- There have been reports of people who use drugs being denied hepatitis C treatment
- Researchers studied offering treatment for hepatitis C and opioid dependency together
- 82% of participants were cured of hepatitis C, and drug use was not a significant factor
Opioid use disorder and ongoing contamination of the drug supply with fentanyl and related compounds underpin the continued high number of overdoses reported in North America. Injecting drugs also carries a range of harms related to infectious diseases, such as HIV and hepatitis C virus (HCV) as well as serious bacterial and fungal infections.
In an article in press in the journal Clinical Infectious Diseases, a team of scientists at the U.S. National Institutes of Health (NIH) reports that some insurance companies, jurisdictions and care providers may choose not to facilitate or provide HCV-related care to people with opioid use disorder “due to concerns about the ability to adhere to daily medication and risks for reinfection.” Given the high interest in HCV treatment among people who inject drugs, offering HCV treatment can serve as an opportunity not only to cure HCV but also to engage people in care and offer them an array of harm reduction services including opioid substitution therapy.
Although the long-term health risk from HCV infection is high, the NIH scientists stated that “even more pressing may be risks associated with drug use, including overdose death.” Opioid substitution therapy, including medicines such as buprenorphine and methadone, is one of several approaches that can contribute to a reduced risk of overdose-related death. The NIH scientists made this critical point about the way substance use is viewed by some care providers: “Rather than viewing baseline opioid use as non-modifiable, it is important to consider HCV treatment as a method to engage patients in [opioid substitution therapy], and understand how concurrent treatment may affect both drug use and HCV outcome.”
The Anchor study
In a clinical trial called Anchor, scientists at the University of Maryland and the NIH collaborated with a harm reduction organization in Washington, DC. The collaboration involved offering buprenorphine, care and HCV treatment to people with opioid use disorder and monitoring the results.
The scientists found that, overall, 82% of participants were cured of HCV infection. This rate of cure was largely not affected by substance use. Engagement with opioid substitution therapy significantly reduced the rate of substance use and opioid overdoses.
The Anchor study confirms research from Canada, Australia and other countries that shows that providing opioid substitution therapy together with HCV treatment and other services can result in high rates of HCV cure and reduce the harms associated with injecting drugs.
Community workers recruited 100 participants for Anchor, which took place at a drop-in centre run by a harm reduction organization. The organization provided the following:
- sterile needles/syringes
- laundry facilities
- housing assistance
- testing for HIV and HCV
- HIV case management
Community workers liaised with participants and provided HCV treatment—a pill called Epclusa (sofosbuvir + velpatasvir), taken once daily for 12 consecutive weeks.
The average profile of participants, all of whom had opioid use disorder, was as follows:
- 76% men, 24% women
- age – 58 years
- HCV + HIV co-infection – 3%
- 33% had extensive liver injury (cirrhosis)
- most participants (93%) had a strain of HCV called genotype 1
- 51% had unstable housing
- at least 50% of participants did not have a stable source of income
- 92% had previously been imprisoned
- most participants began injecting street drugs at the age of 21
- 60% injected drugs at least once daily
- 18% were enrolled in a syringe exchange program
- 33% were receiving opioid substitution therapy
Participants were evaluated at regular intervals. Sofosbuvir-velpatasvir was prescribed once daily for 12 consecutive weeks and participants were monitored for a further 12 weeks. The drug was dispensed in bottles containing 28 pills, one bottle every four weeks.
Participants who were not on opioid substitution therapy at the start of the study were offered buprenorphine and naloxone (in case of overdose) .
Participants provided urine samples at regular intervals for analysis of exposure to street drugs.
A total of 82 participants (82%) were cured of HCV. The distribution of the remaining participants was as follows:
- 11 people – relapse of HCV infection (when a person has an undetectable viral load at the end of treatment and then has a detectable viral load 12 weeks later)
- 3 people – ceased contact with the study site
- 3 people – died
- 1 person – imprisoned
Factors associated with achieving a cure were as follows:
- being on opioid substitution therapy by the end of the study (by this time, 68% of participants were on opioid substitution therapy)
- consuming at least two bottles of sofosbuvir-velpatasvir over the course of the study
Among participants who were not initially taking opioid substitution therapy at the start of the study, rates of HCV cure were higher when they subsequently initiated opioid substitution therapy and remained on this therapy.
Analysis at the start of the study detected opioids in urine samples from 90% of participants. Also, urine samples tested positive for cocaine in 61% of cases.
Once participants began to take HCV treatment and opioid substitution therapy, scientists found a significant decline in the rate of substance use. This decline was sustained throughout the study.
A total of 84% of participants took all three bottles of sofosbuvir-velpatasvir.
Sixteen participants (16%) disclosed that they interrupted their HCV treatment, usually for about nine days.
Thirteen participants (13%) experienced at least one overdose during the study, two of whom died. According to reports from the medical examiner, the substances involved in these deaths were as follows:
- fentanyl + alprazolam (Xanax) + alcohol
The distribution of overdoses was as follows:
- not taking opioid substitution therapy – 8 people (26% of those not taking buprenorphine)
- taking opioid substitution therapy – 5 people (7% of those taking buprenorphine)
The Anchor study showed that when opioid substitution therapy and HCV treatment are offered in the same location, many people are willing to use both and can do so successfully. The scientists stated that the relatively high rate of HCV cure was “not significantly associated with ongoing drug use, including injection drug use, similar to previous studies of people who use drugs.”
The study did not provide adherence support, as the scientists sought to replicate conditions in the everyday world of HCV treatment. While there were some treatment interruptions, cure rates were relatively high. Rates of cure were similarly high in people who entered the study already on opioid substitution therapy (92%) and in people who initiated such therapy during the study and remained on it by the end of the study (93%). The researchers stated that “this argues against the need for a period of abstinence or stabilization on [opioid substitution therapy], and reinforces the fact that welcoming patients into HCV care may foster a therapeutic relationship which can be leveraged to engage patients in treatment for opioid use disorder. Denying patients HCV treatment until they engage in drug treatment, on the other hand, may serve to reinforce distrust in the medical community and result in loss of engagement for both HCV and opioid use disorder treatment.”
No one working on the study had extensive training in addiction medicine. The scientists underscored that if progress against the overdose crisis is to be made, reliance on “non-addiction specialists” will be needed.
An interesting aspect of the study was the cooperation between medical care providers (specialists in infectious diseases, internal medicine and nursing) and community workers. The scientists stated that “the Anchor model provides a blueprint for how to access this marginalized population and initiate collocated care in a way that can ultimately facilitate HCV elimination.”
Given that there are variations in the mix of substances used across the continent, the scientists stated that it would be “valuable to replicate this model in other demographic populations”—including people who use opioids and methamphetamine—and to deploy additional forms of opioid substitution therapy (methadone, buprenorphine injections, naltrexone).
The results from Anchor support results from studies in Canada, Australia, Austria and other countries where clinics and organizations have provided a combination of harm reduction services and HCV treatment to people who inject drugs. In some of those studies, other HCV treatments such as Harvoni (ledipasvir + sofosbuvir), Maviret (glecaprevir + pibrentasvir) and Zepatier (elbasvir + grazoprevir) were also highly effective in curing people.
Hepatitis C treatment in harm reduction programs for people who use drugs – Prevention in Focus
Epclusa (velpatasvir + sofosbuvir) – CATIE factsheet
Harvoni (ledipasvir + sofosbuvir) – CATIE factsheet
Maviret (glecaprevir + pibrentasvir) – CATIE factsheet
Zepatier (elbasvir + grazoprevir) – CATIE factsheet
—Sean R. Hosein
- Rosenthal ES, Silk R, Mathur P, et al. Concurrent initiation of hepatitis C and opioid use disorder treatment in people who inject drugs. Clinical Infectious Diseases. 2020; in press.
- Springer SA, Del Rio C. Co-located opioid use disorder and HCV treatment is not only right but it is also the smart thing to do as it improves outcomes! Clinical Infectious Diseases. 2020; in press.
- Coffin PO, Santos GM, Behar E, et al. Randomized feasibility trial of directly observed versus unobserved hepatitis C treatment with ledipasvir-sofosbuvir among people who inject drugs. PLoS One. 2019;14(6):e0217471.
- Grebely J, Dore GJ, Alami NN, et al. Safety and efficacy of glecaprevir/pibrentasvir in patients with chronic hepatitis C genotypes 1-6 receiving opioid substitution therapy. International Journal on Drug Policy. 2019;66:73–79.
- Blumenkrans E, Socías ME, Richardson L, et al. Longitudinal factors associated with used syringe lending among HIV-positive antiretroviral therapy-naïve people who inject drugs in a Canadian setting. AIDS and Behavior. 2020; in press.
- Schütz A, Moser S, Schwanke C, et al. Directly observed therapy of chronic hepatitis C with ledipasvir/sofosbuvir in people who inject drugs at risk of nonadherence to direct-acting antivirals. Journal of Viral Hepatitis. 2018;25(7):870–873.
- Janjua NZ, Darvishian M, Wong S, et al. Effectiveness of ledipasvir/sofosbuvir and sofosbuvir/velpatasvir in people who inject drugs and/or those in opioid agonist therapy. Hepatology Communications. 2019;3(4):478–492.
- Dore GJ, Altice F, Litwin AH, et al. Elbasvir-grazoprevir to treat hepatitis C virus infection in persons receiving opioid agonist therapy: A randomized trial. Annals of Internal Medicine. 2016;165(9):625–634.