Randomized Clinical Trial

Direct-acting Antivirals as Treatment for Hepatitis C in People Who Inject Drugs

Delivered in Needle and Syringe Programs Via Directly Observed Therapy Versus Fortnightly Collection

Lewis Beer; Sarah Inglis; Amy Malaguti; Christopher Byrne; Christian Sharkey; Emma Robinson; Kirsty Gillings; Andrew Radley; Adrian Hapca; Brian Stephens; John Dillon

Disclosures

J Viral Hepat. 2022;29(8):646-653. 

In This Article

Abstract and Introduction

Abstract

Hepatitis C virus (HCV) treatment in people who inject drugs (PWID) is delivered within settings frequented by PWID, such as needle and syringe programs (NSP). The optimal direct-acting antiviral (DAA) dispensing regimen among NSP clients is unknown. This study compared cures (Sustained virologic response 12 weeks post-treatment, [SVR12]) across three dispensing schedules to establish non-inferiority of fortnightly dispensing versus directly observed therapy. The ADVANCE HCV study was a randomized, unblinded trial, recruiting PWID attending NSP in Tayside, Scotland, between January 2018 and November 2019. HCV-positive participants were randomized to receive DAAs via directly observed therapy, fortnightly provision or fortnightly provision with psychological intervention. A modified intention to treat analysis was used to identify differences in cures between the three treatment regimes. The study was registered with clinicaltrials.gov; NCT03236506. A total of 110 participants completed the study. 33 participants received directly observed therapy, with 90.91% SVR12; 37 received fortnightly provision, with 86.49% SVR12 and 40 received fortnightly provision and psychological intervention at treatment initiation, with 92.50% SVR12. Analysis showed no significant difference in SVR12 (p = 0.67). This study did not demonstrate a statistically significant difference in cure rate between groups. This provides evidence of the non-inferiority of fortnightly dispensing of direct-acting antivirals (DAAs) compared to directly observed therapy among PWID. It suggests that tight control of adherence through directly observed therapy dispensing of DAAs among this population offers no therapeutic advantage. Therefore, less restrictive dispensing patterns can be used, tailored to patient convenience.

Introduction

Hepatitis C virus (HCV) is a blood-borne virus (BBV) spread mainly through blood-to-blood contact. An estimated 58 million people worldwide have chronic HCV infection, which can lead to cirrhosis and liver cancer.[1] In 2016, the World Health Organization (WHO) published targets to facilitate elimination of HCV as a public health threat by 2030, diagnosis of 90% of individuals with chronic HCV and treatment of 80% of those diagnosed.[2] Infection in higher-income countries is predominantly via injecting drug use (IDU); global estimates indicate 8.5% of people infected recently injected drugs.[3] Approximately 40% of people with recent injecting drug use are estimated to have HCV infection.[3] This indicates that people who inject drugs (PWID) are a key population for HCV treatment, to reduce both the disease burden and infection transmission. Providing treatment pathways to PWID is a critical component of HCV elimination.

Direct-acting antiviral (DAA) therapies are safe, efficacious and have shorter regimens than previous medications, increasing suitability for community settings.[4] Cure, defined as elimination of virus 12 weeks post-treatment (sustained virologic response, [SVR12]), was as high as 95% in clinical trials.[5] These trials previously excluded PWID; and data showing DAA efficacy in PWID, treated in community settings, were scarce.[6] This has since been improved, with trials taking place in community settings.[7,8] Treating PWID has proved challenging due to barriers deterring PWID from seeking treatment.[9,10] These include stigma against PWID in health settings, patients' infection risk perception and their attitudes towards illness severity and treatment.[11] The belief that PWID will demonstrate poor adherence to treatment and have poor success rates due to illicit drug or alcohol use has hindered treatment opportunities.[12] Many countries still restrict access to DAAs, in low- and middle-income countries due to cost and fear of export to high-income countries,[13] and in parts of Europe, access is still restricted based on fibrosis stage or drug/alcohol use.[14] This led to trials of DOT,[15] which may be acceptable for people on opiod agonist therapy (OAT) who are accustomed to daily collection, but can be disruptive to those with little experience of DOT and may be a barrier to treatment.

Over the past 6 years, treatment and care for people with HCV in NHS Tayside has been scaled up and novel treatment pathways established.[16] Together with conventional hospital-based HCV treatment, community-based treatment has been embedded via a combination of NHS and clinical trial-based delivery in sites including: addiction treatment centres/community clinics, pharmacies,[17–19] prisons and NSP.[20] Testing and treatment are led by specialist nurses with clinician oversight and pharmacist/psychologist participation.

The use of NSP as locations for treatment has grown globally, with studies in these settings also carried out in Georgia,[21] Australia[22–24] and the United States.[25]

The aim of this study[26] was to treat PWID with DAAs and determine whether provision of medication on a fortnightly basis is non-inferior to provision via DOT, often considered the ultimate adherence aid but also restrictive for the individual.[27,28]

processing....