Efficacy and Safety of Ledipasvir/Sofosbuvir With and Without Ribavirin in Patients With Chronic HCV Genotype 1 Infection Receiving Opioid Substitution Therapy: Analysis of Phase 3 ION Trials

Grebely, Jason; Mauss, Stefan; Brown, Ashley; Bronowicki, Jean–Pierre; Puoti, Massimo; Wyles, David L.; Natha, Macky; Zhu, Yu; Yang, Junming; Kreter, Bruce; Brainard, Diana M.; Yun, Chohee; Carr, Val; Dore, Gregory J.

doi:10.1093/cid/ciw580

Cited by 90 publications

(77 citation statements)

References 23 publications

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“…The comparable SVR12 outcomes in this post hoc analysis are consistent with previous data of interferon-based HCV therapy [7][8][9] and interferon-free DAA therapy for chronic HCV G1 among people receiving OST [10][11][12]. However, this study adds considerably to the literature, given that almost all studies of DAA therapy among people receiving OST are restricted to people with HCV G1, G4, or G6.…”

Section: Discussionsupporting

confidence: 89%

Efficacy and Safety of Sofosbuvir/Velpatasvir in Patients With Chronic Hepatitis C Virus Infection Receiving Opioid Substitution Therapy: Analysis of Phase 3 ASTRAL Trials

et al. 2016

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In this analysis of the ASTRAL trials (non-opioid substitution therapy [OST], n = 984; OST, n = 51) evaluating the once-daily, pan-genotypic regimen of sofosbuvir/velpatasvir for hepatitis C virus infection, OST did not impact completion, adherence, sustained virologic response (SVR12), or safety. SVR12 was 96% (95% confidence interval, 87%, >99%) in those receiving OST.Keywords. HCV; OST; PWID; sofosbuvir; velpatasvir.People who inject drugs (PWID) are disproportionately affected by hepatitis C virus (HCV) infection [1]. People with a history of injection drug use include those who have stopped injecting, those with recent injecting, and those receiving opioid substitution therapy (OST; eg, methadone or buprenorphine), some of whom may also have recently injected drugs. Data are lacking on HCV treatment outcomes with interferon-free direct-acting antiviral agents (DAAs) among people receiving OST, particularly people with genotypes (G) other than HCV G1. The phase 3 ASTRAL 1-3 trials evaluated the efficacy and safety of sofosbuvir/velpatasvir in patients with chronic HCV genotypes 1-6 [2, 3]. People receiving stable OST were eligible for inclusion, but people with clinically relevant illicit drug use within 12 months or a positive urine drug test at screening were excluded. No drug screens were performed during or following treatment. These clinical trial populations are highly selected, included people on stable OST, excluded people with recent drug use, and may not be representative of recent PWID populations. However, there are little data on interferon-free DAA therapy among people receiving OST.The aim of this post hoc analysis was to evaluate treatment completion, adherence, sustained virologic response (SVR), and safety of sofosbuvir/velpatasvir in people receiving OST without drug use at screening. METHODS Study Participants and DesignFrom 18 July 2014 to 19 December 2014 participants were enrolled in 3 international, multicenter, randomized open-label trials, including ASTRAL 1-3 (ClinicalTrials.gov: NCT02201940, NCT02220998, and NCT02201953) [2,3]. A fixed-dose combination tablet of sofosbuvir/velpatasvir 400 mg/100 mg was administered for 12 weeks in patients with chronic HCV genotypes 1-6. These studies have been described previously [2,3].Participants receiving OST were eligible for inclusion in the ASTRAL studies. Patients were excluded if they had clinically significant drug use within 12 months of screening (as assessed by the investigator) or a noncannabinoid detected by a positive urine drug test during the screening phase not explained by a prescription medication. No drug screens were performed during or following treatment. Study EndpointsIn this analysis, endpoints included treatment completion, adherence (≥90% of doses), SVR12, safety (adverse events [AEs] and serious AEs), and reinfection. The analysis population included all randomized patients who received at least 1 dose of sofosbuvir/velpatasvir. Adherence was calculated by dividing the number of total doses received during therapy...

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Section: Discussionsupporting

confidence: 89%

Efficacy and Safety of Sofosbuvir/Velpatasvir in Patients With Chronic Hepatitis C Virus Infection Receiving Opioid Substitution Therapy: Analysis of Phase 3 ASTRAL Trials

et al. 2016

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“…In another paper from the Feld, et al, 2014;J. Grebely, I. M. Jacobson, et al, 2017;Grebely, Mauss, et al, 2016;Puoti, et al, 2014;Zeuzem, et al, 2015). However, the majority of these trials excluded people with active drug use from participation.…”

Section: Hcv Treatment For Pwidmentioning

confidence: 99%

Elimination of hepatitis C virus infection among PWID: The beginning of a new era of interferon-free DAA therapy

Grebely

Bruneau

Bruggmann

et al. 2017

International Journal of Drug Policy

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“…Phase II and III trials of DAA therapy have demonstrated similar high efficacy among people receiving OST as compared with people not receiving OST [28][29][30][31]. However, in large part, these individuals have been stable on OST and people reporting recent drug use have been excluded, either by time since the last reported drug use or by urine drug screen.…”

Section: People Who Inject Drugsmentioning

confidence: 99%

HCV Cure and Reinfection Among People With HIV/HCV Coinfection and People Who Inject Drugs

Martinello¹,

Hajarizadeh²,

Grebely³

et al. 2017

Curr HIV/AIDS Rep

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Concern that HCV reinfection may compromise HCV treatment outcomes is sometimes cited as a reason for not offering treatment to current and former PWID. However, the incidence of reinfection following interferon-based treatment for chronic HCV is low among PWID. Reinfection rates in HIV-positive men-who-have-sex-with-men (MSM) are varied, with high incidence reported in some cohorts. Mathematical modelling suggests that substantial reductions in HCV incidence and prevalence could be achieved with targeted DAA therapy among those at the highest risk of ongoing transmission. This review will summarise the recent literature on DAA efficacy in PWID and people with HIV/HCV coinfection, discuss the individual- and population-level impact of DAA treatment scale-up and reinfection, and highlight ongoing and future research questions in expanding HCV care and treatment to those populations at high risk of ongoing HCV transmission.

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Efficacy and Safety of Ledipasvir/Sofosbuvir With and Without Ribavirin in Patients With Chronic HCV Genotype 1 Infection Receiving Opioid Substitution Therapy: Analysis of Phase 3 ION Trials

Abstract: ION-1 (NCT01701401); ION-2 (NCT01768286); and ION-3 (NCT01851330).

Cited by 90 publications

References 23 publications

Efficacy and Safety of Sofosbuvir/Velpatasvir in Patients With Chronic Hepatitis C Virus Infection Receiving Opioid Substitution Therapy: Analysis of Phase 3 ASTRAL Trials

Efficacy and Safety of Sofosbuvir/Velpatasvir in Patients With Chronic Hepatitis C Virus Infection Receiving Opioid Substitution Therapy: Analysis of Phase 3 ASTRAL Trials

Elimination of hepatitis C virus infection among PWID: The beginning of a new era of interferon-free DAA therapy

HCV Cure and Reinfection Among People With HIV/HCV Coinfection and People Who Inject Drugs

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