Risk of Late Relapse or Reinfection With Hepatitis C Virus After Achieving a Sustained Virological Response: A Systematic Review and Meta-analysis

Simmons, Bryony; Saleem, Jawaad; Hill, Andrew; Riley, Richard D; Cooke, G.

doi:10.1093/cid/civ948

Cited by 266 publications

(235 citation statements)

References 52 publications

(14 reference statements)

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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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“…A newly published comprehensive metaanalysis [150] included 14 articles or conference abstracts among PWID or prisoners and 4 studies of HIV/HCV co-infected individuals from heterogeneous populations. Among a total of 771 PWID or prisoners, 42 cases of HCV RNA recurrence after SVR were observed.…”

Section: Incidence Of Hcv Reinfection After Svr Among Pwidmentioning

confidence: 99%

HCV epidemiology in high-risk groups and the risk of reinfection

Midgard

Weir

Palmateer

et al. 2016

Journal of Hepatology

155

100

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Injecting risk behaviours among people who inject drugs (PWID) and high-risk sexual practices among men who have sex with men (MSM) are important routes of hepatitis C virus (HCV) transmission. Current direct-acting antiviral treatment offers unique opportunities for reductions in HCV-related liver disease burden and epidemic control in high-risk groups, but these prospects could be counteracted by HCV reinfection due to on-going risk behaviours after successful treatment. Based on existing data from small and heterogeneous studies of interferon-based treatment, the incidence of reinfection after sustained virological response range from 2-6/100 person years among PWID to 10-15/100 person years among human immunodeficiency virus-infected MSM. These differences mainly reflect heterogeneity in study populations with regards to risk behaviours, but also reflect variations in study designs and applied virological methods. Increasing levels of reinfection are to be expected as we enter the interferon-free treatment era. Individual- and population-level efforts to address and prevent reinfection should therefore be undertaken when providing HCV care for people with on-going risk behaviour. Constructive strategies include acknowledgement, education and counselling, harm reduction optimization, scaled-up treatment including treatment of injecting networks, post-treatment screening, and rapid retreatment of reinfections.

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“…In a meta-analysis of reinfections after SVR (with IFN and/or DAAs) among people who inject drugs (PWIDs) and prisoners, the 5-year reinfection rate was 1.9/100 person-years (95% CI: 11.4-28.2) [43]. Another recent meta-analysis estimated the 5-year risk of HCV reinfection among ''high risk" groups to be 10.7% (95% CI, 6.4-15.7) and among HIV-HCV coinfected patients to be 15.0% (95% CI, 0.0%-48.3%) [43]. Most studies report rates of 1-5/100 person-years [43][44][45].…”

Section: Prevention Of Reinfectionmentioning

confidence: 99%

“…Another recent meta-analysis estimated the 5-year risk of HCV reinfection among ''high risk" groups to be 10.7% (95% CI, 6.4-15.7) and among HIV-HCV coinfected patients to be 15.0% (95% CI, 0.0%-48.3%) [43]. Most studies report rates of 1-5/100 person-years [43][44][45]. The rates of reinfection are higher among those who returned to drug use vs. those with a history of injection drug [44].…”

Section: Prevention Of Reinfectionmentioning

confidence: 99%

Management of the patient with SVR

Terrault

Hassanein

2016

Journal of Hepatology

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In the current era of therapy with direct-acting antiviral (DAAs) drugs, achievement of a sustained virological response (SVR) is achievable in ⩾90% of hepatitis C-infected patients. SVR benefits are well-recognized with reductions in rates of liver complications, hepatocellular carcinoma and mortality. Additional benefits include reduced morbidity related to extrahepatic and systemic manifestations of hepatitis C such as renal, dermatologic, and metabolic complications. However, not all patients will derive all of these benefits and monitoring for progression is necessary, especially in those with more advanced fibrosis. To maximize the health benefits of SVR, counseling patients on best means to maintain good liver health and prevent reinfection are also important.

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Risk of Late Relapse or Reinfection With Hepatitis C Virus After Achieving a Sustained Virological Response: A Systematic Review and Meta-analysis

Abstract: Sustained virological response is durable in patients treated for hepatitis C virus. Recurrence rates are generally low but increase in patient populations with risk factors for reinfection. The evidence supports the notion that risk of recurrence is driven by reinfection.

Cited by 266 publications

References 52 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

HCV epidemiology in high-risk groups and the risk of reinfection

Management of the patient with SVR

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