Adherence to sofosbuvir and velpatasvir among people with chronic HCV infection and recent injection drug use

Background : This study investigated treatment adherence among people with recent injecting drug use in a study of sofosbuvir/velpatasvir therapy for HCV infection. Methods : SIMPLIFY is an international open-label, single-arm multicentre study that recruited participants with recent injecting drug use (previous six months) and chronic HCV genotype (G) 1-6 infection between March and October, 2016 in seven countries (19 sites). Participants received sofosbuvir/velpatasvir once-daily for 12 weeks administered in a one-week electronic blister pack (records the time and date of each dose) for 12 weeks. We evaluated non-adherence (<90% adherent) as measured by electronic blister-pack assessed using logistic regression and generalised estimating equations (continuous) with detailed analyses of dosing dynamics. Results : Among 103 participants, 97% (n=100) completed treatment. Median adherence to therapy was 94%. Overall, 32% (n=33) were considered non-adherent (<90% adherence). Adherence significantly decreased over the course of therapy. Recent stimulant injecting (cocaine and/or amphetamines) at treatment initiation and during treatment was independently associated with non-adherence. Inconsistent dose timing (standard deviation of daily dose timing of ≥ 240 minutes) was also independently associated with non-adherence to therapy. Factors associated with inconsistent dose timing included lower levels of education and recent stimulant injecting. SVR was similar among adherent and non-adherent populations (94% vs. 94%, P =0.944). Conclusion : This study demonstrated high adherence to once-daily sofosbuvir/velpatasvir therapy among a population of people with recent injecting drug use. Recent stimulant injecting prior to and during DAA therapy and inconsistent dose-timing during treatment was associated with non-adherence. However, there was no impact of non-adherence on response to therapy, suggesting that adherence is not a significant barrier to successful DAA therapy in people with recent injecting drug use.

[1]  S. Sockalingam,et al.  Understanding real-world adherence in the directly acting antiviral era: A prospective evaluation of adherence among people with a history of drug use at a community-based program in Toronto, Canada. , 2017, The International journal on drug policy.

[2]  B. Conway,et al.  Efficacy of response-guided directly observed pegylated interferon and self-administered ribavirin for people who inject drugs with hepatitis C virus genotype 2/3 infection: The ACTIVATE study. , 2017, The International journal on drug policy.

[3]  G. Dore,et al.  Direct-acting antiviral agents for HCV infection affecting people who inject drugs , 2017, Nature Reviews Gastroenterology & Hepatology.

[4]  J. Lazarus,et al.  Restrictions for reimbursement of interferon-free direct-acting antiviral therapies for HCV infection in Europe , 2017 .

[5]  C. Van Steenkiste,et al.  Belgian experience with direct acting antivirals in people who inject drugs. , 2017, Drug and alcohol dependence.

[6]  Brian L. Pearlman,et al.  Efficacy of 8 Weeks of Sofosbuvir, Velpatasvir, and Voxilaprevir in Patients With Chronic HCV Infection: 2 Phase 3 Randomized Trials. , 2017, Gastroenterology.

[7]  S. Norris,et al.  Outcomes from a large 10 year hepatitis C treatment programme in people who inject drugs: No effect of recent or former injecting drug use on treatment adherence or therapeutic response , 2017, PloS one.

[8]  B. Conway,et al.  Adherence to response-guided pegylated interferon and ribavirin for people who inject drugs with hepatitis C virus genotype 2/3 infection: the ACTIVATE study , 2017, BMC Infectious Diseases.

[9]  G. Dore,et al.  HCV Cure and Reinfection Among People With HIV/HCV Coinfection and People Who Inject Drugs , 2017, Current HIV/AIDS Reports.

[10]  Joseph K. Lim,et al.  Medicaid Reimbursement for Oral Direct Antiviral Agents for the Treatment of Chronic Hepatitis C , 2017, The American Journal of Gastroenterology.

[11]  Guangdi Li,et al.  Current therapy for chronic hepatitis C: The role of direct-acting antivirals , 2017, Antiviral Research.

[12]  A. Mangia,et al.  Efficacy and Safety of Sofosbuvir/Velpatasvir in Patients With Chronic Hepatitis C Virus Infection Receiving Opioid Substitution Therapy: Analysis of Phase 3 ASTRAL Trials. , 2016, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[13]  G. Dore,et al.  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. , 2016, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[14]  M. Hellard,et al.  Sofosbuvir and ribavirin for 6 weeks is not effective among people with recent hepatitis C virus infection: The DARE‐C II study , 2016, Hepatology.

[15]  M. Proschan,et al.  High adherence to all-oral directly acting antiviral HCV therapy among an inner-city patient population in a phase 2a study , 2015, Hepatology International.

[16]  G. Dore,et al.  Restrictions for Medicaid Reimbursement of Sofosbuvir for the Treatment of Hepatitis C Virus Infection in the United States , 2015, Annals of Internal Medicine.

[17]  M. King,et al.  Ombitasvir/paritaprevir/r and dasabuvir plus ribavirin in HCV genotype 1-infected patients on methadone or buprenorphine. , 2015, Journal of hepatology.

[18]  Dawid Pieper,et al.  Factors influencing adherence in Hepatitis-C infected patients: a systematic review , 2014, BMC Infectious Diseases.

[19]  M. Hellard,et al.  Treatment of hepatitis C virus infection among people who are actively injecting drugs: a systematic review and meta-analysis. , 2013, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[20]  D. D. Des Jarlais,et al.  Determinants of hepatitis C virus treatment completion and efficacy in drug users assessed by meta-analysis. , 2013, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[21]  M. Alavi,et al.  Adherence to treatment for recently acquired hepatitis C virus (HCV) infection among injecting drug users. , 2011, Journal of hepatology.

[22]  Tania B. Huedo-Medina,et al.  Adherence to Highly Active Antiretroviral Therapy (HAART): A Meta-Analysis , 2011, AIDS and Behavior.

[23]  P. Marcellin,et al.  Adherence to treatment and quality of life during hepatitis C therapy: a prospective, real‐life, observational study , 2011, Liver international : official journal of the International Association for the Study of the Liver.

[24]  G. Papatheodoridis,et al.  Substitution treatment or active intravenous drug use should not be contraindications for antiviral treatment in drug users with chronic hepatitis C , 2010, Liver international : official journal of the International Association for the Study of the Liver.

[25]  K. Mimidis,et al.  Should active injecting drug users receive treatment for chronic hepatitis C? , 2010, Arquivos de gastroenterologia.

[26]  G. Foster,et al.  Community‐based treatment for chronic hepatitis C in drug users: high rates of compliance with therapy despite ongoing drug use , 2009, Alimentary pharmacology & therapeutics.

[27]  D. Sylvestre,et al.  Adherence to hepatitis C treatment in recovering heroin users maintained on methadone , 2007, European journal of gastroenterology & hepatology.

[28]  B. Clotet,et al.  Poor response to hepatitis C virus (HCV) therapy in HIV- and HCV-coinfected patients is not due to lower adherence to treatment. , 2006, AIDS research and human retroviruses.

[29]  P. Read,et al.  Efficacy and safety of sofosbuvir/velpatasvir in people with chronic hepatitis C virus infection and recent injecting drug use: the SIMPLIFY study , 2017 .

[30]  A. Mangia,et al.  On-Treatment Illicit Drug Use Did Not Impact Treatment Outcome during Therapy with Ledipasvir-Sofosbuvi with or without Ribavirin in the Phase 3 ION-1 Study , 2016 .

[31]  C. Cooper,et al.  ABT-450/r/Ombitasvir plus Dasabuvir With or Without Ribavirin in HCV Genotype 1-infected Patients Receiving Stable Opioid Substitution Treatment: Pooled Analysis of Efficacy and Safety in Phase 2 and Phase 3 Trials , 2014 .