scholarly journals Low Hepatitis C Reinfection Following Direct-acting Antiviral Therapy Among People Who Inject Drugs on Opioid Agonist Therapy

2019 ◽  
Vol 70 (12) ◽  
pp. 2695-2702 ◽  
Author(s):  
Matthew J Akiyama ◽  
Daniel Lipsey ◽  
Moonseong Heo ◽  
Linda Agyemang ◽  
Brianna L Norton ◽  
...  

Abstract Background Direct-acting antiviral (DAA) therapy is highly effective in people who inject drugs (PWID); however, rates, specific injection behaviors, and social determinants associated with hepatitis C virus (HCV) reinfection following DAA therapy among PWID on opioid agonist therapy (OAT) are poorly understood. Methods PREVAIL was a randomized controlled trial that assessed models of HCV care for 150 PWID on OAT. Those who achieved sustained virologic response (SVR) (n = 141; 94%) were eligible for this extension study. Interviews and assessments of recurrent HCV viremia occurred at 6-month intervals for up to 24 months following PREVAIL. We used survival analysis to analyze variables associated with time to reinfection. Results Of 141 who achieved SVR, 114 had a least 1 visit in the extension study (62% male; mean age, 52 years). Injection drug use (IDU) was reported by 19% (n = 22) in the extension study. HCV reinfection was observed in 3 participants. Over 246 person-years of follow-up, the incidence of reinfection was 1.22/100 person-years (95% CI, 0.25–3.57). All reinfections occurred among participants reporting ongoing IDU. The incidence of reinfection in participants reporting ongoing IDU (41 person-years of follow-up) was 7.4/100 person-years (95% CI, 1.5–21.6). Reinfection was associated with reporting ongoing IDU in the follow-up period (P < .001), a lack confidence in the ability to avoid contracting HCV (P < .001), homelessness (P = .002), and living with a PWID (P = .007). Conclusions HCV reinfection was low overall, but more common among people with ongoing IDU following DAA therapy on OAT, as well as those who were not confident in the ability to avoid contracting HCV, homeless, or living with a PWID. Interventions to mediate these risk factors following HCV therapy are warranted.

2020 ◽  
Vol 222 (3) ◽  
pp. 488-498 ◽  
Author(s):  
Matthew J Akiyama ◽  
Daniel Lipsey ◽  
Lilia Ganova-Raeva ◽  
Lili T Punkova ◽  
Linda Agyemang ◽  
...  

Abstract Background Understanding hepatitis C virus (HCV) transmission among people who inject drugs (PWID) is essential for HCV elimination. We aimed to differentiate reinfections from treatment failures and to identify transmission linkages and associated factors in a cohort of PWID receiving opioid agonist therapy (OAT). Methods We analyzed baseline and follow-up specimens from 150 PWID from 3 OAT clinics in the Bronx, New York. Next-generation sequencing data from the hypervariable region 1 of HCV were analyzed using Global Hepatitis Outbreak and Surveillance Technology. Results There were 3 transmission linkages between study participants. Sustained virologic response (SVR) was not achieved in 9 participants: 7 had follow-up specimens with similar sequences to baseline, and 2 died. In 4 additional participants, SVR was achieved but the participants were viremic at later follow-up: 2 were reinfected with different strains, 1 had a late treatment failure, and 1 was transiently viremic 17 months after treatment. All transmission linkages were from the same OAT clinic and involved spousal or common-law partnerships. Conclusion This study highlights the use of next-generation sequencing as an important tool for identifying viral transmission and to help distinguish relapse and reinfection among PWID. Results reinforce the need for harm reduction interventions among couples and those who report ongoing risk factors after SVR.


2020 ◽  
Author(s):  
Christer F. Aas ◽  
Jørn Henrik Vold ◽  
Svetlana Skurtveit ◽  
Ingvild Odsbu ◽  
Fatemeh Chalabianloo ◽  
...  

Abstract Background: Treatment with direct-acting antiviral agents (DAAs) offers an opportunity to eliminate hepatitis C virus (HCV) endemic among people who inject drugs (PWID) and people enrolled in opioid agonist therapy (OAT) programs. The objective of this study was to estimate and to compare HCV treatment uptake after the introduction of DAAs among patients receiving OAT in Sweden and Norway. We also aimed to evaluate predictors of DAAs treatment among OAT patients in both countries.Methods: This observational study was conducted with data from The Swedish Prescribed Drug Register and The Norwegian Prescription Database. We studied dispensed medications to calculate HCV treatment among OAT patients from 2014 to 2017 in Sweden and Norway. HCV prevalence was estimated from primary and secondary sources. Dispensations of medicines from different therapeutic areas, which served as proxy for co-morbidities in 2017, were conditionally adjusted for age, gender, and OAT medications. Logistic regression was used to evaluate these parameters. Results: In total 3,529 individuals were identified with dispensed OAT in the Swedish cohort and 7,739 individuals in the Norwegian cohort. HCV treatment was utilized by 407 persons in Sweden and 920 in Norway during the study period. Annual HCV and DAA treatment uptake increased in both countries. The estimated cumulative HCV treatment uptake at the end of 2017 was 31% in Norway and 28% in Sweden. DAA treatment was associated with increased age (aOR 1.8; 95% CI 1.0-3.2) and the dispensation of drugs used for diabetes (aOR 3.2; 95% CI 1.8-5.7) in Sweden. In Norway, lipid modifying agents and antibacterials were associated with decreased odds (aOR 0.4; 95%CI 0.2-0.9, aOR 0.8; 95%CI 0.6-1.0).Conclusions: An increase in DAA treatment and HCV treatment uptake was observed among Swedish and Norwegian OAT patients whilst introducing new direct-acting antiviral treatment regimens. However, more than two thirds of the OAT population in Norway and Sweden were untreated at the beginning of 2018. A further scale-up is crucial in order to control and eliminate the HCV endemic among OAT patients.


2019 ◽  
Vol 71 (7) ◽  
pp. e115-e124 ◽  
Author(s):  
Evan B Cunningham ◽  
Behzad Hajarizadeh ◽  
Janaki Amin ◽  
Alain H Litwin ◽  
Edward Gane ◽  
...  

Abstract Background This study investigated adherence and associated factors among people with recent injection drug use (IDU) or current opioid agonist therapy (OAT) and compared once-daily to twice-daily hepatitis C virus (HCV) direct-acting antiviral (DAA) therapy. Methods SIMPLIFY and D3FEAT are international, multicenter studies that recruited participants with recent IDU (previous 6 months; SIMPLIFY, D3FEAT) or current OAT (D3FEAT) between March 2016 and February 2017 in 8 countries. Participants received sofosbuvir/velpatasvir (once daily; SIMPLIFY) or paritaprevir/ritonavir/ombitasvir, dasabuvir (twice daily) ± ribavirin (D3FEAT) for 12 weeks administered in electronic blister packs. We evaluated overall adherence (proportion of prescribed doses taken) and nonadherence (<90% adherent) between dosing patterns. Results Of 190 participants, 184 (97%) completed treatment. Median adherence was 92%, with higher adherence among those receiving once-daily vs twice-daily therapy (94% vs 87%, P = .005). Overall, 40% of participants (n = 76) were nonadherent (<90% adherent). Recent stimulant injecting (odds ratio [OR], 2.48 [95% confidence interval {CI}, 1.28–4.82]), unstable housing (OR, 2.18 [95% CI, 1.01–4.70]), and twice-daily dosing (OR, 2.81 [95% CI, 1.47–5.36]) were associated with nonadherence. Adherence decreased during therapy. Sustained virologic response was high in nonadherent (89%) and adherent populations (95%, P = .174), with no difference in SVR between those who did and did not miss 7 consecutive doses (92% vs 93%, P = .897). Conclusions This study demonstrated high adherence to once- and twice-daily DAA therapy among people with recent IDU or currently receiving OAT. Nonadherence described did not impact treatment outcomes, suggesting forgiveness to nonadherence.


2020 ◽  
Author(s):  
Christer frode Aas ◽  
Jørn Henrik Vold ◽  
Svetlana Skurtveit ◽  
Ingvild Odsbu ◽  
Fatemeh Chalabianloo ◽  
...  

Abstract Background Treatment with direct-acting antiviral agents (DAAs) offers an opportunity to eliminate hepatitis C virus (HCV) endemic among people who inject drugs (PWID) and people enrolled in opioid agonist therapy (OAT) programs. The objective of this study was to estimate and to compare HCV treatment uptake after the introduction of DAAs among patients receiving OAT in Sweden and Norway. We also aimed to evaluate predictors of DAAs treatment among OAT patients in both countries. Methods This observational study was conducted with data from The Swedish Prescribed Drug Register and The Norwegian Prescription Database. We studied dispensed medications to calculate cumulative frequency of HCV treatment among OAT patients from 2014 to 2017 in Sweden and Norway. Dispensations of medicines from different therapeutic areas, which served as proxy for co-morbidities in 2017, were adjusted for age, gender, and OAT medications and studied in a logistic regression model. Results In total 3,529 individuals were identified with dispensed OAT in the Swedish cohort and 7,739 individuals in the Norwegian cohort. HCV treatment was utilized by 407 persons in Sweden and 920 in Norway during the study period. Annual HCV treatment uptake increased in both countries, giving a cumulative frequency of around one-third in both countries at the end of the study period. DAA treatment was associated with increased age (aOR 1.8; 95% CI 1.0-3.2) and dispensation of drugs used for diabetes (aOR 3.2; 95% CI 1.8-5.7) in Sweden. In Norway, lipid modifying agents and antibacterials were associated with decreased odds (aOR 0.4; 95%CI 0.2-0.9, aOR 0.8; 95%CI 0.6-1.0). Conclusions An increase in DAA treatment and HCV treatment uptake was observed among Swedish and Norwegian OAT patients during the introduction period of new direct-acting treatment regimens. However, a further scale-up is crucial to be able to control and eliminate the HCV endemic among OAT patients.


2020 ◽  
Author(s):  
Christer F. Aas ◽  
Jørn Henrik Vold ◽  
Svetlana Skurtveit ◽  
Ingvild Odsbu ◽  
Fatemeh Chalabianloo ◽  
...  

Abstract Background Treatment with direct-acting antiviral agents (DAAs) offers an opportunity to eliminate hepatitis C virus (HCV) endemic among people who inject drugs (PWID) and people enrolled in opioid agonist therapy (OAT) programs. The objective of this study was to estimate and to compare HCV treatment uptake after the introduction of DAAs among patients receiving OAT in Sweden and Norway. We also aimed to evaluate predictors of DAAs treatment among OAT patients in both countries. Methods This observational study was conducted with data from The Swedish Prescribed Drug Register and The Norwegian Prescription Database. We studied dispensed medications to calculate HCV treatment among OAT patients from 2014 to 2017 in Sweden and Norway. HCV prevalence was estimated from primary and secondary sources. Dispensations of medicines from different therapeutic areas, which served as proxy for co-morbidities in 2017, were conditionally adjusted for age, gender, and OAT medications. Logistic regression was used to evaluate these parameters. Results In total 3,529 individuals were identified with dispensed OAT in the Swedish cohort and 7,739 individuals in the Norwegian cohort. HCV treatment was utilized by 407 persons in Sweden and 920 in Norway during the study period. Annual HCV and DAA treatment uptake increased in both countries. The estimated cumulative HCV treatment uptake at the end of 2017 was 31% in Norway and 28% in Sweden. DAA treatment was associated with increased age (aOR 1.8; 95% CI 1.0-3.2) and dispensation of drugs used for diabetes (aOR 3.2; 95% CI 1.8-5.7) in Sweden. In Norway, lipid modifying agents and antibacterials were associated with decreased odds (aOR 0.4; 95%CI 0.2-0.9, aOR 0.8; 95%CI 0.6-1.0). Conclusions An increase in DAA treatment and HCV treatment uptake was observed among Swedish and Norwegian OAT patients during the introduction period of new direct-acting treatment regimens. However, more than two thirds of the OAT population in Norway and Sweden were untreated at the beginning of 2018. A further scale-up is crucial to be able to control and eliminate the HCV endemic among OAT patients.


Author(s):  
Moonseong Heo ◽  
Irene Pericot-Valverde ◽  
Lior Rennert ◽  
Matthew J Akiyama ◽  
Brianna L Norton ◽  
...  

Abstract Background Adequate medication adherence is critical for achieving sustained viral response (SVR) of hepatitis C virus (HCV) among people who inject drugs (PWID). However, it is less known which patterns of direct-acting antiviral (DAA) treatment adherence are associated with SVR in this population or what factors are associated with each pattern. Methods The randomized three-arm PREVAIL study utilized electronic blister packs to obtain daily time frame adherence data in opiate agonist therapy program settings. Exact logistic regressions were applied to test the associations between SVR and six types of treatment adherence patterns. Results Of the 113 participants treated with combination DAAs, 109 (96.5%) achieved SVR. SVR was significantly associated with all pattern parameters except for number of switches between adherent and missed days: total adherent daily doses (exact AOR=1.12; 95%CI=1.04-1.22), percent total doses (1.09; 1.03-1.16), days on treatment (1.16; 1.05-1.32), maximum consecutive adherent days (1.34; 1.06-2.04), maximum consecutive non-adherent days (.85; .74-.95=.003). SVR was significantly associated with total adherent doses in the first two months of treatment, it was not in the last month. Compared to White participants (30.7±11.8(se)), Black (18.4±7.8) and Hispanic participants (19.2±6.1) had significantly shorter maximum consecutive adherent days. While alcohol intoxication was significantly associated with frequent switches, drug use was not associated with any adherence pattern. Conclusion Consistent maintenance of adequate total dose adherence over the entire course of HCV treatment is important in achieving SVR among PWID. Additional integrative addiction and medical care may be warranted for treating PWID experiencing alcohol intoxication.


2020 ◽  
Vol 7 (10) ◽  
Author(s):  
Jackie Habchi ◽  
Aurielle M Thomas ◽  
Sophie Sprecht-Walsh ◽  
Elenita Arias ◽  
Jeffrey Bratberg ◽  
...  

Abstract Background A minority of patients with opioid use disorder are treated for hepatitis C virus infection (HCV). While colocated HCV and opioid agonist therapy (OAT) along with harm reduction can facilitate prevention and cascade to cure, there are few real-world examples of such embedded care models in the United States in the direct-acting antiviral (DAA) era. Methods We conducted a retrospective chart review to determine sustained virologic response (SVR) and reinfection rates during the first 5-year period of DAA availability among individuals tested and treated on-site at Rhode Island’s only nonprofit methadone maintenance program. Results Of 275 who initiated DAAs, the mean age (range) was 43 (22–71) years, 34.5% were female, 57.5% had genotype 1a, 23.3% had cirrhosis, and 92% were Medicaid recipients. SVR was 85.0% (232/273), while modified intent-to-treat SVR was 93.2% (232/249); 17 patients did not achieve SVR, 2 awaited SVR 12 weeks post-end-of-treatment, and 24 were lost to follow-up. Thirty reinfections were identified over 375.5 person-years of follow-up (rate, 7.99/100 person-years). The median time to first reinfection (interquartile range) was 128 (85.25–202.5) days. Before July 1, 2018, 72 patients accessed DAAs over 3.7 years; after Medicaid DAA restrictions were lifted, 109 patients accessed DAAs over 1.3 years. The Prior Authorization (PA) process requires many steps, differing across 11 RI insurers, taking 45–120 minutes per patient. Conclusions DAA treatment was effective among a marginalized population in an urban colocated OAT/HCV program. Removing DAA restrictions facilitates treatment initiation. The PA process remains a modifiable barrier to expanding capacity in the United States.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Lars T. Fadnes ◽  
◽  
Christer Frode Aas ◽  
Jørn Henrik Vold ◽  
Christian Ohldieck ◽  
...  

Abstract Background A large proportion of people who inject drugs (PWID) living with hepatitis C virus (HCV) infection have not been treated. It is unknown whether inclusion of HCV diagnostics and treatment into integrated substance use disorder treatment and care clinics will improve uptake and outcome of HCV treatment in PWID. The aim is to assess the efficacy of integrating HCV treatment to PWID and this paper will present the protocol for an ongoing trial. Methods INTRO-HCV is a multicentre, randomised controlled clinical trial that will compare the efficacy of integrated treatment of HCV in PWID with the current standard treatment. Integrated treatment includes testing for HCV, assessing liver fibrosis with transient elastography, counselling, treatment delivery, follow-up and evaluation provided by integrated substance use disorder treatment and care clinics. Most of these clinics for PWID provide opioid agonist therapy while some clinics provide low-threshold care without opioid agonist therapy. Standard care involves referral to further diagnostics, treatment and treatment follow-up given in a hospital outpatient clinic with equivalent medications. The differences between the delivery platforms in the two trial arms involve use of a drop-in approach rather than specific appointment times, no need for additional travelling, less blood samples taken during treatment, and treatment given from already known clinicians. The trial will recruit approximately 200 HCV infected individuals in Bergen and Stavanger, Norway. The primary outcomes are time to treatment initiation and sustained virologic response, defined as undetectable HCV RNA 12 weeks after end of treatment. Secondary outcomes are cost-effectiveness, treatment adherence, changes in quality of life, fatigue and psychological well-being, changes in drug use, infection related risk behaviour, and risk of reinfection. The target group is PWID with HCV diagnosed receiving treatment and care within clinics for PWID. Discussion This study will inform on the effects of an integrated treatment program for HCV in clinics for PWID compared to standard care aiming to increase access to treatment and improving treatment adherence. If the integrated treatment model is found to be safe and efficacious, it can be considered for further scale-up. Trial registration ClinicalTrials.gov.no. NCT03155906.


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