Research paperInitiating HCV treatment with direct acting agents in opioid agonist treatment: When to start for people co-infected with HIV?
Introduction
Hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality, affecting approximately 71.1 million individuals, globally (The Polaris Observatory HCV Collaborators, 2017). In high income countries, most new HCV infections occur among people who inject drugs (PWID), with an estimated incidence of 2–46 infections per 100 person-years (Backmund, Reimer, Meyer, Gerlach, & Zachoval, 2005; Folch et al., 2016, Grebely and Dore, 2011; Hajarizadeh, Grebely, & Dore, 2013; Maher, Li, Jalaludin, Chant, & Kaldor, 2007; Page, Morris, Hahn, Maher, & Prins, 2013; van den Berg et al., 2007). While PWID are disproportionately burdened by HCV (prevalence ranging from 60% to 80%), almost half are unaware of their status (Nelson et al., 2011).
The development of simpler, more tolerable and highly effective direct acting antiviral (DAA) agents has generated optimism for the eradication of HCV (Kardashian & Pockros, 2015). Recent modelling exercises demonstrate that HCV prevalence can be reduced considerably if treatment is scaled-up and targeted to PWID, (Grebely and Dore, 2014, Hellard et al., 2014, Martin et al., 2015, Martin et al., 2013) and international recommendations support HCV treatment with DAA therapy for PWID (Grebely et al., 2015). However, concerns regarding suboptimal adherence to HCV treatment, treatment failure, or subsequent reinfection (Grebely, Oser, Taylor, & Dore, 2013; Harris & Rhodes, 2013; Myles, Mugford, Zhao, Krahn, & Wang, 2011) coupled with restrictions on HCV treatment eligibility pertaining to substance use, (Barua et al., 2015) constrain the impact of new DAA therapies among PWID.
Integrating HCV treatment with opioid agonist treatment (OAT) is a promising strategy to engage and retain PWID with DAA therapy (Keats et al., 2015; Treloar, Newland, Rance, & Hopwood, 2010). Improving outcomes by integrating OAT with HIV care is well established (Low et al., 2016) and the 2016 Recommendations of the International Antiviral Society-USA Panel encourage OAT to help improve antiretroviral (ART) adherence among PWID (Günthard et al., 2016). Similar observational findings of HCV treatment compliance in OAT settings are currently lacking (Taylor, Swan, & Matthews, 2013) and OAT remains highly restricted in many settings (Des Jarlais, Arasteh, & Gwadz, 2010; Mathers et al., 2008). However, qualitative research from the Enhanced Treatment for Hepatitis C in Opioid Substitution Settings (ETHOS) prospective observational study in Australia, has demonstrated staff and clients welcome the integration of HCV services into OAT settings, citing the benefits of pre-existing relationships, reduced travel time and costs, recurring opportunities for engagement, and immediacy of care available (Treloar, Rance, & ETHOS Study Group, 2014; Treloar, Rance, Grebely, & Dore, 2013).
The successful integration of HCV treatment in OAT for PWID will be contingent on clinicians initiating HCV courses at a time-point when patients are likely to be retained in OAT for at least twelve weeks. Population-level observational studies demonstrate that although OAT is characterized by frequent treatment interruptions (Marcovitz, McHugh, Volpe, Votaw, & Connery, 2016; Nosyk et al., 2009), treatment retention in OAT improves over successive attempts (Marcovitz et al., 2016, Nosyk et al., 2009), thereby offering an opportunity to engage PWID with DAA therapy. However, it remains unclear what the optimal time point is at which DAA can be initiated following OAT initiation, and how this time-point may differ across sub-groups of PWID.
Efforts to identify the optimal start time for DAA are complicated by the limited number of PWID concurrently receiving OAT and DAA, making it difficult to directly observe HCV treatment and retention. DAAs are increasingly being added to insurance drug formularies internationally, but remain out of reach for most PWID (Barua et al., 2015). For example, although DAAs were added to British Columbia’s provincial PharmaCare drug insurance formulary in 2015, (Pacific Hepatitis C Network, 2016) and drug use or HIV co-infection do not preclude eligibility for treatment, physicians can restrict access to patients that appear to be at high-risk for non-compliance (Marshall et al., 2016).
However, OAT retention can provide indirect evidence for potential DAA treatment adherence among HCV-infected PWID, either engaged or not engaged in other forms of treatment. While we currently lack population-level data for the entire HCV-infected population of PWID, we may examine OAT retention using linked population-level data available for British Columbia on HIV/HCV co-infected populations initiating OAT. Using this data, we undertook this study to identify when OAT adherence sufficiently improved to inform DAA initiation in OAT settings, assuming continuous OAT retention for at least twelve weeks is necessary to complete a DAA treatment course.
Section snippets
Design
We used a population-level retrospective cohort of HIV/HCV co-infected PWID in British Columbia (BC), Canada. The cohort was followed in a unique environment wherein all antiretroviral medications, and approximately 85% of OAT expenses (e.g. physician, drug dispensing, medication and counselling fees) were covered by the province’s universal PharmaCare insurance. In fiscal year 2013/14, PharmaCare paid $46 million of the $53 million (CAD) associated with OAT, while private insurance and
Results
Our cohort included 1427 HIV/HCV co-infected PWID who initiated at least one OAT episode after HIV diagnosis. The cohort had a median number of two OAT episodes per person (IQR = 1–4) for a total of 4062 episodes and 38,137 months of follow-up (median = eight months, IQR = 2–18) (Table 1). The population was predominately male (61%), and 8% identified as MSM. In the previous year, 42% and 23% of the cohort were prescribed medication to treat a mental health issue or took an opioid for the treatment
Discussion
We used an observational study of OAT retention among HIV/HCV co-infected PWID to identify when OAT adherence sufficiently improved to inform DAA initiation in OAT settings. Our analyses found that after controlling for patient demographics and health characteristics, individuals retained in OAT for three or more months had higher odds of completing another twelve weeks of OAT; individuals retained in OAT for two or more months had improved odds of completing another eight weeks of OAT; and for
Acknowledgements
This work was supported by the National Institutes of Health (NIH) and National Institute for Drug Abuse (R01-DA041747); the BC Ministry of Health-funded “Seek and treat for optimal prevention of HIV & AIDS” pilot project; and JSG Montaner has received limited unrestricted funding, paid to his institution, from Abbvie, Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck, and ViiV Healthcare.
Conflict of interest
All authors report no potential conflict of interest. Preliminary results of the
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2020, International Journal of Drug PolicyCitation Excerpt :These ongoing barriers include, for instance, disinclination to seek treatment due to being asymptomatic of HCV, concerns about having to undergo phlebotomy (e.g., due to poor vein health), hesitancy related to treatment side effects, and the prioritization of other health and social concerns over one's HCV status (Harris et al., 2018; Litwin et al., 2019; Madden, Hopwood, Neale, & Treloar, 2018; Marshall et al., 2020). It is also well documented that healthcare providers have historically been overly paternalistic in their approach to providing HCV treatment to PWID, with previous research across Interferon- and DAA-based HCV treatment eras indicating that care providers have raised concerns about: capacity for optimal adherence among PWID (Grebely et al., 2017; Krook, Stokka, Heger, & Nygaard, 2007); the potential for HCV re-infection in the context of costly treatment regimens (Asher et al., 2016; Grebely et al., 2017; Lazarus et al., 2017); a presumed lack of motivation or capacity among PWID living with HCV (Litwin et al., 2019; Treloar, Newland, Rance, & Hopwood, 2010); and the negative impact of co-morbid human immunodeficiency virus (HIV) co-infection (Panagiotoglou et al., 2017; Scott et al., 2009), and past, current, or anticipated substance use (Boerekamps et al., 2018; Litwin et al., 2019). Despite these concerns, a growing body of clinical and behavioural evidence indicates that PWID are able to be successfully cured of HCV with DAAs at rates comparable to other populations (Asher et al., 2016; Chan, Young, Cox, Nitulescu, & Klein, 2018; Harris, 2017).
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