Loss to Follow-up: A Significant Barrier in the Treatment Cascade With Direct-acting Therapies

Maryam Darvishian; Stanley Wong; Mawuena Binka; Amanda Yu; Alnoor Ramji; Eric M. Yoshida; Jason Wong; Carmine Rossi; Zahid A. Butt; Sofia Bartlett; Margo E. Pearce; Hasina Samji; Darrel Cook; Maria Alvarez; Mei Chong; Mark Tyndall; Mel Krajden; Naveed Z. Janjua

Disclosures

J Viral Hepat. 2020;27(3):243-260. 

In This Article

Abstract and Introduction

Abstract

Effectiveness of direct-acting antiviral (DAA) therapies could be influenced by patient characteristics such as comorbid conditions, which could lead to premature treatment discontinuation and/or irregular medical follow-ups. Here, we evaluate loss to follow-up and treatment effectiveness of sofosbuvir/ledipasvir ± ribavirin (SOF/LDV ± RBV), ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (OBV/PTV/r + DSV ± RBV) for hepatitis C virus (HCV) genotype 1 (GT1) and sofosbuvir + ribavirin (SOF + RBV) for genotype 3 (GT3) in British Columbia Canada: The British Columbia Hepatitis Testers Cohort includes data on individuals tested for HCV since 1992, integrated with medical visit, hospitalization and prescription drug data. HCV-positive individuals who initiated DAA regimens, irrespective of treatment completion, for GT1 and GT3 until 31 December, 2017 were included. Factors associated with sustained virological response (SVR) and loss to follow-up were assessed by using multivariable logistic regression models. In total 4477 individuals initiated DAAs. The most common prescribed DAA was SOF/LDV ± RBV with SVR of 95%. The highest SVR of 99.5% was observed among OBV/PTV/r + DSV-treated patients. Overall, 453 (10.1%) individuals were lost to follow-up. Higher loss to follow-up was observed among GT1 patients treated with OBV (17.8%) and GT3 patients (15.7%). The loss to follow-up rate was significantly higher among individuals aged <60 years, those with a history of injection drug use (IDU), on opioid substitution therapy and with cirrhosis. Our findings indicate that loss to follow-up exceeds viral failure in HCV DAA therapy and its rate varies significantly by genotype and treatment regimen. Depending on the aetiology of lost to follow-up, personalized case management for those with medical complications and supporting services among IDU are needed to achieve the full benefits of effective treatments.

Introduction

About 71 million people are living with chronic hepatitis C (HCV) infection worldwide.[1] Individuals with chronic infection are at high risk of liver-related morbidity (eg cirrhosis and hepatocellular carcinoma) and mortality.[1,2] In Canada, between 230 000 and 450 000 individuals are infected with HCV, mainly genotypes 1 (GT1; 65%) and 3 (GT3; 20%).[3–5]

The development of direct-acting antiviral (DAA) therapies was a major breakthrough in the history of HCV treatment. Introduction of sofosbuvir-based regimens, including sofosbuvir + ribavirin (SOF + RBV, approved December 2013) and sofosbuvir/ledipasvir (SOF/LDV; approved October 2014) combination therapy against HCV GT1 and GT3, resulted in high sustained virological response (SVR).[6,7] Similarly, subsequently approved regimens such as ombitasvir/paritaprevir/ritonavir/dasabuvir ± ribavirin (OBV/PTV/r + DSV; approved March 2015) against HCV GT1 showed SVR rates above 95%.[8]

Both clinical trials and observational studies reported high efficacy and effectiveness for DAA regimens against GT1 and GT3.[6,7,9–11] Treatment access in British Columbia (BC) and the rest of Canada for the first few years was restricted to people with advanced stage liver disease (fibrosis level ≥ F2). In March 2018, by removal of fibrosis restriction eligibility, DAA access expanded to all HCV-infected individuals including people who inject drugs (PWID). Historically, PWID were less likely to be treated because of fear of noncompliance with poorly tolerated, long interferon-based treatments.[12] Although DAAs have removed barriers related to longer treatment duration and poor tolerability, data from real-world settings on loss to follow-up (LTF) and premature discontinuation of DAA therapies are very limited. While newer DAAs are highly efficacious, LTF could blunt the overall real-world effectiveness.[13,14] Thus, characterizing LTF and its predictors is important towards achieving World Health Organization (WHO) elimination goals.[15]

In this study, we sought to determine SVR among all people who initiated DAA therapy, regardless of treatment completion. We also assessed LTF and its contributing factors among a diverse real-world HCV-infected population. Specifically, in this study we aimed to provide detailed information for clinicians about the HCV-infected individuals who might be at a higher risk of LTF and treatment failure after treatment initiation.

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