Efficacy and Safety of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir With or Without Ribavirin in Patients With Chronic Hepatitis C Virus Genotype 1 Infection Receiving Opioid Substitution Therapy: A Post Hoc Analysis of 12 Clinical Trials

Abstract Background We evaluated the impact of opioid substitution therapy (OST) on the completion, adherence, efficacy, and safety of the 3-direct-acting antiviral regimen of ombitasvir, paritaprevir (identified by AbbVie and Enanta) co-dosed with ritonavir, and dasabuvir ± ribavirin among patients infected with hepatitis C virus (HCV) genotype (GT) 1, with or without compensated cirrhosis. Methods Data were pooled from GT1-infected patients enrolled in 12 phase II/III/IIIb clinical trials and categorized by use of OST. Patients with ongoing drug use were excluded. HCV treatment completion, treatment adherence (≥90%), sustained virologic response at post-treatment week 12 (SVR12), and adverse events were assessed. Results Of 4747 patients, 3% (n = 149) received OST. Among patients receiving OST vs those not receiving OST, 82% (n = 122) vs 52% (n = 2409) had GT1a infection; 76% (n = 113) vs 61% (n = 2792) were treatment naïve; and 17% (n = 25) vs 18% (n = 830) had cirrhosis, respectively. The proportion of patients completing HCV treatment did not differ between those receiving and not receiving OST (97% [n = 144] vs 98% [n = 4510], respectively), whereas adherence to treatment was reduced in patients receiving vs those not receiving OST (88% [n = 105] vs 97% [n = 4057], respectively). SVR12 was similar between patients receiving and not receiving OST (94% [n = 140] vs 96% [n = 4405], respectively; P = .273). Treatment was well tolerated. Conclusions Although treatment adherence was lower in patients receiving OST vs those not receiving OST, treatment completion and SVR12 were similar between groups. These data support the use of direct-acting antiviral therapies in patients receiving OST.

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Response to direct-acting antiviral therapy among ongoing drug users and people receiving opioid substitution therapy

Journal of Hepatology ◽

10.1016/j.jhep.2019.02.018 ◽

2019 ◽

Vol 71 (1) ◽

pp. 45-51 ◽

Cited By ~ 14

Author(s):

Juan Macías ◽

Luis E. Morano ◽

Francisco Téllez ◽

Rafael Granados ◽

Antonio Rivero-Juárez ◽

...

Keyword(s):

Antiviral Therapy ◽

Drug Users ◽

Substitution Therapy ◽

Opioid Substitution Therapy ◽

Direct Acting Antiviral ◽

Direct Acting ◽

Opioid Substitution

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Safety and efficacy of Ombitasvir, Paritaprevir/Ritonavir and Dasabuvir with or without ribavirin in chronic hepatitis C patients receiving opioid substitution therapy: a pooled analysis across 12 clinical trials

Journal of Hepatology ◽

10.1016/s0168-8278(17)31430-7 ◽

2017 ◽

Vol 66 (1) ◽

pp. S514 ◽

Cited By ~ 15

Author(s):

J. Grebley ◽

M. Puoti ◽

H. Wedemeyer ◽

C. Cooper ◽

M.S. Sulkowski ◽

...

Keyword(s):

Clinical Trials ◽

Chronic Hepatitis ◽

Hepatitis C ◽

Chronic Hepatitis C ◽

Pooled Analysis ◽

Substitution Therapy ◽

Opioid Substitution Therapy ◽

Safety And Efficacy ◽

Chronic Hepatitis C Patients ◽

Opioid Substitution

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Efficacy of Direct-acting Antivirals for Chronic Hepatitis C Virus Infection in People Who Inject Drugs or Receive Opioid Substitution Therapy: A Systematic Review and Meta-analysis

Clinical Infectious Diseases ◽

10.1093/cid/ciz696 ◽

2019 ◽

Vol 70 (11) ◽

pp. 2355-2365 ◽

Cited By ~ 8

Author(s):

Christiana Graf ◽

Marcus M Mücke ◽

Georg Dultz ◽

Kai-Henrik Peiffer ◽

Alica Kubesch ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Treatment Outcomes ◽

People Who Inject Drugs ◽

Discontinuation Rate ◽

Direct Acting Antivirals ◽

Substitution Therapy ◽

Opioid Substitution Therapy ◽

Direct Acting ◽

Opioid Substitution

Abstract Background Treatment uptake for hepatitis C virus (HCV) infection in people who inject drugs (PWID) and patients on opioid substitution therapy (OST) is still low despite treatment guidelines that advocate the use of direct-acting antivirals (DAAs) in all patients. Our aim in this review was to investigate treatment outcomes among PWID and patients on OST in comparison to control cohorts. Methods A search of Embase, Medline, PubMed, and Web of Science (from October 2010 to March 2018) was conducted to assess sustained virologic response (SVR), discontinuation rates, adherence, and HCV reinfection in PWID and patients on OST. Results We identified 11 primary articles and 12 conference abstracts comprising 1702 patients on OST, 538 PWID, and 19 723 patients who served as controls. Among patients on OST, the pooled SVR was 90% (95% confidence interval [CI], 87% to 93%) and pooled treatment discontinuation rate was 7% (95% CI, 4% to 11%). Similarly, the pooled SVR was 88% (95% CI, 80% to 93%) in PWID and the pooled treatment discontinuation rate was 9% (95% CI, 5% to 15%). There was no significant difference regarding pooled rates of SVR, adherence, and discontinuation between patients on OST and controls as well as between PWID and controls. HCV reinfection rates among patients on OST ranged from 0.0 to 12.5 per 100 person-years. Conclusions HCV treatment outcomes in PWID and patients on OST are similar to those in patients without a history of injecting drugs, supporting current guideline recommendations to treat HCV in these patient populations.

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Direct-acting antiviral treatment of chronic HCV-infected patients on opioid substitution therapy: Still a concern in clinical practice?

Addiction ◽

10.1111/add.14128 ◽

2018 ◽

Vol 113 (5) ◽

pp. 868-882 ◽

Cited By ~ 30

Author(s):

Stefan Christensen ◽

Peter Buggisch ◽

Stefan Mauss ◽

Klaus H. W. Böker ◽

Eckart Schott ◽

...

Keyword(s):

Clinical Practice ◽

Antiviral Treatment ◽

Substitution Therapy ◽

Opioid Substitution Therapy ◽

Direct Acting Antiviral ◽

Chronic Hcv ◽

Direct Acting ◽

Opioid Substitution

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Sofosbuvir and velpatasvir in the treatment of chronic hepatitis C

Future Virology ◽

10.2217/fvl-2019-0104 ◽

2019 ◽

Vol 14 (11) ◽

pp. 715-727

Author(s):

Kelli Wuerth ◽

Tianna Magel ◽

Brian Conway

Keyword(s):

Clinical Trials ◽

Chronic Hepatitis ◽

Life Cycle ◽

Clinical Practice ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Hcv Treatment ◽

Real World Data ◽

Direct Acting Antiviral ◽

Direct Acting

Advances in hepatitis C virus (HCV) treatment led to the development of highly effective all oral direct acting antiviral regimens. The combination of sofosbuvir and velpatasvir (SOF/VEL), two agents acting synergistically at different stages in the viral life cycle, has been evaluated in a broad range of clinical trials supporting its efficacy in complex and diverse patient populations. Following regulatory approval in 2016, SOF/VEL has been widely used as a safe, effective pangenotypic regimen in clinical practice. In this review, we will discuss the current preclinical, clinical and real-world data on SOF/VEL.

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Sofosbuvir-Based Direct-Acting Antiviral Therapies for HCV in People Receiving Opioid Substitution Therapy: An Analysis of Phase 3 Studies

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy001 ◽

2018 ◽

Vol 5 (2) ◽

Cited By ~ 16

Author(s):

Jason Grebely ◽

Jordan J Feld ◽

David Wyles ◽

Mark Sulkowski ◽

Liyun Ni ◽

...

Keyword(s):

Adverse Events ◽

Treatment Completion ◽

Substitution Therapy ◽

Opioid Substitution Therapy ◽

Phase 3 ◽

Serious Adverse Events ◽

Direct Acting Antiviral ◽

Significant Difference ◽

Direct Acting ◽

Opioid Substitution

Abstract Background Hepatitis C virus (HCV) direct-acting antiviral therapy is effective among people receiving opioid substitution therapy (OST), but studies are limited by small numbers of nongenotype 1 (GT1) patients. The aim of this study was to evaluate the treatment completion, adherence, SVR12, and safety of sofosbuvir-based therapies in HCV patients receiving and not receiving OST. Methods Ten phase 3 studies of sofosbuvir-based regimens included ION (ledipasvir/sofosbuvir ± ribavirin for 8, 12, or 24 weeks in GT1), ASTRAL (sofosbuvir/velpatasvir for 12 weeks in GT1-6), and POLARIS (sofosbuvir/velpatasvir and sofosbuvir/velpatasvir/voxilaprevir in GT1-6). Patients with clinically significant drug use (last 12 months) or noncannabinoids detected at screening were ineligible. Results Among 4743 patients, 4% (n = 194) were receiving OST (methadone; n = 113; buprenorphine, n = 75; other, n = 6). Compared with those not receiving OST (n = 4549), those receiving OST (n = 194) were younger (mean age, 48 vs 54), more often male (73% vs 61%), GT3 (38% vs 17%), treatment-naïve (78% vs 65%), and cirrhotic (36% vs 23%). Among those receiving and not receiving OST, there was no significant difference in treatment completion (97% vs 99%, P = .06), SVR12 (94% vs 97%, P = .06), relapse (0.5% vs 2.1%, P = .19), adverse events (78% vs 77%, P = .79), or serious adverse events (3.6% vs 2.4%, P = .24). There was no difference in SVR12 in patients with cirrhosis (99% vs 95%, P = .25) or those with G3 (95% vs 95%, P = .77) in those receiving OST. Among patients receiving OST, SVR12 was high among those receiving methadone (95%) and buprenorphine (96%). Conclusion Sofosbuvir-based therapies are effective and safe in patients receiving OST.

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