Treatment adherence and support for people who inject drugs taking direct-acting antiviral therapy for hepatitis C infection.

A community-based public health facility in Sydney, Australia, the Kirketon Road Centre (KRC), provides health care to people who inject drugs (PWID), homeless and other marginalized people. Since March 2016, KRC has provided treatment for chronic hepatitis C virus (HCV) with direct-acting antivirals (DAAs). We aimed to evaluate treatment adherence amongst clients taking DAAs in a highly marginalized population. All clients who commenced DAA therapy prior to March 2018 at KRC were included in this observational cohort with a subset of clients attending daily or weekly for enhanced adherence support and dosing. Demographic, behavioural, clinical measures and medication dosing were recorded, and adherence was calculated as the proportion of doses taken during the expected treatment duration. Factors associated with adherence were examined using logistic regression. A total of 242 individuals commenced DAA therapy, of whom 79 (32%) received enhanced adherence support. Enhanced support was associated with homelessness, daily injecting, Aboriginality, mental health co-morbidity and poly-drug use (all P < .001). Overall adherence was 86%, and 92% of patients missed one or more doses (median 10, IQR 4-24). At least 90% adherence during planned duration was seen in 38%, but increased to 66% by continuing therapy beyond planned duration. Intention-to-treat SVR12 was 68% and 66% in the enhanced adherence support sub-population, with 29% lost to follow-up by SVR12 testing. There were only 2 (0.8%) documented virological failures. Per-protocol SVR12 was 99% and 96% in the enhanced adherence support sub-population. In conclusion, adherence support may benefit those with multiple markers of marginalization. Extension of therapy beyond planned duration is a pragmatic strategy to enhance completion. Strategies to improve follow-up, particularly post-treatment are required.

Hepatitis C (HCV) Reinfection and Risk Factors among Clients of a Low-Threshold Primary Healthcare Service for People Who Inject Drugs in Sydney, Australia.

Hepatitis C (HCV) reinfection studies have not focused on primary healthcare services in Australia, where priority populations including people who inject drugs (PWID) typically engage in healthcare. We aimed to describe the incidence of HCV reinfection and associated risk factors in a cohort of people most at risk of reinfection in a real-world community setting. We conducted a secondary analysis of routinely collected HCV testing and treatment data from treatment episodes initiated with direct-acting antiviral (DAA) therapy between October 2015 and June 2021. The overall proportion of clients (N = 413) reinfected was 9% (N = 37), and the overall incidence rate of HCV reinfection was 9.5/100PY (95% CI: 6.3-14.3). Reinfection incidence rates varied by sub-group and were highest for Aboriginal and/or Torres Strait Islander people (20.4/100PY; 95% CI: 12.1-34.4). Among PWID (N= 321), only Aboriginality was significantly associated with reinfection (AOR: 2.73, 95% CI: 1.33-5.60, p = 0.006). High rates of HCV reinfection in populations with multiple vulnerabilities and continued drug use, especially among Aboriginal and Torres Strait Islander people, highlight the need for ongoing regular HCV testing and retreatment in order to achieve HCV elimination. A priority is resourcing testing and treatment for Aboriginal and/or Torres Strait Islander people. Our findings support the need for novel and holistic healthcare strategies for PWID and the upscaling of Indigenous cultural approaches and interventions.

Single-visit hepatitis C point-of-care testing, linkage to nursing care, and peer-supported treatment among people with recent injecting drug use at a peer-led needle and syringe program: The TEMPO Pilot Study.

BACKGROUND: Point-of-care hepatitis C virus (HCV) RNA testing can facilitate single-visit diagnosis and treatment. This study evaluated a single-visit test and treat intervention integrating point-of-care HCV RNA testing, linkage to nursing care, and peer-supported engagement/delivery of treatment among people with recent injecting drug use at a peer-led needle and syringe program (NSP). METHODS: TEMPO Pilot is an interventional cohort study of people with recent injecting drug use (previous month) recruited between September 2019-February 2021 from one peer-led NSP in Sydney, Australia. Participants received point-of-care HCV RNA testing (Xpert HCV Viral Load Fingerstick), linkage to nursing care, and peer-supported engagement/delivery of treatment. The primary endpoint was the proportion initiating HCV therapy. RESULTS: Among 101 people with recent injecting drug use (median age 43; 31% female), 27% (n = 27) were HCV RNA detectable. Treatment uptake was 74% (20 of 27; sofosbuvir/velpatasvir, n = 8; glecaprevir/pibrentasvir, n = 12). Among people initiating treatment (n = 20), 45% (n = 9) initiated treatment at the same visit, 50% (n = 10) in the next 1-2 days, and 5% on day 7 (n = 1). Two participants initiated treatment outside the study (overall treatment uptake 81%). Reasons for not initiating treatment included loss to follow-up (n = 2), no reimbursement (n = 1), not suitable for treatment (mental health) (n = 1), and inability to perform liver disease assessment (n = 1). In the full analysis set, 60% (12 of 20) completed treatment and 40% (8 of 20) had a sustained virological response (SVR). In the evaluable population (excluding people without an SVR test), SVR was 89% (8 of 9). CONCLUSION: Point-of-care HCV RNA testing, linkage to nursing, and peer-supported engagement/delivery led to high HCV treatment uptake (majority single-visit) among people with recent injecting drug use attending a peer-led NSP. The lower proportion of people with SVR highlights the need for further interventions to support treatment completion.

The Overdose Response with Take Home Naloxone (ORTHN) project: Evaluation of health worker training, attitudes and perceptions.

INTRODUCTION: Naloxone is a life-saving medication that reverses opioid overdose; naloxone can be provided on a 'take-home' basis so naloxone can be administered outside of the health-care setting. The Overdose Response and Take Home Naloxone (ORTHN) project established a model of care for take-home naloxone (THN) interventions across alcohol and other drug and harm reduction services in NSW, Australia. This paper evaluates the staff training and credentialing program, and examines staff attitudes and perspectives regarding the provision of THN interventions in these settings. METHODS: Staff across seven services were trained through a 'train-the-trainer' credentialing model to deliver ORTHN, including naloxone supply. Staff were surveyed regarding their experience, attitudes and knowledge on THN prior to and after training, and after 6 months. At the 6 months follow up, staff were asked about the interventions they provided, barriers and enablers to uptake, and opinions regarding future rollout. RESULTS: A total of 204 staff were trained and credentialed to provide the ORTHN intervention. Most (60%) were nurses, followed by needle syringe program workers and allied health/counsellors (32%). Linear and logistic regression analyses indicated that the training program was associated with significant improvements in staff knowledge and attitudes towards overdose and THN; however, only attitudinal improvements were maintained over time. There were high rates of staff satisfaction with the ORTHN intervention and training. DISCUSSION/CONCLUSIONS: The ORTHN program is 'fit for purpose' for broad implementation in these settings. A number of potential barriers (e.g. time, medication and staffing costs) and enablers (e.g. peer engagement, regulatory framework for naloxone supply) in implementing THN interventions were identified.

Awareness of HCV Status and Preferences for Testing and Treatment among People with Recent Injecting Drug Use at a Peer-Led Needle and Syringe Program: The TEMPO Pilot Study.

BACKGROUND: New technologies and therapies allow the possibility of a single-visit test and treat model for hepatitis C virus (HCV), addressing some of the barriers to care faced by people who inject drugs. METHODS: The TEMPO Pilot Study was an interventional cohort study evaluating a single-visit test and treat intervention among people with recent injecting drug use at a one peer-led needle and syringe program (NSP) in Sydney, Australia between September 2019 and February 2021. This analysis evaluated awareness of HCV status and agreement of self-report with HCV RNA test results. The analysis also assessed acceptability of: modality of result delivery, modality of blood sampling, site of treatment, and duration of treatment. RESULTS: Among 101 participants (median age 43; 31% female), 100 had a valid HCV RNA test result and 27% (27/100) were HCV RNA detectable. Overall, 65% (65/100) were aware of their status. Among people with a positive HCV RNA result, 48% (13/27) were aware of their status. People preferred same-day HCV test results (95%, 96/101), and preferred to receive results in person (69%, 70/101). Receiving treatment at an NSP was acceptable (100%, 101/101) and 78% (79/101) were willing to discuss their health with a peer NSP worker. CONCLUSION: Half of people with current HCV infection were aware of their status. The high acceptability of simplified testing and treatment pathways delivered at NSPs indicates that this is an appropriate strategy to improve HCV awareness and treatment uptake in this population.

Elbasvir and grazoprevir for hepatitis C virus genotype 1 infection in people with recent injecting drug use (DARLO-C): An open-label, single-arm, phase 4, multicentre trial.

BACKGROUND AND AIMS: Direct-acting antiviral therapy for hepatitis C virus (HCV) is effective, but few prospective studies among people with ongoing injecting drug use exist. This study evaluated the efficacy of elbasvir/grazoprevir in people with HCV genotype 1/4 (G1/4) infection and recent injecting drug use. An exploratory aim evaluated the feasibility of fingerstick point-of-care HCV RNA testing prior to and following treatment. METHODS: DARLO-C (http://clinicaltrials.gov: NCT02940691) is an open-label phase 4 trial. Participants were recruited between May 2017 and March 2018 from two drug treatment clinics, two hospital clinics, and one community clinic in Australia. Inclusion criteria included recent injection drug use (previous 6 months) and HCV G1/4 infection. Exclusion criteria included prior HCV treatment and decompensated liver disease. Participants received elbasvir/grazoprevir once-daily for 12 weeks. The primary endpoint was undetectable HCV RNA 12 weeks post-treatment (SVR). Fingerstick whole-blood samples were tested using the Xpert HCV Viral Load Fingerstick (Xpert HCV VL Fingerstick) assay and compared to the Aptima HCV Quant Dx Assay on plasma samples. RESULTS: Of a planned 150 participants, 32 were enrolled due to slower than anticipated recruitment [median age 46 years, 10 (31%) female, 29 (91%) G1a]. Eighteen (56%) were receiving opioid agonist therapy and 29 (91%) injected in the previous month. Twenty-six (81%) of 32 completed treatment (lost to follow-up, n = 5; incarceration, n = 1). There were no virological failures. Twenty-four (75%, 95% CI 59%-91%) of 32 achieved SVR. Two participants who completed treatment did not have SVR (loss to follow-up, n = 1; refused test, n = 1). Among paired samples (n = 36), sensitivity of the Xpert HCV VL Fingerstick assay for HCV RNA detection was 100.0% (95% CI 75.3%-100.0%) and specificity was 95.7% (95% CI 78.1%-99.9%). CONCLUSION: Elbasvir/grazoprevir is effective among people with HCV G1 with recent injecting drug use. Implementation of point-of-care HCV RNA testing was feasible, but the high error rate requires investigation.

Designing, implementing and evaluating the overdose response with take-home naloxone model of care: An evaluation of client outcomes and perspectives.

INTRODUCTION AND DESIGNS: Take-home naloxone (THN) interventions are an effective response to preventing overdose deaths, however uptake across Australia remains limited. This project designed, implemented and evaluated a model of care targeting opioid users attending alcohol and other drug (AOD) treatment, needle and syringe programs (NSP) and related health services targeting people who inject drugs. DESIGN AND METHODS: Service providers, consumers and regulators collaboratively designed a THN brief intervention (ORTHN, Overdose Response with Take-Home Naloxone) involving client education and supply of naloxone in pre-filled syringes, delivered by nursing, allied health and NSP workers. ORTHN interventions were implemented in over 15 services across New South Wales, Australia. The evaluation included client knowledge, attitudes, substance use and overdose experiences immediately before and 3 months after ORTHN intervention in a subsample of participants. RESULTS: Six hundred and sixteen interventions were delivered, with 145 participants recruited to the research subsample, of whom 95 completed the three-month follow up. Overdose-related attitudes amongst participants improved following ORTHN, with no evidence of increased substance use or failure to implement other 'first responses' (e.g. calling an ambulance). Nine participants (10%) reversed an overdose using THN in the follow-up period. Participants identified a willingness to access THN from a range of services. While a minority (16%) indicated they were unwilling to pay for THN, the median price that participants were willing to pay was $AUD20 (IQR $10.40). DISCUSSION AND CONCLUSIONS: The ORTHN model of care for THN appears an effective way to disseminate THN to people who use opioids attending AOD, NSP and related health-care settings.

Feasibility and acceptability of adherence support for direct acting antiviral therapy for hepatitis C in a low-threshold primary health-care opioid agonist treatment program.

INTRODUCTION AND AIMS: To maximise the benefits of direct acting antivirals in Australia, innovative options for marginalised populations to receive daily or weekly medication may be beneficial. This study evaluated the feasibility and acceptability of direct acting antivirals provision by leveraging an opioid agonist treatment program to support adherence regardless of opioid agonist treatment enrolment. DESIGN AND METHODS: Feasibility was evaluated by monitoring selection of dosing options by clients initiating direct acting antivirals during the first 6 months. Client acceptability was assessed using a cross-sectional survey after 6 months. Pre- and post-implementation surveys of attitudes and concerns regarding the program were compared to evaluate staff acceptability. RESULTS: Among 79 clients commencing direct acting antivirals, 30 (38%) chose adherence support. Among these, 12 (40%) were not simultaneously enrolled in opioid agonist treatment. Clients were satisfied with service provision and access despite introducing daily dosing. All highly marginalised clients receiving direct acting antivirals with adherence support found this helpful. Staff concerns identified prior to the program proved unfounded. DISCUSSION AND CONCLUSIONS: This study demonstrates providing adherence support for direct acting antivirals regardless of client participation in opioid agonist treatment is both feasible and acceptable with minimal impact on service provision. Availability of direct acting antivirals in opioid agonist treatment or primary health-care settings expands the pool of people who may receive effective treatment for hepatitis C virus and reduces treatment barriers.

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

BACKGROUND: The Kirketon Road Centre (KRC) is a community-based public health facility in Sydney, Australia, that provides healthcare to people who inject drugs (PWID), including hepatitis C virus (HCV) treatment. From March 2016, the Australian Government has provided access to direct-acting antivirals (DAA) for adults with chronic HCV, without liver disease stage or drug and alcohol use restrictions. The aim of this study was to report DAA treatment outcomes among highly marginalised PWID treated at KRC. METHODS: All individuals initiating DAA treatment at KRC and due for sustained virological response (SVR12) testing by end 2016 were included. Demographic, drug use behaviour, clinical parameters, adherence support and HCV treatment outcomes, including SVR12 were recorded. Factors associated with SVR12, loss-to-follow-up (LTFU) and delayed SVR12 testing (>SVR16) were assessed by multivariate analysis. SVR12 was assessed by intention-to-treat (ITT) and modified ITT, the latter excluding individuals with an end-of-treatment response (ETR) but no SVR12 assessment, or who postponed their SVR12 date due to treatment interruption. RESULTS: A total of 72 individuals commencing DAAs were included, of whom 67% were male, 30% homeless, and 32% Aboriginal. All had a lifetime history of injecting drug use, with 75% having injected within the last six months, and 44% injecting at least weekly; 25% were also enrolled in opioid substitution therapy. Twenty-five (35%) individuals elected to receive an enhanced adherence-support package. Fifty-nine of 72 (82%) individuals due for SVR12 attended for testing, of whom 59/59 (100%) achieved SVR, providing an ITT SVR of 82%. A further six individuals had undetectable HCV RNA at ETR, but no SVR12 assessment, and one interrupted treatment, providing a mITT SVR of 91%. Homelessness was associated with delayed SVR12 testing (OR 24.9 95%CI 2.9-212.8, p=0.003). There was no association between LTFU and frequency of drug injection, last drug injected, or planned treatment duration. CONCLUSION: This study confirms that PWID can be successfully treated for HCV in a real-world setting using an integrated primary health care model. It also demonstrates feasibility to upscale DAA therapy in high-risk PWID populations, with potential individual and population-level public health benefits. Enhanced efforts are required to optimise post-treatment follow-up.