Dataset Information

Effectiveness of Ledipasvir/Sofosbuvir and Sofosbuvir/Velpatasvir in People Who Inject Drugs and/or Those in Opioid Agonist Therapy.

ABSTRACT: We evaluated the effectiveness of ledipasvir/sofosbuvir (LDV/SOF) in treating hepatitis C virus (HCV) genotype 1 and SOF/velpatasvir (SOF/VEL) for all genotypes among people who inject drugs (PWID) and those not injecting drugs and who were on or off opioid agonist therapy (OAT). Study participants comprised a population-based cohort in British Columbia, Canada. The British Columbia Hepatitis Testers Cohort includes data on individuals tested for HCV from 1990 to 2016 that are integrated with medical visits, hospitalization, and prescription drug data. We classified study participants as off OAT/recent injection drug use (off-OAT/RIDU), off OAT/past IDU (off-OAT/PIDU), off OAT/no IDU (off-OAT/NIDU), on OAT/IDU (on-OAT/IDU), and on OAT/no IDU (on-OAT/NIDU). We assessed sustained virologic response (SVR) 10 weeks after HCV treatment among study groups treated with LDV/SOF or SOF/VEL until January 13, 2018. Analysis included 5,283 eligible participants: 390 off-OAT/RIDU, 598 off-OAT/PIDU, 3,515 off-OAT/NIDU, 609 on-OAT/IDU, and 171 on-OAT/NIDU. The majority were male patients (64%-74%) and aged ?50 years (58%-85%). The SVRs for off-OAT/RIDU, off-OAT/PIDU, off-OAT/NIDU, on-OAT/IDU, and on-OAT/NIDU were 91% (355/390), 95% (570/598), 96% (3,360/3,515), 93% (567/609), and 95% (163/171), respectively. Among those with no SVR, 14 individuals died while on treatment or before SVR assessment, including 4 from illicit drug overdose. In the overall multivariable model, off-OAT/RIDU, on-OAT/IDU, male sex, cirrhosis, treatment duration <8 weeks, treatment duration 8 weeks, and treatment with SOF/VEL were associated with not achieving SVR. Conclusion: In this large real-world cohort, PWID and/or those on OAT achieved high SVRs, although slightly lower than people not injecting drugs. This finding also highlights the need for additional measures to prevent loss to follow-up and overdose-related deaths among PWID.

SUBMITTER: Janjua NZ

PROVIDER: S-EPMC6442698 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Effectiveness of Ledipasvir/Sofosbuvir and Sofosbuvir/Velpatasvir in People Who Inject Drugs and/or Those in Opioid Agonist Therapy.

Janjua Naveed Z NZ Darvishian Maryam M Wong Stanley S Yu Amanda A Rossi Carmine C Ramji Alnoor A Yoshida Eric M EM Butt Zahid A ZA Samji Hasina H Chong Mei M Chapinal Nuria N Cook Darrel D Alvarez Maria M Tyndall Mark M Krajden Mel M

Hepatology communications 20190110 4

We evaluated the effectiveness of ledipasvir/sofosbuvir (LDV/SOF) in treating hepatitis C virus (HCV) genotype 1 and SOF/velpatasvir (SOF/VEL) for all genotypes among people who inject drugs (PWID) and those not injecting drugs and who were on or off opioid agonist therapy (OAT). Study participants comprised a population-based cohort in British Columbia, Canada. The British Columbia Hepatitis Testers Cohort includes data on individuals tested for HCV from 1990 to 2016 that are integrated with me ...[more]

PMID: 30976739

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Project description:BackgroundOpioid agonist treatment (OAT) reduces many of the harms associated with opioid dependence. We use mathematical modelling to comprehensively evaluate the overall health benefits of OAT in people who inject drugs in Perry County (KY, USA), Kyiv (Ukraine), and Tehran (Iran).MethodsWe developed a dynamic model of HIV and hepatitis C virus (HCV) transmission, incarceration, and mortality through overdose, injury, suicide, disease-related and other causes. The model was calibrated to site-specific data using Bayesian methods. We evaluated preventable drug-related deaths (deaths due to HIV, HCV, overdose, suicide, or injury) averted over 2020-40 for four scenarios, added incrementally, compared with a scenario without OAT: existing OAT coverage (setting-dependent; community 4-11%; prison 0-40%); scaling up community OAT to 40% coverage; increasing average OAT duration from 4-14 months to 2 years; and scaling up prison-based OAT.OutcomesDrug-related harms contributed differentially to mortality across settings: overdose contributed 27-47% (range of median projections) of preventable drug-related deaths over 2020-40, suicide 6-17%, injury 3-17%, HIV 0-59%, and HCV 2-18%. Existing OAT coverage in Tehran (31%) could have a substantial effect, averting 13% of preventable drug-related deaths, but will have negligible effect (averting <2% of preventable drug-related deaths) in Kyiv and Perry County due to low OAT coverage (<4%). Scaling up community OAT to 40% could avert 12-24% of preventable drug-related deaths, including 13-22% of overdose deaths, with greater effect in settings with significant HIV mortality (Tehran and Kyiv). Improving OAT retention and providing prison-based OAT would have a significant additional effect, averting 27-51% of preventable drug-related deaths.InterpretationOAT can substantially reduce drug-related harms, particularly in settings with HIV epidemics in people who inject drugs. Maximising these effects requires research and investment into achieving higher coverage and provision and longer retention of OAT in prisons and the community.FundingUK National Institute for Health Research, US National Institute on Drug Abuse.

Project description:BackgroundIn March 2020, following a provincial COVID-19 emergency declaration, modifications to opioid agonist treatment (OAT) were introduced in Ontario, Canada to promote treatment access amid the pandemic and ongoing opioid overdose crisis. Modifications included federal exemptions to facilitate OAT prescription re-fills, extensions, and deliveries and interim treatment guidance emphasizing take-home (non-observed) doses and reduced urine drug screening for OAT patients.MethodsWe conducted an interrupted time series study using health administrative data from September 17th, 2019-September 21st, 2020, on 359 people who inject drugs with suspected opioid use disorder in Toronto, Ontario. We used segmented regression analyses to evaluate the joint effects of the provincial COVID-19 emergency declaration, federal OAT exemptions, and interim treatment guidance-all implemented between March 17th-23rd, 2020-on the weekly proportion of participants enrolled in OAT (i.e., ≥1 day(s) covered with methadone or buprenorphine/naloxone), with an opioid-related overdose (based on emergency department visits and hospitalizations), and who died (all-cause), and the weekly proportion of OAT-enrolled participants receiving take-home doses (i.e., ≥1 day(s) covered) and undergoing urine drug screening.ResultsPost-implementation, the interventions were associated with immediate absolute changes in OAT enrollment (+1.95%; 95% CI=0.04%-3.85%), receipt of take-home doses (+18.3%; 95% CI=13.2%-23.4%), and urine drug screening (-22.4%; 95% CI=[-26.9%]-[-17.9%]) and a gradual absolute increase of 0.56% in urine drug screening week-to-week (95% CI=0.27%-0.86%) beyond the pre-implementation trend. At 26 weeks post-implementation, OAT enrollment and urine drug screening approached pre-implementation levels whereas the increase in take-home doses was largely sustained (+15.0%; 95% CI=4.33%-25.6%). No post-implementation increases in opioid-related overdoses were observed. Death was not modelled (low event frequency).ConclusionChanges to OAT provision following provincial COVID-19 restrictions were associated with an immediate and sustained increase in take-home dose coverage among OAT-enrolled participants, without corresponding increases in opioid-related overdoses among all participants.

Project description:Background & aimsVoxilaprevir/velpatasvir/sofosbuvir (VOX/VEL/SOF) is highly effective for re-treatment of direct-acting antiviral (DAA)-experienced patients with chronic HCV infection. In the present study, predictors of virologic treatment response were analyzed in an integrative analysis of three large real-world cohorts.MethodsConsecutive patients re-treated with VOX/VEL/SOF after DAA failure were enrolled between 2016 and 2021 in Austria, Belgium, Germany, Italy, Spain and Switzerland.ResultsA total of 746 patients were included: median age was 56 (16-88) years and 77% were male. Most patients were infected with HCV genotype 1 (56%) and 3 (32%). 86% of patients carried resistance-associated substitutions in the NS3, NS5A or NS5B regions. Overall, 95.4% (683/716) of patients achieved a sustained virologic response. Treatment effectiveness was significantly affected by advanced liver disease (p <0.001), hepatocellular carcinoma (p <0.001), higher baseline ALT levels (p = 0.02), HCV genotype 3 (p <0.001), and prior VEL/SOF treatment (p = 0.01). In a multivariate analysis, only HCV genotype 3, hepatocellular carcinoma and cirrhosis turned out to be independent predictors of treatment failure. Resistance-associated substitutions, as well as the presence of rare genotypes, did not impact treatment outcome. The effectiveness of rescue therapy with glecaprevir/pibrentasvir and SOF, with or without ribavirin, for 12 to 24 weeks was found to be high (100%).ConclusionsInfection with HCV genotype 3, the presence of liver cancer and cirrhosis are independently associated with failure of VOX/VEL/SOF re-treatment. It is unclear whether the addition of ribavirin and/or extension of treatment duration may be effective to avoid virologic relapse on VOX/VEL/SOF. However, rescue treatment with glecaprevir/pibrentasvir+SOF seems to be effective.Impact and implicationsRepresentative data on the effectiveness of voxilaprevir/velpatasvir/sofosbuvir (VOX/VEL/SOF) in clinical practice are still scarce and the collection of a larger number of patients with difficult-to-treat cofactors including the assessment of resistance-associated substitution profiles is required before more specific recommendations for optimal re-treatment in these patients can be given. Thus, we aimed to analyze treatment effectiveness and predictors of virologic response to VOX/VEL/SOF in an integrative analysis of three large real-word cohorts. The study results, derived from a multicenter cohort consisting of 746 patients, demonstrated that re-treatment with VOX/VEL/SOF is an effective salvage therapy associated with an overall per protocol sustained virologic response rate of 95%. Hepatocellular carcinoma onset, cirrhosis and HCV genotype 3 were identified as independent negative predictors of treatment response, whereas resistance-associated substitutions, as well as rare genotypes and chimera, did not impact sustained virologic response rates following re-treatment with VOX/VEL/SOF.

Dataset Information

Effectiveness of Ledipasvir/Sofosbuvir and Sofosbuvir/Velpatasvir in People Who Inject Drugs and/or Those in Opioid Agonist Therapy.

Publications

Effectiveness of Ledipasvir/Sofosbuvir and Sofosbuvir/Velpatasvir in People Who Inject Drugs and/or Those in Opioid Agonist Therapy.

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