Delivering direct acting antiviral therapy for hepatitis C to highly marginalised and current drug injecting populations in a targeted primary health care setting

Background HCV prevalence estimates among people who inject drugs (PWID) in Ukraine is high (60%-90%), yet barriers to HCV treatment and care remain substantial including limited access to direct acting antiviral (DAA) medications. A feasibility scale-up project implemented HCV treatment in community-based settings to improve access to DAA treatment for key populations in this context. Methods Using program-level data and verified medical records, we describe the development, implementation processes and outcomes for HCV treatment for PWID and other risks groups. Most participants (76%) received a combination of sofosbuvir, pegylated interferon, and ribavirin for 12 weeks. Treatment enrollment started in June 2015; the first two waves are reported. Data on demographics, HIV characteristics, HCV genotype and RNA levels, including sustained virologic response (SVR) were obtained from verified medical records. We used logistic regression to examine the independent correlates of achieving a SVR. Results The project was implemented in 19 healthcare institutions from 16 regions of Ukraine, mainly within AIDS specialty centers. Our analytical sample included 1,126 participants who were mostly men (73%) and the majority were HIV co-infected (79%). Treatment retention was 97.7% and the proportion of participants who achieved SVR for the 1,029 (91%) with complete data was 94.3% (95% CI 92.8%–95.7%). PWID who were currently injecting had comparable SVR rates (89.2%, 95% CI 81.5–94.5%) to PWID not injecting (94.4%, 95% CI 92.4–96.1), PWID on methadone (94.4%, 95%CI 92.4–96.1), and ‘other’ risk group (95.2%, 95% CI 91.3–97.7). Independent factors associated with achieving a SVR were females sex (AOR: 3.44, 95% CI 1.45–8.14), HCV genotype 3 (AOR: 4.57, 95% CI 1.97 - 10.59) compared to genotype 1. SVR rates in PWID actively injecting did not differ significantly from any other group. Conclusion Both patient-level and structural factors influence HCV treatment scale-up in Ukraine, but patient-level outcomes confirm high levels of achieving SVR in PWID, irrespective of injection and treatment status.

Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 53%

Implementing and scaling up HCV treatment services for people who inject drugs and other high risk groups in Ukraine: An evaluation of programmatic and treatment outcomes

Mazhnaya

Meteliuk

Barnard

et al. 2017

“…Combined with data presented in a recent publication of this Journal , the evidence base that PWUDs can be treated successfully and achieve SVR in real-world settings is mounting. In all studies, drug use was not related to adherence, attendance for SVR testing, or SVR itself (Mason et al, 2017; Morris et al, 2017; Read et al, 2017). …”

Section: Discussionmentioning

confidence: 98%

High HCV cure rates for people who use drugs treated with direct acting antiviral therapy at an urban primary care clinic

Norton

Fleming

Bachhuber

et al. 2017

114

Background Though direct acting antivirals (DAAs) promise high cure rates, many providers and payers remain concerned about successful treatment for people who use drugs (PWUD), even among those engaged in opioid agonist treatment (OAT). The efficacy of DAAs among PWUD in real-world settings is unclear. Methods We conducted a cohort study of patients initiating HCV treatment between January 2014 and August 2015 (n = 89) at a primary care clinic in the Bronx, NY. Onsite HCV treatment with DAAs was performed by an HCV specialist, with support from a care coordinator funded by the NYC Department of Health. We identified four categories of drug use and drug treatment: (1) no active drug use/not receiving OAT (defined as non-PWUD); (2) no active drug use/receiving OAT; (3) active drug use/not receiving OAT; and (4) active drug use/receiving OAT. The primary outcome was SVR at 12 weeks post-treatment. Results Overall SVR rates were 95% (n = 41/43) for non-PWUD and 96% (n = 44/46) for patients actively using drugs and/or receiving OAT [p = 0.95]. There were no differences in SVR rates by drug use or drug treatment category. Compared to non-PWUD, those with no active drug use/receiving OAT had 100% SVR (n = 15/15; p = 1.0), those actively using drugs/not receiving OAT had 90% SVR (n = 9/10; p = 0.47), and those actively using drugs/receiving OAT had 95% SVR (20/21; p = 1.0). Conclusion Regardless of active drug use or OAT, patients who received DAA therapy at an urban primary care clinic achieved high HCV cure rates. We found no clinical evidence to justify restricting access to HCV treatment for patients actively using drugs and/or receiving OAT.

“…OAT retention is a strong predictor of long-term ART adherence among PWID (Roux et al, 2009), is associated with HCV treatment initiation (Midgard, Bramness, Skurtveit, Haukeland, & Dalgard, 2016), and has been found to improve adherence in studies conducted during the pegylatedinterferon era (Dimova, Zeremski, Jacobson, Hagan, & Des Jarlais, 2013). However, studies of people on OAT and recent injectors have found both populations able to complete a twelve week DAA treatment regimen irrespective of ongoing injecting drug use or OAT (Mason et al, 2017; Morris et al, 2017; Read et al, 2017), and studies which randomized people to immediate or delayed DAA treatment within OAT settings have observed loss to follow-up in the delayed treatment arms (Dore et al, 2016; Hilsden, Macphail, Grebely, Conway, & Lee, 2013). This suggests that ongoing injecting drug use is not associated with reduced response, prolonged delay in DAA initiation within OAT settings should be avoided, and although DAA retention and SVR are achievable outside OAT settings (Mason et al, 2017; Read et al, 2017), OAT remains an important setting for engaging PWID in HCV care and treatment.…”

Section: Discussionmentioning

confidence: 99%

“…However, studies of people on OAT and recent injectors have found both populations able to complete a twelve week DAA treatment regimen irrespective of ongoing injecting drug use or OAT (Mason et al, 2017; Morris et al, 2017; Read et al, 2017), and studies which randomized people to immediate or delayed DAA treatment within OAT settings have observed loss to follow-up in the delayed treatment arms (Dore et al, 2016; Hilsden, Macphail, Grebely, Conway, & Lee, 2013). This suggests that ongoing injecting drug use is not associated with reduced response, prolonged delay in DAA initiation within OAT settings should be avoided, and although DAA retention and SVR are achievable outside OAT settings (Mason et al, 2017; Read et al, 2017), OAT remains an important setting for engaging PWID in HCV care and treatment. Given the cost of DAA, and concerns regarding treatment adherence and subsequent antiviral resistance, our study provides indirect evidence in support of further implementation science research for DAA treatment initiation time among PWID on OAT without incurring the costs of treatment or drop out.…”

Section: Discussionmentioning

confidence: 99%

Initiating HCV treatment with direct acting agents in opioid agonist treatment: When to start for people co-infected with HIV?

Panagiotoglou

Krebs

Min

et al. 2017

Background Direct acting antivirals (DAA) raise the possibility of eliminating Hepatitis C virus (HCV) among people who inject drugs (PWID). However, concerns regarding treatment retention and reinfection challenge implementation efforts. Opioid agonist treatment (OAT) provides an opportunity to engage HCV-positive PWID into DAA-based treatment. Our objective was 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 the DAA treatment course. Methods This was a retrospective cohort study of HCV/HIV co-infected PWID from a population-level linked administrative database of people diagnosed and living with HIV in British Columbia, Canada between 01/1996 and 12/2013. We used monthly follow-up data after initial OAT entry and considered the effects of demographics, disease severity, and HIV and OAT treatment characteristics over time on the probability of subsequent OAT retention of ≥12 weeks, and ≥8 weeks for sensitivity analysis. We fit a generalized linear mixed model to the overall study population, and on stratified samples of those continuously engaged on combination antiretroviral therapy (≥95% ART adherence). A set of monthly indicator variables (months 1, …, 7, >7) were included to fulfil the study objective. Results Our study included 1427 HCV/HIV co-infected PWID (39.0% female, 68.8% OAT-naive). The odds of subsequent twelve-week retention in OAT were statistically significantly greater in month 3 versus month 1 (adjusted odds ratio: 1.18; 95% confidence interval: 1.02, 1.37); and the odds of subsequent 8- week retention in OAT were statistically significantly greater in month 2 versus month 1 (1.15, 95% CI: 1.02, 1.31). Among continuously ART-adherent individuals, the odds of subsequent twelve-week retention were not statistically significantly greater than in month 1 (month 2: 1.12 (0.82,1.51); month 3: 1.08 (0.79, 1.47); month 4: 1.24 (0.91, 1.71)). Conclusion We provide evidence that among HCV/HIV co-infected PWID, those retained in OAT for three or more months had higher odds of completing an additional twelve weeks of OAT, compared to no difference in those already receiving ART. These data may have implications for adherence to DAA therapy and further studies are needed to understand the optimal timing of DAA therapy in PWID receiving and not receiving OAT.