Impact of Recent Drug Use on the Efficacy of Elbasvir/Grazoprevir for HCV-infected People on Opioid Agonist Therapy

Juan Macías; Francisco Téllez; Ignacio de los Santos; Luis E. Morano; Dolores Merino; Rafael Granados; Francisco Vera-Mendez; Alejandro González-Serna; Esther Campo-Moneo; Lucio García-Fraile; Federico García; Luis M. Real; Juan A. Pineda

Disclosures

J Viral Hepat. 2021;28(6):878-886. 

In This Article

Abstract and Introduction

Abstract

Elbasvir/grazoprevir (EBR/GZR) use in drug users on opiate agonist therapy (OAT) is supported by the C-EDGE Co-STAR trial. SVR rates in this study were within those found in the rest of patients included by the EBR/GZR development programme. In clinical practice, however, efficacy could theoretically be lower. Thus, we aimed at evaluating the SVR rates of EBR/GZR among people who injected drugs (PWID) with and without OAT in clinical practice. Patients starting EBR/GZR included in the HEPAVIR-DAA (NCT02057003), recruiting HIV/HCV-coinfected patients or the GEHEP-MONO (NCT02333292), including HCV-monoinfected individuals, prospective cohorts were analysed. Overall SVR12 (ITT), discontinuations due to adverse effects and drop-outs were evaluated. The same analysis was carried out for PWID with and without OAT. 336 patients had started EBR/GZR and reached the SVR12 evaluation date. 318 [95%, 95% confidence interval (95% CI): 92%-98%] patients achieved SVR12. SVR12 was 97% (95% CI: 93%-99%, n/N = 141/145) among people who never used injecting drugs, 94% (95% CI: 88%-97%, n/N = 117/125) among PWIDs without OAT and 91% (95% CI: 81%-97%, n/N = 60/66) among PWIDs with OAT (p = 0.134). Five (1.5%) patients showed relapses, and two (0.6%) individuals showed viral breakthrough. The SVR12 rate for recent drug users was 69% (n/N = 18/26) compared with 97% (n/N = 276/284) for individuals without recent drug use (in the prior year) (p < 0.001). Among recent drug users, three (12%) showed relapses, and five (19%) were lost-to-follow-up. The SVR rates achieved with EBR/GZR were high in real-world conditions of use. However, PWID with recent drug use reach suboptimal response rates with EBR/GZR.

Introduction

The prevalence of hepatitis C virus (HCV) infection is far higher among people who inject drugs (PWID) currently or previously than in the general population.[1,2] The World Health Assembly adopted elimination of viral hepatitis as a public health threat by 2030.[3] To achieve that ambitious target, sufficient coverage for five core interventions should be reached. One of those interventions was HCV treatment and cure. Highly effective and safe direct-acting antiviral (DAA) combinations make HCV infection a curable disease in nearly all patients. However, uptake of treatment among PWID is still low.[4]

Elbasvir/Grazoprevir (EBR/GZR) has demonstrated high efficacy and tolerability in a variety of settings.[5–7] In the setting of drug use, EBR/GZR is supported by a specific double-blind randomized clinical trial dedicated to drug users on opiate agonist therapy (OAT), the C-EDGE Co-STAR trial.[8] The rates of SVR were within those found in the rest of the EBR/GZR development programme.[5–7] Also, tolerability and adverse effects of EBR/GZR were similar to placebo in this study.[8] Adherence to therapy was good, and the frequency of drop-outs was low. Reinfections after sustained virological response (SVR) were not more frequent than in other phase 3 clinical trials with different DAAs.[8]

In clinical practice, lower SVR rates than in clinical trials could be achieved, essentially due to a higher likelihood of losses to follow-up and a lower adherence, since adherence treatment and medical appointments are by far more strictly controlled in the setting of trials. Before EBR/GZR was widely available in Spain, we found that HCV-infected PWID on OAT had the lowest SVR rate to DAA combinations in clinical practice.[9] This was mainly attributable to higher rates of discontinuations due to adverse events and, especially, of losses to follow-up.[9] Active drug use was more frequent among PWID on OAT.[9] Accounting for active drug use nearly closed the gap in SVR rates among PWID, with and without OAT, and patients who never used drugs.[9] It is not known whether the high efficacy of EBR/GZR among drug users on OAT the setting of a clinical trial may be replicated in clinical practice. Because of this, we compared the rates of SVR to EBR/GZR among PWID, with and without OAT, in daily practice.

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