAT are hydromorphone and prescription heroin (diamorphine/diacetylmorphine). These alternatives to oral OAT may be more effective for people who have been using opioid drugs for a long time and who have tried oral OAT unsuccessfully.11,12 These drugs act for a shorter time than oral OAT. They cause the euphoric (high) feeling that a person would get from using street-obtained opioids such as heroin. Injectable OAT is considered a safer option than street-obtained opioids because the medications are regulated so doses are consistent and they are not cut with other harmful substances, such as fentanyl.13 A person taking injectable OAT injects the drug themselves under the supervision of a medical professional, who can respond to overdoses and other medical issues if necessary.13

Injectable OAT is not used as commonly as oral OAT and Canada does not currently have national clinical guidelines for injectable OAT. However, British Columbia has developed guidelines.13 The guidelines recommend that people who take injectable OAT receive these medications up to three times per day. They also recommend that people should be offered oral OAT such as methadone or morphine as part of their care, if they want to reduce the amount of injectable drugs that they are taking, or to help them to manage withdrawal symptoms between doses. For example, a person may choose oral OAT rather than injectable OAT for their last dose of the day to manage withdrawal symptoms overnight.

How well does OAT work for reducing illicit opioid use?

Research has consistently shown that oral OAT using buprenorphine or methadone helps to reduce illicit opioid use. A meta-analysis of six randomized controlled trials found that people taking methadone maintenance therapy were 34% less likely to test positive for heroin metabolites than people who did not receive OAT.14 A more recent review noted that methadone is most effective at reducing illicit opioid use when given at doses higher than 60 mg.15 Meta-analyses have shown that buprenorphine is roughly as effective as methadone at reducing illicit opioid use.16,17

Several studies have shown that prescription heroin is effective at reducing opioid use among long-term heroin users. A systematic review looked at six randomized trials that measured outcomes for people taking prescription heroin in a supervised setting (some of whom also received doses of methadone), compared with people who were receiving only oral methadone.[fan value=11] The studies measured opioid use in different ways so their results could not be combined, but each study reported that prescription heroin treatment significantly reduced opioid use.11 The largest of these studies randomly assigned 1,015 people to receive either prescription heroin or oral methadone.18 At the 12-month follow-up, 69% of people in the prescription heroin group reduced their illicit drug use (measured by either biological tests or self-reported drug use), compared with only 55% of those in the methadone group.

So far only one study has looked at injectable hydromorphone as OAT. This randomized trial in Vancouver compared long-term heroin users who were taking prescription heroin with those taking hydromorphone.12 Those who received injectable hydromorphone reported on average 4.34 days of street opioid use in the previous month, and those who took prescription heroin reported on average 4.20 days in the previous month. This difference was not statistically significant, so the researchers concluded that hydromorphone was as effective as prescription heroin.

How well does OAT help to prevent hepatitis C and HIV transmission?

Oral and injectable OAT play a key role in helping to prevent the spread of hepatitis C and HIV. People who are taking oral OAT have been found to reduce sharing of injection drug use equipment, thereby reducing their risk of hepatitis C and HIV.  Injectable OAT is taken in a supervised environment where new equipment is provided for each injection and medical staff can ensure that equipment is not shared. Therefore, people taking injectable OAT are only at risk if they are using other drugs outside the clinic and share drug equipment when doing so.

Oral OAT

A systematic review looked at needle and syringe sharing among people taking oral OAT, as measured by 19 studies.19 Sixteen of those studies found that oral OAT was associated with reduced needle sharing. There is evidence that OAT also reduces the transmission of hepatitis C and HIV in a number of other ways, such as by lowering risky sexual behaviour, improving adherence to treatment in people who have HIV or hepatitis C and engaging people in healthcare.20,21,22

A number of studies have looked directly at the connection between oral OAT and the incidence of hepatitis C and HIV. A meta-analysis found that taking oral OAT with either buprenorphine or methadone may reduce the risk of getting hepatitis C by 50%.23 Similarly, another meta-analysis found that taking methadone was associated with a 54% reduced risk of getting HIV among people who inject drugs.24

Studies have noted factors that contribute to the effectiveness of oral OAT in reducing the risk of hepatitis C and HIV. Research shows oral OAT is most successful when provided at a high enough dose and when combined with other harm reduction options and supports. For example, the meta-analysis that showed that oral OAT was associated with a 50% reduction in hepatitis C incidence also found that this number increased to 74% when oral OAT was combined with a needle syringe program.23 The Canadian guideline for the management of opioid use disorders recommends that psychosocial supports be offered along with oral OAT to maximize its effectiveness, though the guideline stresses that these interventions should not be mandatory for people who want to access OAT.10

Injectable OAT

It hasn’t been possible for studies to directly measure whether the incidence of hepatitis C and HIV is reduced in people using injectable OAT treatments, because most studies looking at injectable OAT have had a fairly small number of participants. Two small studies have looked at hepatitis C and HIV risk behaviours in people taking prescription heroin. One of these studies compared the number of people who shared injection materials before and after starting treatment.25 Of the 27 people who were registered to receive treatment, 44% (12) reported sharing injection equipment in the six months before treatment, and only 4% (one) reported doing so in the first six months on treatment (this person participated in the study but did not show up to receive treatment). The other study used a standardized scale to measure drug-related HIV risk behaviours before and after starting prescription heroin treatment.26 The study found that the average score was 8.9 out of 30 before starting treatment and 0.6 after nine months of treatment, which was a significant reduction in risk. These findings suggest that it is likely that the reduction in risk behaviour helps to prevent hepatitis C and HIV transmission.

What is the state of OAT access in Canada?

Oral OAT has long been approved in Canada as an effective treatment for people who are dependent on opioids. The first drug to receive approval was methadone, which was approved by Health Canada in 1959. However, access is not universal. Each province and territory is in charge of running its own oral OAT programs, so the resources allocated to oral OAT and procedures for accessing it vary considerably. In many parts of the country there are more people wanting to start oral OAT than the programs’ resources can accommodate, and it is common for people to be put on a waitlist. Access to oral OAT is often particularly challenging for people who live in rural and remote areas.27

Injectable OAT is not used as widely as oral OAT in Canada. Outside of clinical trials, prescription heroin is currently not easily available in Canada. Doctors who want to prescribe the drug must apply for permission through a federal special access program. In contrast, hydromorphone can be prescribed off-label, as it is already approved for use in pain management; however, accessibility is limited in Canada.  

In May 2018, the federal government amended the Controlled Drugs and Substances Act in an effort to make OAT more easily accessible. Before this amendment, doctors were required to apply for an exemption to be able to prescribe methadone, and pharmacies needed to apply for an exemption to administer it. This requirement has been lifted and methadone can now be prescribed by any doctor and administered by any licensed pharmacist. The amendment also includes changes that improve access to prescription heroin. Most notably, it allows prescription heroin to be administered outside of a hospital setting.

What can service providers do to help more people to access OAT?

Service providers and community advocates play an important role in expanding access to OAT. Service providers can work with clients to facilitate access. This can be done by educating people who have an opioid use disorder about the types of OAT available and the benefits and limitations of OAT options in the community. This information should always be provided alongside information about other harm reduction options that are available locally, such as needle and syringe programs, supervised consumption services and overdose prevention sites. Service providers can refer clients who express an interest in OAT to a doctor or nurse practitioner and help them to find a suitable place to receive doses of their medication. Some clients may also require support to adhere to medications.

Advocates can also work to make OAT more accessible in their region. This might include working with doctors and pharmacists to develop OAT programs. It might also include engaging with regulators at various levels of government to advocate for improved funding or changes to regulations to make OAT accessible to more people. Access can be especially difficult for some populations, such as for people who are incarcerated and pregnant women. Advocacy may be needed to develop capacity to deliver OAT to people who face unique challenges.

Resources

Management of opioid use disorders: a national clinical practice guideline - CMAJ

Opiate agonist therapy: Information for clients – Centre for Addiction and Mental Health (camh)

Injectable Opioid Agonist Treatment for Opioid Use Disorder – BC Centre on Substance Use (BCSU)

Evidence brief: Effectiveness of supervised injectable opioid agonist treatment (siOAT) for opioid use disorder – Public Health Ontario

Special Access Programme – Drugs – Health Canada

Regulations Amending the Narcotic Control Regulations and the New Classes of Practitioners Regulations (Diacetylmorphine (Heroin) and Methadone): SOR/2018-37 – Government of Canada

 

References

  1. a. b. c. Strike C, Hopkins S, Watson TM et al. Best Practice Recommendations for Canadian Harm Reduction Programs that Provide Service to People Who Use Drugs and Are at Risk for HIV, HCV, and Other Harms: Part 1. Toronto: Working Group on Best Practice for Harm Reduction Programs in Canada; 2013. Available from: http://www.catie.ca/sites/default/files/BestPracticeRecommendations_HarmReductionProgramsCanada_Part1_August_15_2013.pdf
  2. Health Canada. Opioid overdose. Ottawa; 2018. Available from: https://www.canada.ca/en/health-canada/services/substance-use/problematic-prescription-drug-use/opioids/overdose.html#a1
  3. Earnscliffe Strategy Group. Baseline Survey on Opioid Awareness, Knowledge and Behaviours for Public Education Research Report. Ottawa; 2017. Available from: http://epe.lac-bac.gc.ca/100/200/301/pwgsc-tpsgc/por-ef/health/2018/016-17-e/report.pdf
  4. a. b. Special Advisory Committee on the Epidemic of Opioid Overdoses. National Report: Apparent Opioid-related Deaths in Canada (released December 2018) [web-based report]. Ottawa: Public Health Agency of Canada; 2018 Sept. Available from: https://infobase.phac-aspc.gc.ca/datalab/national-surveillance-opioid-mortality.html
  5. Trubnikov M, Yan P, Archibald C. Estimated prevalence of hepatitis C virus infection in Canada, 2011. Canada Communicable Disease Report 2014 Dec 18;40(19):429-36. Available from: http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/14vol40/dr-rm40-19/surveillance-b-eng.php
  6. Public Health Agency of Canada. Summary: Estimates of HIV Incidence, Prevalence and Canada’s Progress on Meeting the 90-90-90 HIV targets, 2016. Ottawa: Public Health Agency of Canada; 2017. Available from: https://www.canada.ca/en/public-health/services/publications/diseases-conditions/summary-estimates-hiv-incidence-prevalence-canadas-progress-90-90-90.html.
  7. Strike C, Watson TM, Gohil H et al.  Best Practice Recommendations for Canadian Harm Reduction Programs that Provide Service to People Who Use Drugs and Are at Risk for HIV, HCV, and Other Harms: Part 2. Toronto: Working Group on Best Practice for Harm Reduction Programs in Canada; 2015. Available from: http://www.catie.ca/sites/default/files/bestpractice-harmreduction-part2.pdf
  8. a. b. National Institute on Drug Abuse. Research Report Series: Heroin. Bethesda, MD: National Institutes of Health; 2014. Available from: https://www.drugabuse.gov/sites/default/files/heroinrrs_11_14.pdf
  9. a. b. Canadian Centre on Substance Use and Addiction. Prescription Opioids. Ottawa: Canadian Centre on Substance Use and Addiction; 2017. Available from: http://www.ccsa.ca/Resource%20Library/CCSA-Canadian-Drug-Summary-Prescription-Opioids-2017-en.pdf
  10. a. b. c. d. e. f. g. Bruneau J, Ahamad K, Goyer MÈ et al. Management of opioid use disorders: a national clinical practice guideline. Canadian Medical Association Journal. 2018 Mar 5;190(9):E247-57.
  11. a. b. Strang J, Groshkova T, Uchtenhagen A et al. Heroin on trial: systematic review and meta-analysis of randomised trials of diamorphine-prescribing as treatment for refractory heroin addiction. The British Journal of Psychiatry. 2015;207(1):5-14.
  12. a. b. Oviedo-Joekes E, Guh D, Brissette S et al. Hydromorphone compared with diacetylmorphine for long-term opioid dependence: a randomized clinical trial. JAMA Psychiatry. 2016 May 1;73(5):447-55.
  13. a. b. c. British Columbia Centre on Substance Use. Guidance for Injectable Opioid Agonist Treatment for Opioid Use Disorder. Vancouver: British Columbia Centre on Substance Use, Ministry of Health; 2017.
  14. Mattick RP, Breen C, Kimber J et al. Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Cochrane Database of Systematic Reviews. 2009 Jul 8;(3):CD002209.
  15. Fullerton CA, Kim M, Thomas CP et al. Medication-assisted treatment with methadone: assessing the evidence. Psychiatric Services. 2014 Feb;65(2):146-57.
  16. Thomas CP, Fullerton CA, Kim M et al. Medication-assisted treatment with buprenorphine: assessing the evidence. Psychiatric Services. 2014 Feb;65(2):158-70.
  17. Nielsen S, Larance B, Degenhardt L et al. Opioid agonist treatment for pharmaceutical opioid dependent people. Cochrane Database of Systematic Reviews. 2016 May 9;(5):CD011117
  18. Haasen C, Verthein U, Degkwitz P et al. Heroin-assisted treatment for opioid dependence: randomised controlled trial. British Journal of Psychiatry. 2007 Jul;191(1):55-62.
  19. MacArthur GJ, van Velzen E, Palmateer N et al. Interventions to prevent HIV and hepatitis C in people who inject drugs: a review of reviews to assess evidence of effectiveness. International Journal of Drug Policy. 2014 Jan 1;25(1):34-52.
  20. Gowing LR, Hickman M, Degenhardt L. Mitigating the risk of HIV infection with opioid substitution treatment. Bulletin of the World Health Organization. 2013;91:148-9.
  21. Karki P, Shrestha R, Huedo-Medina TB et al. The impact of methadone maintenance treatment on HIV risk behaviors among high-risk injection drug users: a systematic review. Evidence-based Medicine & Public Health. 2016;2. pii: e1229.
  22. Perlman DC, Jordan AE, Uuskula A et al. An international perspective on using opioid substitution treatment to improve hepatitis C prevention and care for people who inject drugs: structural barriers and public health potential. International Journal of Drug Policy. 2015 Nov 1;26(11):1056-63.
  23. a. b. Platt L, Minozzi S, Reed J et al. Needle syringe programmes and opioid substitution therapy for preventing hepatitis C transmission in people who inject drugs. Cochrane Database of Systematic Reviews. 2017;9:CD012021.
  24. MacArthur GJ, Minozzi S, Martin N et al. Opiate substitution treatment and HIV transmission in people who inject drugs: systematic review and meta-analysis. BMJ. 2012 Oct 4;345:e5945.
  25. Perneger TV, Giner F, del Rio M et al. Randomised trial of heroin maintenance programme for addicts who fail in conventional drug treatments. BMJ. 1998 Jul 4;317(7150):13-8.
  26. March JC, Oviedo-Joekes E, Perea-Milla E et al. Controlled trial of prescribed heroin in the treatment of opioid addiction. Journal of Substance Abuse Treatment. 2006 Sep 1;31(2):203-11.
  27. Eibl JK, Morin K, Leinonen E et al. The state of opioid agonist therapy in Canada 20 years after federal oversight. Canadian Journal of Psychiatry. 2017 Jul;62(7):444-50.

 

About the author(s)

Mallory Harrigan is CATIE's Knowledge Specialist, HIV Prevention. She has a Master's degree in Community Psychology from Wilfrid Laurier University.