Abstract and Introduction
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.
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. 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.
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. 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. 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.
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. This was mainly attributable to higher rates of discontinuations due to adverse events and, especially, of losses to follow-up. Active drug use was more frequent among PWID on OAT. Accounting for active drug use nearly closed the gap in SVR rates among PWID, with and without OAT, and patients who never used drugs. 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.
J Viral Hepat. 2021;28(6):878-886. © 2021 Blackwell Publishing