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Competing Interests: Potential conflicts of interest. The author reports personal fees from Abbott, AbbVie, Cepheid, Gilead Sciences, and Roche and grants from AbbVie, bioLytical, Cepheid, Gilead Sciences, and Hologic, outside the submitted work. The author has submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Background: Injection drug use (IDU) following treatment for hepatitis C virus (HCV) infection may lead to reinfection, particularly if access to harm reduction services is suboptimal. This study assessed HCV reinfection risk following direct-acting antiviral therapy within Australian prisons that had opioid agonist therapy (OAT) programs but did not have needle and syringe programs (NSPs)., Methods: The Surveillance and Treatment of Prisoners With Hepatitis C (SToP-C) study enrolled people incarcerated in 4 prisons between 2014 and 2019. Participants treated for HCV were followed every 3-6 months to identify reinfection (confirmed by sequencing). Reinfection incidence and associated factors were evaluated., Results: Among 388 participants receiving treatment, 161 had available posttreatment follow-up and were included in analysis (92% male; median age, 33 years; 67% IDU in prison; median follow-up 9 months). Among those with recent (in the past month) IDU (n = 71), 90% had receptive needle/syringe sharing. During 145 person-years (PY) of follow-up, 18 cases of reinfection were identified. Reinfection incidence was 12.5/100 PY (95% confidence interval [CI]: 7.9-19.8) overall, increasing to 28.7/100 PY (95% CI: 16.3-50.6) among those with recent IDU and needle/syringe sharing. In adjusted analysis, recent IDU with needle/syringe sharing was associated with increased reinfection risk (adjusted hazard ratio [aHR], 4.74 [95% CI: 1.33-16.80]; P = .016) and longer HCV testing interval with decreased risk (ie, chance of detection; aHR, 0.41 per each month increase [95% CI: .26-.64]; P < .001)., Conclusions: A high rate of HCV reinfection was observed within prison. Posttreatment surveillance and retreatment are -essential to limit the impact of reinfection. High-coverage OAT and NSPs should be considered within prisons., Clinical Trials Registration: NCT02064049., Competing Interests: Potential conflicts of interest. A. R. L. and G. J. D. were supported by NHMRC Practitioner Fellowships. J. G. was supported by an NHMRC Investigator Grant. E. C. is supported by a postdoctoral fellowship from the Canadian Network on Hepatitis C. P. V. acknowledges support from the US National Institute on Drug Abuse (NIDA; grant numbers R01AI147490, R01DA033679, R01DA037773, R21DA046809, and R01DA047952); the National Institute for Health Research (NIHR) Health Protection Research Unit in Evaluation of Interventions and Behavioral Science at the University of Bristol; and the NIHR-funded EPIToPe project. N. K. M. acknowledges support from the US National Institute of Allergy and Infectious Diseases and NIDA (grant number R01AI147490), and the University of California, San Diego Center for AIDS Research, a program funded by the US National Institutes of Health (grant number P30 AI036214). C. T. reports research funds, unrelated to this project, paid to the institution from Merck, and speaker’s fees from AbbVie and Gilead. G. J. D. reports research grants outside the submitted work from AbbVie, Gilead Sciences, and Merck. G. V. M. reports research grants from AbbVie and Gilead, outside the submitted work, and payment or honoraria from Janssen (speaker’s bureau) and AstraZeneca (advisory board). J. G. reports grants or contracts outside the submitted work from AbbVie, Camurus, Cepheid, Hologic, Indivior, and Merck and payment or honoraria from AbbVie, Cepheid, Gilead Sciences, and Merck. N. K. M. reports unrestricted research grants to the university unrelated to this research from Gilead and Merck. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: People who inject drugs are at greater risk of hepatitis C virus (HCV) infection and hospitalization, yet admissions are not utilized for HCV treatment initiation. We aimed to assess the extent to which people with HCV notification, including those with evidence of recent drug dependence, are hospitalized while eligible for direct-acting antiviral (DAA) therapy, and treatment uptake according to hospitalization in the DAA era., Methods: We conducted a longitudinal, population-based cohort study of people living with HCV in the DAA era (March 2016-December 2018) through analysis of linked databases in New South Wales, Australia. Kaplan-Meier estimates were used to report HCV treatment uptake by frequency, length, and cause-specific hospitalization., Results: Among 57 467 people, 14 938 (26%) had evidence of recent drug dependence, 50% (n = 7506) of whom were hospitalized while DAA eligible. Incidence of selected cause-specific hospitalization was highest for mental health-related (15.84 per 100 person-years [PY]), drug-related (15.20 per 100 PY), and injection-related infectious disease (9.15 per 100 PY) hospitalizations, and lowest for alcohol use disorder (4.58 per 100 PY) and liver-related (3.13 per 100 PY). In total, 65% (n = 4898) of those who were hospitalized had been admitted ≥2 times, and 46% (n = 3437) were hospitalized ≥7 days. By the end of 2018, DAA therapy was lowest for those hospitalized ≥2 times, for ≥7 days, and those whose first admission was for injection-related infectious disease, mental health disorders, and drug-related complications., Conclusions: Among people who have evidence of recent drug dependence, frequent hospitalization-particularly mental health, drug, and alcohol admissions-presents an opportunity for engagement in HCV care., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Evaluating progress towards hepatitis C virus (HCV) elimination is critical. This study estimated prevalence of current HCV infection and HCV treatment uptake among people who inject drugs (PWID) in Australia., Methods: The Enhancing Treatment of Hepatitis C in Opioid Substitution Settings Engage is an observational study of PWID attending drug treatment clinics and needle and syringe programs (NSPs). Participants completed a questionnaire including self-reported treatment history and underwent point-of-care HCV RNA testing (Xpert HCV Viral Load Fingerstick; Cepheid)., Results: Between May 2018 and September 2019, 1443 participants were enrolled (64% injected drugs in the last month, 74% receiving opioid agonist therapy [OAT]). HCV infection status was uninfected (28%), spontaneous clearance (16%), treatment-induced clearance (32%), and current infection (24%). Current HCV was more likely among people who were homeless (adjusted odds ratio, 1.47; 95% confidence interval, 1.00-2.16), incarcerated in the previous year (2.04; 1.38-3.02), and those injecting drugs daily or more (2.26; 1.43-2.42). Among those with previous chronic or current HCV, 66% (n = 520/788) reported HCV treatment. In adjusted analysis, HCV treatment was lower among females (.68; .48-.95), participants who were homeless (.59; .38-.96), and those injecting daily or more (.51; .31-.89). People aged ≥45 years (1.46; 1.06-2.01) and people receiving OAT (2.62; 1.52-4.51) were more likely to report HCV treatment., Conclusions: Unrestricted direct-acting antiviral therapy access in Australia has yielded high treatment uptake among PWID attending drug treatment and NSPs, with a marked decline in HCV prevalence. To achieve elimination, PWID with greater marginalization may require additional support and tailored strategies to enhance treatment., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: People who inject drugs (PWID) experience barriers to accessing testing and treatment for hepatitis C virus (HCV) infection. Opioid agonist therapy (OAT) may provide an opportunity to improve access to HCV care. This systematic review assessed the association of OAT and HCV testing, treatment, and treatment outcomes among PWID., Methods: Bibliographic databases and conference presentations were searched for studies that assessed the association between OAT and HCV testing, treatment, and treatment outcomes (direct-acting antiviral [DAA] therapy only) among PWID (in the past year). Meta-analysis was used to pool estimates., Results: Of 9877 articles identified, 22 studies conducted in Australia, Europe, North America, and Thailand were eligible and included. Risk of bias was serious in 21 studies and moderate in 1 study. Current/recent OAT was associated with an increased odds of recent HCV antibody testing (4 studies; odds ratio (OR), 1.80; 95% confidence interval [CI], 1.36-2.39), HCV RNA testing among those who were HCV antibody-positive (2 studies; OR, 1.83; 95% CI, 1.27-2.62), and DAA treatment uptake among those who were HCV RNA-positive (7 studies; OR, 1.53; 95% CI, 1.07-2.20). There was insufficient evidence of an association between OAT and treatment completion (9 studies) or sustained virologic response following DAA therapy (9 studies)., Conclusions: OAT can increase linkage to HCV care, including uptake of HCV testing and treatment among PWID. This supports the scale-up of OAT as part of strategies to enhance HCV treatment to further HCV elimination efforts., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: The aim of this analysis was to calculate the incidence of hepatitis C virus (HCV) reinfection and associated factors among 2 clinical trials of HCV direct-acting antiviral treatment in people with recent injecting drug use or currently receiving opioid agonist therapy (OAT)., Methods: Participants who achieved an end-of-treatment response in 2 clinical trials of people with recent injecting drug use or currently receiving OAT (SIMPLIFY and D3FEAT) enrolled between March 2016 and February 2017 in 8 countries were assessed for HCV reinfection, confirmed by viral sequencing. Incidence was calculated using person-time of observation and associated factors were assessed using Cox proportional hazard models., Results: Seventy-three percent of the population at risk of reinfection (n = 177; median age, 48 years; 73% male) reported ongoing injecting drug use. Total follow-up time at risk was 254 person-years (median, 1.8 years; range, 0.2-2.8 years). Eight cases of reinfection were confirmed for an incidence of 3.1/100 person-years (95% confidence interval [CI], 1.6-6.3) overall and 17.9/100 person-years (95% CI, 5.8-55.6) among those who reported sharing needles/syringes. Younger age and needle/syringe sharing were associated with HCV reinfection., Conclusions: These data demonstrate the need for ongoing monitoring and improved strategies to prevent HCV reinfection following successful treatment among people with ongoing injecting drug use to achieve HCV elimination., Clinical Trials Registration: NCT02336139 and NCT02498015., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

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., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: In many settings, recent or prior injection drug use remains a barrier to accessing direct-acting antiviral treatment (DAA) for hepatitis C virus (HCV) infection. We examined patterns of drug and alcohol use and injection equipment sharing among people with recent injecting drug use or receiving opioid agonist treatment (OAT) during and following DAA-based treatment., Methods: SIMPLIFY and D3FEAT are phase 4 trials evaluating the efficacy of DAA among people with past 6-month injecting drug use or receiving OAT through a network of 25 international sites. Enrolled in 2016-2017, participants received sofosbuvir/velpatasvir (SIMPLIFY) or paritaprevir/ritonavir/dasabuvir/ombitasvir ± ribavirin (D3FEAT) for 12 weeks and completed behavioral questionnaires before, during, and up to 2 years posttreatment. The impact of time in HCV treatment and follow-up on longitudinally measured longitudinally measured behaviors was estimated using generalized estimating equations., Results: At screening, of 190 participants (mean age, 47 years; 74% male), 62% reported any past-month injecting 16% past-month injection equipment sharing, and 61% current OAT. Median alcohol use was 2 (Alcohol Use Disorders Identification Test-Consumption; range, 1-12). During follow-up, opioid injecting (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.92-0.99) and sharing (OR, 0.87; 95% CI, 0.80-0.94) decreased, whereas no significant changes were observed for stimulant injecting (OR, 0.98; 95% CI, 0.94-1.02) or alcohol use (OR, 0.99; 95% CI, 0.95-1.04)., Conclusions: Injecting drug use and risk behaviors remained stable or decreased following DAA-based HCV treatment. Findings further support expanding HCV treatment to all, irrespective of injection drug use., Clinical Trials Registration: SIMPLIFY, NCT02336139; D3FEAT, NCT02498015., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: While opioid agonist therapy (OAT) reduces the risk of hepatitis C virus (HCV) acquisition among people who inject drugs (PWID), protective effects may be attenuated in females. We used pooled data from an international collaboration of prospective cohorts to assess sex disparities in HCV incidence among PWID exposed to OAT., Methods: Independent predictors of HCV infection were identified using Cox regression models with random effects after accounting for the clustering effect of study sites. Unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) are presented in sex-specific analyses., Results: Among 701 participants exposed to OAT, HCV incidence was 16.5/100 person-years of observation (PYO) (95% CI, 13.1-20.7) in females and 7.6/100 PYO (95% CI, 6.0-9.5) in males (female:male adjusted HR [aHR], 1.80 [95% CI, 1.37-2.22]; P < .001). Factors associated with HCV acquisition among females exposed to OAT included nonwhite race (aHR, 1.79 [95% CI, 1.25-2.56]; P = .001), unstable housing (aHR, 4.00 [95% CI, 3.62-4.41]; P < .001), daily or more frequent injection (aHR, 1.45 [95% CI, 1.01-2.08]; P = .042), and receptive syringe sharing (aHR, 1.43 [95% CI, 1.33-1.53]; P < .001)., Conclusions: Female PWID exposed to OAT are twice as likely as their male counterparts to acquire HCV. While there is a need for better understanding of sex differences in immune function and opioid pharmacokinetic and pharmacodynamic parameters, structural and behavioral interventions that target women are required to bolster the efficacy of OAT in preventing HCV transmission., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Cascade-of-care (CoC) monitoring is an important component of the response to the global hepatitis C virus (HCV) epidemic. CoC metrics can be used to communicate, in simple terms, the extent to which national and subnational governments are advancing on key targets, and CoC findings can inform strategic decision-making regarding how to maximize the progression of individuals with HCV to diagnosis, treatment, and cure. The value of reporting would be enhanced if a standardized approach were used for generating CoCs. We have described the Consensus HCV CoC that we developed to address this need and have presented findings from Denmark, Norway, and Sweden, where it was piloted. We encourage the uptake of the Consensus HCV CoC as a global instrument for facilitating clear and consistent reporting via the World Health Organization (WHO) viral hepatitis monitoring platform and for ensuring accurate monitoring of progress toward WHO's 2030 hepatitis C elimination targets., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: The objective of this study was to assess differences in hepatitis C virus (HCV) incidence by sex in people who inject drugs (PWID), using a large international multicohort set of pooled biological and behavioral data from prospective observational studies of incident human immunodeficiency virus (HIV) and HCV infections in high-risk cohorts (the InC3 Collaborative)., Methods: HCV infection date was estimated based on a hierarchy of successive serological (anti-HCV), virological (HCV RNA), and clinical (symptoms and/or liver function tests) data. We used a Cox proportional hazards model to calculate the crude and adjusted female to male (F:M) hazard ratio (HR) for HCV incidence using biological sex as the main exposure., Results: A total of 1868 PWID were observed over 3994 person-years of observation (PYO). Unadjusted F:M HR was 1.38 (95% confidence interval [CI], 1.15-1.65) and remained significant after adjusting for behavioral and demographic risk factors (1.39 [95% CI, 1.12-1.72]). Although syringe and equipment sharing were associated with the highest HCV incidence rate in women (41.62 and 36.83 PYO, respectively), we found no sex differences attributed to these risk factors., Conclusions: Our findings indicate that women who inject drugs may be at greater risk of HCV acquisition than men, independent of demographic characteristics and risk behaviors. Multiple factors, including biological (hormonal), social network, and differential access to prevention services, may contribute to increased HCV susceptibility in women who inject drugs., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: We determined temporal trends (1985-2011) in hepatitis C virus (HCV) incidence and associated behavioral exposures for people who inject drugs (PWID) from the United States (Boston, Baltimore, and San Francisco), Canada (Montreal), the Netherlands (Amsterdam), and Australia (Sydney and Melbourne)., Methods: Using population-based cohort data from HCV-negative PWID, we calculated overall and within-city HCV incidence trends, HCV rates by study enrollment period (1985-2011), and temporal trends in exposure behaviors. Poisson regression models estimated trends in HCV incidence over calendar-time. Survival models identified risk factors for HCV incidence across cities and estimated independent effects of city and calendar period on HCV infection risk., Results: Among 1391 initially HCV-negative participants followed prospectively (1644.5 person-years of observation [PYO]), 371 HCV incident infections resulted in an overall incidence of 22.6 per 100 PYO (95% confidence interval [CI], 20.4-25.0). Incidence was highest and remained elevated in Baltimore (32.6/100 PYO), San Francisco (24.7/100 PYO), and Montreal (23.5/100 PYO), lowest in Melbourne and Amsterdam (7.5/100 PYO and 13.1/100 PYO, respectively), and moderate (21.4/100 PYO) in Sydney. Higher rates of syringe and equipment sharing and lower prevalence of opioid agonist therapy were associated with HCV incidence in cities with the highest incidence. Risk for infection dropped by 18% for every 3-year increase in calendar-time (adjusted hazard ratio, 0.8 [95% CI, .8-.9]) in the multivariable model., Conclusions: Differences in prevention strategies and injecting contexts may explain the ongoing high HCV incidence in these North American cities and emphasize the need for scale-up of opioid agonist therapy and increased coverage of needle and syringe programs in North America., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.)

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., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background:  Interferon-based hepatitis C virus (HCV) therapy is safe and effective among people receiving opioid substitution therapy (OST), but treatment uptake remains low. Our aim was to evaluate the impact of OST and drug use during therapy on completion, adherence, sustained virologic response (SVR12), and safety of ledipasvir/sofosbuvir ± ribavirin., Methods:  The phase 3 ION studies evaluated a fixed-dose combination of ledipasvir/sofosbuvir ± ribavirin administered for 8, 12, or 24 weeks in patients with chronic HCV genotype 1. People with clinically significant drug use (prior 12 months) or noncannabinoids detected at screening by urine drug tests (not explained by prescriptions) were ineligible. Stored samples were available from ION-1 for retrospective testing for illicit drugs by enzyme-linked immunosorbent assay., Results:  Among 1952 patients enrolled in the ION studies, 4% (n = 70) were receiving OST. Among those receiving (n = 70) and not receiving OST (n = 1882), there was no difference in treatment completion (97% vs 98%; P = .40), ≥80% adherence (93% vs 92%; P = 1.00), SVR12 (94% vs 97%; P = .28), and serious adverse events (4% vs 3%; P = .43), respectively. Among participants in the ION-1 trial, 23% (n = 196) used illicit drugs during therapy (15% cannabinoids alone; 8% other illicit drugs ± cannabinoids). There was no difference in treatment completion, ≥80% adherence, SVR12, or serious AEs in those with no drug use during treatment compared with those who used cannabinoids and/or other illicit drugs. No cases of HCV reinfection were observed in the 24 weeks following treatment., Conclusions:  OST and drug use during HCV therapy did not impact treatment completion, adherence, SVR12, or safety., Clinical Trials Registration:  ION-1 (NCT01701401); ION-2 (NCT01768286); and ION-3 (NCT01851330)., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

The demonstration that antiretroviral treatment is effective for the prevention of human immunodeficiency virus (HIV) transmission has important implications for HCV prevention. HCV therapeutic development is advancing rapidly, with effective, simplified regimens available in the near future. In contrast to HIV, HCV treatment is both curative and circumscribed in duration-2 features that hold great promise for the potential effectiveness of HCV treatment as prevention, particularly among PWID. Mathematical modeling studies have suggested that modest increases in HCV treatment uptake could lead to substantial reductions in HCV prevalence. This Viewpoint focuses on issues that are important to consider when discussing the feasibility and future requirements of HCV treatment as prevention among PWID. This includes a need to address low rates of HCV screening and treatment, a limited HCV treatment infrastructure, the cost of therapy, and the balance of health priorities at the population and individual levels.

Background: Access to hepatitis C virus (HCV) treatment remains extremely limited among people who inject drugs (PWID). HCV assessment and treatment was evaluated through an innovative model for the provision of HCV care among PWID with chronic HCV infection., Methods: Enhancing Treatment for Hepatitis C in Opioid Substitution Settings (ETHOS) was a prospective observational cohort. Recruitment was through 5 opioid substitution treatment (OST) clinics, 2 community health centers, and 1 Aboriginal community controlled health organization in New South Wales, Australia., Results: Among 387 enrolled participants, mean age was 41 years, 71% were male, and 15% were of Aboriginal ethnicity. Specialist assessment was undertaken in 191 (49%) participants, and 84 (22%) commenced interferon-based treatment. In adjusted analysis, HCV specialist assessment was associated with non-Aboriginal ethnicity (adjusted odds ratio [AOR], 4.02; 95% confidence interval [CI], 2.05-7.90), no recent benzodiazepine use (AOR, 2.06; 95% CI, 1.31-3.24), and non-1 HCV genotype (AOR, 2.13; 95% CI, 1.32-3.43). In adjusted analysis, HCV treatment was associated with non-Aboriginal ethnicity (AOR, 4.59; 95% CI, 1.49-14.12), living with the support of family and/or friends (AOR, 2.15; 95% CI, 1.25-3.71), never receiving OST (AOR, 4.40; 95% CI, 2.27-8.54), no recent methamphetamine use (AOR, 2.26; 95% CI, 1.12-4.57), and non-1 HCV genotype (AOR, 3.07; 95% CI, 1.67-5.64)., Conclusions: HCV treatment uptake was relatively high among this highly marginalized population of PWID. Potentially modifiable factors associated with treatment include drug use and social support.

In the developed world, the majority of new and existing hepatitis C virus (HCV) infections occur among people who inject drugs (PWID). The burden of HCV-related liver disease in this group is increasing, but treatment uptake among PWID remains low. Among PWID, there are a number of barriers to care that should be considered and systematically addressed, but these barriers should not exclude PWID from HCV treatment. Furthermore, it has been clearly demonstrated that HCV treatment is safe and effective across a broad range of multidisciplinary healthcare settings. Given the burden of HCV-related disease among PWID, strategies to enhance HCV assessment and treatment in this group are urgently needed. These recommendations demonstrate that treatment among PWID is feasible and provides a framework for HCV assessment, management, and treatment. Further research is needed to evaluate strategies to enhance assessment, adherence, and SVR among PWID, particularly as new treatments for HCV infection become available.

Background: This study investigated the efficacy and safety of directly observed pegylated interferon (peg-IFN) alfa-2a plus self-administered ribavirin (RBV) for the treatment of hepatitis C virus (HCV) among people with active drug use., Methods: A randomized, open-label, parallel group trial of immediate vs delayed treatment with peg-IFN alfa-2a plus RBV in participants with recent injection drug and/or crack cocaine use (prior 3 months). The primary end point was sustained virologic response (SVR)., Results: Sixty-six participants were randomized (immediate treatment, n = 48; delayed treatment, n = 18). Loss to follow-up was comparable among those randomized to immediate and delayed treatment (23% vs 33%, P = .389). In a post hoc intent-to-treat analysis of all randomized individuals, the SVR was 65% (95% confidence interval [CI], 49%-78%; 31/48) in those randomized to immediate treatment as compared to 39% (95% CI, 17%-64%; 7/18) in those randomized to delayed treatment (P = .060). Among those who received delayed treatment (12/18), SVR was 58% (7/12). Among 60 participants who received at least 1 dose of study medication, SVR was 63% (95% CI, 50%-75%, n = 38). Recent drug use at baseline (past month) did not impact completion or SVR. Discontinuation due to adverse events occurred in 7%. The HCV reinfection rate was 2.8 per 100 person-years (95% CI, 0.0-14.5 person-years) with 1 reinfection observed among 23 remaining in follow-up post-SVR (median, 1.8 years; range, 0.5-1.8 years)., Conclusions: Among people actively using drugs treated with directly observed peg-IFN alfa-2a plus self-administered RBV, SVR is comparable to that seen in clinical trials of non-drug users, and the rate of HCV reinfection is low.

Background: Although guidelines recommend that people who inject drugs (PWID) should not be excluded from hepatitis C (HCV) treatment, some services remain reluctant to treat PWID. The aim of this review was to investigate sustained virologic response (SVR), adherence, discontinuation, and HCV reinfection among PWID., Methods: A search of Medline, Embase, and Cochrane databases (between 2002 and January 2012) was conducted for primary articles/conference abstracts examining HCV treatment outcomes in PWID. Meta-analysis was used to obtain pooled estimates of SVR, adherence, discontinuation, and HCV reinfection., Results: Ten primary articles and 1 conference abstract met the inclusion criteria. Across 6 studies (comprising 314 drug users, of whom 141 [45%] were PWID), pooled SVR was 56% (95% confidence interval [CI], 50%-61%) for all genotypes, 37% (95% CI, 26%-48%) for genotypes 1/4, and 67% (95% CI, 56%-78%) for genotypes 2/3. Pooled 80/80/80 adherence was 82% (95% CI, 74%-89%) across 2 studies, and pooled treatment discontinuation was 22% (95% CI, 16%-27%) across 4 studies. Across 5 studies (comprising 131 drug users) examining reinfection, pooled risk was 2.4 (95% CI, .9-6.1) per 100 person-years., Conclusions: HCV treatment outcomes are acceptable in PWID, supporting treatment guidelines. The pooled estimate of HCV reinfection risk was low, but there was considerable uncertainty around this estimate. Further studies on the risk of reinfection are needed to assess the long-term effectiveness of HCV treatment in PWID.

Background: Injecting drug users remain the population at greatest risk of acquiring hepatitis C virus (HCV) infection, although a recent increase in cases of sexually transmitted HCV infection has been observed among human immunodeficiency virus (HIV)-infected individuals. The extent to which these separate epidemics overlap is unknown., Methods: The Australian Trial in Acute Hepatitis C (ATAHC) enrolled 163 individuals (29% of whom were HIV infected) with recent HCV infection. E1/HVR1 sequences were used to construct phylogenetic trees demonstrating monophyletic clusters or pairs, and viral epidemic history and phylogeography were assessed using molecular clock analysis. Individual clusters were characterized by clinical and demographic characteristics., Results: Transmission through injection drug use occurred for 73% of subjects, with sexual transmission occurring for 18% (92% of whom were HIV infected). Among 112 individuals with available E1/HVR1 sequences, 23 (20%) were infected with a strain of HCV identical to that of another subject, comprising 4 homologous clusters and 3 monophyletic pairs, the majority of which (78%) were HIV infected. Clusters contained individuals with both injection drug use-related and sex-related acquisition, and in all clusters (except for 1 female HIV-uninfected pair), individuals identified as men who have sex with men, irrespective of HIV status., Conclusions: This large unique study of HIV-infected and HIV-uninfected individuals with recently acquired HCV infection demonstrates that clustering is common in the HIV-infected population and that it occurred almost invariably among men who have sex with men, irrespective of the actual mode of acquisition. These findings suggest the coexistence of both injection drug use and sexual risk behaviors for individuals in the same social networks and have implications for the development of public health messages. Clinical trial registration. NCT00192569.

The treatment of injection drug users (IDUs) coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) presents multiple challenges, many of which could be addressed by the development of directly observed therapy programs. This is made all the more feasible by the validation of once-daily treatment regimens for HIV. We have demonstrated that virological suppression can be achieved and maintained in as many as 80% of active IDUs who have received highly active antiretroviral therapy for 48 months. This approach has now been validated in first- and second-line therapy, as well as for the treatment of bacterial infections in this population, achieving therapeutic results similar to those reported in the general population. The model is now being applied to the treatment of HCV infection, focusing on patients with infection due to HCV genotype 2 or 3, in whom the likelihood of response may exceed 80%. Our ultimate goal is to ensure that, even in treating IDUs in the inner city, no patient is left behind.