Direct-acting Antiviral Medications Research Articles

The Association between Urinary Alcohol Metabolites on Hepatitis C Treatment and Response

Background: Direct-acting antiviral (DAA) medications for the treatment of chronic hepatitis C virus (HCV) infection has achieved higher rates of sustained virologic response (SVR) with shorter treatment durations and no alcohol abstinence prerequisite. Previous therapies required alcohol abstinence for at least 6 months. Methods: Our retrospective cohort study in Veterans with chronic HCV infection presenting for care at the Joseph Maxwell Cleland Atlanta VA medical center (AVAMC) between 1/1/2015 – 11/29/2017 examined the relationship between alcohol use, DAA initiation, and SVR. Results: The cohort included 1763 people that were mostly males (97%) with a mean age of 63 years and 70% Black. In multivariate analysis, the odds of receiving DAA were 0.7 (95% CI: 0.674, 0.9; p=0.0013) in those with “detectable” alcohol metabolites compared with those who had “undetectable” alcohol metabolites. The odds of achieving SVR were 0.7 (95% CI: 0.5, 1.0; p=0.0525) in those with “detectable” alcohol metabolites. Overall, 86% of patients who received DAA therapy achieved SVR. Conclusions: Alcohol use categorized using urine alcohol metabolite testing, during the study period was associated with a significantly lower odds of receiving DAA therapy but had no statistical significance on the odds of achieving SVR. While patients with chronic hepatitis C should be counseled on the risks of alcohol use, it is not associated with lower likelihood of achieving SVR and should not preclude the initiation of DAA therapy

Pilot study of a community pharmacist led program to treat hepatitis C virus among people who inject drugs

BackgroundPeople who inject drugs (PWID) are a key population for treatment with direct-acting antiviral medications (DAAs) to eliminate hepatitis C virus (HCV). We developed a Pharmacist, Physician, and Patient Navigator Collaborative Care Model (PPP-CCM) for delivery of HCV treatment; this study describes clinical outcomes related to HCV treatment (initial evaluation, treatment initiation, completion, and cure), as well as patient satisfaction. MethodsWe conducted a single-arm prospective pilot study of adult PWID living with HCV. Participants completed baseline and six-month follow-up surveys, and treatment and outcomes were abstracted from electronic health records. Primary outcome was linkage to pharmacist for HCV evaluation; secondary outcomes included DAA initiation, completion, and cure, as well as patient-reported satisfaction. ResultsOf the 40 PWID enrolled, mean age was 43.6 years, 12 (30 %) were female, 20 (50 %) were non-white, and 15 (38 %) were unhoused. Thirty-eight (95 %) were successfully linked to the pharmacist for initial evaluation. Of those, 21/38 (55 %) initiated DAAs, and 16/21 (76 %) completed treatment. Among those completing treatment who had viral load data to document whether they achieved “sustained virologic response", i.e. cure, 10/11 (91 %) were found to be cured. There was high satisfaction with 100 % responding “agree or strongly agree” that they had a positive experience with the pharmacist. ConclusionNearly all participants in this pilot were successfully linked to the pharmacist for evaluation, and more than half were started on DAAs; results provide preliminary evidence of feasibility of pharmacist-led models of HCV treatment for PWID. Clinicaltrials.gov registration numberNCT04698629.

Safety and efficacy of treatment for chronic hepatitis C during pregnancy: A prospective observational study in Srinagar, India.

In India, the estimated prevalence of antenatal HCV infection is 0.3%-2.8%, and the rate of mother-to-child transmission has been estimated at 5%-15%. HCV treatment during pregnancy could reduce maternal complications from HCV infection, prevent transmission to the infant, and reduce HCV infection overall in women of childbearing age. However, there are limited studies of HCV treatment with direct-acting antiviral medications during pregnancy, and therefore, direct-acting antivirals are not commonly used for treatment during pregnancy. We describe our institutional experience in this prospective observational study over 3 years at the Sher-I-Kashmir Institute of Medical Sciences, Srinagar, India. Patients with chronic hepatitis C in pregnancy were enrolled and treated with ledipasvir and sofosbuvir after the first trimester. Primary end points were sustained virologic response at 12 weeks, adverse drug reactions, and congenital malformation of the infant. The secondary end point was the transmission of HCV infection to the infant. We enrolled 26 patients in our study. The mean age was 28 years (range of 21-36y). All patients were noncirrhotic and treatment-naive. The mean HCV RNA before treatment was 9.2 ×10^5IU/ml. Among the enrolled patients, 19 (73%) were genotype 3, 5 (19%) were genotype 1, and 2 (8%) were genotype 4. All patients achieved sustained virologic response at 12 weeks. Some patients reported nausea (27%), headache (27%), and fatigue (16%). All patients had institutional delivery, and no infant was found to have congenital malformations. No child had detectable HCV RNA at 6 months of age. To our knowledge, we here report results from the largest cohort of pregnant women treated for HCV infection globally. Ledipasvir and sofosbuvir were well tolerated and highly effective for both HCV cure in the mother and elimination of mother-to-child transmission. No congenital abnormalities were detected in our cohort. Elimination of mother-to-child transmission is urgently needed, and this study has shown that treatment of HCV during pregnancy may be a pragmatic approach for the greater benefit of both mother and the newborn.

Characterizing Persons With HIV/HCV Coinfection Who Remain Untreated for Hepatitis C at Four HIV Clinics in Connecticut (CT): Role of Multiple Overlapping Barriers at the Individual and Clinic System Levels.

Introduction. Direct-acting antiviral medications have made hepatitis C virus (HCV) cure possible for >95% of persons with chronic HCV infection, including those coinfected with HIV. Achieving strategic HCV elimination targets requires an understanding of system, provider, and patient-level barriers to treatment. We explored such barriers among persons with HIV/HCV coinfection who remained untreated for HCV. Methods. Among four primary care HIV clinics in CT with high rates of HCV cure, 25 patients with HIV/HCV coinfection were eligible (no HCV treatment as of March 31, 2021). We conducted retrospective chart reviews of demographics, clinical practice patterns, patient-specific issues such as housing, transportation, food security, and presence of mental health and substance use problems. Results. Among untreated patients, 13 (51%) were female; 17 (68%) were Black; median age was 62 years old. The majority (84%) had injecting drug use (IDU) as HIV transmission risk factor; 14 (56%) were prescribed medication-assisted treatment. Median time since HIV and HCV diagnosis was 25 and 19 years, respectively. Clinic-level barriers were noted in 19 (76%) and included lack of evaluation, treatment not recommended or implemented. Concomitant structural barriers included unstable housing for 11 (44%) and lack of transportation for eight (32%). Most patients had history of illicit substance use (84%) and mental health issues (68%). Many (76%) had multiple potential barriers. Conclusions. Multiple overlapping barriers spanning clinic and patient level domains including social determinants of health were the norm in persons with long-standing HIV/HCV coinfection who have not received HCV treatment. Interventions will require innovative, multi-disciplinary and personalized approaches.

A Video-Observed Treatment Strategy to Improve Adherence to Treatment Among Persons Who Inject Drugs Infected With Hepatitis C Virus: Qualitative Study of Stakeholder Perceptions and Experiences.

Direct-acting antiviral medications have the potential to eliminate the hepatitis C virus (HCV) epidemic among people who inject drugs; yet, suboptimal adherence remains a barrier. Directly observed treatment (DOT), an effective strategy for optimizing adherence, has been frequently implemented in opioid treatment programs but less commonly in community health settings due to the heavy burden of daily visits. An alternative is video-observed therapy (VOT), which uses mobile health technology to monitor adherence. VOT has not been widely studied among people who inject drugs with HCV. This qualitative study, part of a larger implementation evaluation, investigates stakeholder perceptions and experiences with VOT in Project HERO (Hepatitis C Real Outcomes), a multisite pragmatic trial testing treatment delivery models for people who inject drugs with HCV. Our goal was to understand the potential barriers and facilitators to the implementation of the VOT technology. Qualitative interviews were conducted with 27 Project HERO study staff and 7 patients. Interviews focused on perceptions and experiences with the VOT app and barriers and facilitators to implementation. Team meeting minutes over the first 2 years of the project were transcribed. A coding system was developed and applied to the data. We summarized thematic data and compared participant perceptions to generate a close understanding of the data. Frequent barriers to VOT included mechanical failure, stolen or lost phones, and a steep learning curve for participants and study staff. In sites with older and less technically skilled participants, staff found it difficult to implement the VOT app. Research staff found that the routine monitoring of app use led to closer engagement with participants. This was both a benefit and a potential threat to the validity of this pragmatic trial. Patient participants reported mixed experiences. VOT may be a useful alternative to DOT for some patients, but it may not be feasible for all. Significant staff involvement may be required.

Implementing a Surveillance-Based Approach to Create a Statewide Viral Clearance Cascade for Hepatitis C Among People With HIV and HCV Coinfection in Connecticut.

Highly effective direct-acting antiviral medications have made it feasible to achieve elimination of hepatis C virus (HCV), including for people with HIV and HCV coinfection. The Centers for Disease Control and Prevention offers guidance for a laboratory surveillance-based HCV viral clearance cascade, which allows public health departments to track the outcomes of people with HCV based on the following steps: ever infected, virally tested, initial infection, and cured or cleared. We examined the feasibility of this approach among people with HIV and HCV coinfection in Connecticut. We matched an HIV surveillance database, which included cases from the enhanced HIV/AIDS Reporting System as of December 31, 2019, and the HCV surveillance database, the Connecticut Electronic Disease Surveillance System, to define a cohort of coinfected people. We used HCV laboratory results obtained from January 1, 2016, through August 3, 2020, to determine HCV status. Of 1361 people who were ever infected with HCV as of December 31, 2019, 1256 (92.3%) received HCV viral testing, 865 of 1256 people tested (68.9%) were HCV infected, and 336 of 865 infected people (38.8%) were cleared or cured. People who had undetectable HIV viral loads at most recent HIV test (<200 copies/mL) were more likely than those with detectable HIV viral loads to achieve HCV cure (P = .02). A surveillance-based approach that includes data based on the Centers for Disease Control and Prevention HCV viral clearance cascade is feasible to implement, can help track population-level outcomes longitudinally, and can help identify gaps to inform HCV elimination strategies.

Training Providers of People Who Use Drugs to Offer Hepatitis C Treatment: A Washington State Initiative.

To address hepatitis C infection (HCV) treatment gaps among people who use drugs (PWUD), a statewide initiative trained buprenorphine waiver trainers to offer an optional HCV treatment module to waiver trainees. Five of twelve trained buprenorphine trainers went on to conduct HCV sessions at waiver trainings, reaching 57 trainees. Word-of-mouth led to multiple additional presentations by the project team, suggesting an unmet need for more education about treating HCV among PWUD. A post-session survey suggested that participant views on the importance of treating HCV among PWUD changed and that almost all felt confident to treat uncomplicated HCV. While limitations of this evaluation include that no baseline survey was conducted and that the survey response rate was low, findings suggest that among providers who care for PWUD, limited training may be adequate to change views about treating HCV. Future research is needed to explore models of care that will support providers to prescribe lifesaving direct-acting antiviral medications to PWUD with HCV.

The association of donor hepatitis C virus infection with 3-year kidney transplant outcomes in the era of direct-acting antiviral medications

To determine the effect of donor hepatitis C virus (HCV) infection on kidney transplant (KT) outcomes in the era of direct-acting antiviral (DAA) medications, we examined 68,087 HCV-negative KT recipients from a deceased donor between March 2015 and May 2021. A Cox regression analysis was used to estimate adjusted hazard ratios (aHRs) of KT failure, incorporating inverse probability of treatment weighting to control for patient selection to receive an HCV-positive kidney (either nucleic acid amplification test positive [NAT+, n = 2331] or antibody positive (Ab+)/NAT− [n = 1826]) based on recipient characteristics. Compared with kidney from HCV-negative donors, those from Ab+/NAT− (aHR = 0.91; 95% confidence interval [CI], 0.75-1.10) and HCV NAT+ (aHR = 0.89; 95% CI, 0.73-1.08) donors were not associated with an increased risk of KT failure over 3 years after transplant. Moreover, HCV NAT+ kidneys were associated with a higher 1-year estimated glomerular filtration (63.0 vs 61.0 mL/min/1.73 m2, P = .007) and lower risk of delayed graft function (aOR = 0.76; 95% CI, 0.68-0.84) compared with HCV-negative kidneys. Our findings suggest that donor HCV positivity is not associated with an elevated risk of graft failure. The inclusion of donor HCV status in the Kidney Donor Risk Index may no longer be appropriate in contemporary practice.

Reevaluating Liver Donor Risk in the Era of Improved Hepatitis C Virus Treatment

This cohort study examines the risk of graft failure associated with donors with hepatitis C virus (HCV) infection before and after the introduction of direct-acting antiviral medications.

Post-crisis imaginaries in the time of direct-acting antiviral hepatitis C treatment

Until the recent introduction of direct-acting antiviral (DAA) medications, the only available hepatitis C treatments were lengthy and onerous interferon-based therapies, with relatively weak success rates. While experiences of interferon-based treatment have been well documented, there is a need to better understand how the experiences of the ‘old’ treatments shape contemporary treatment experiences. This article uses the concept of ‘post-crisis’ developed in critical scholarship on HIV/AIDS, and recent theorisations of ‘curative time’, to explore the relationship between contemporary treatment experiences and the legacies of interferon-based therapies. In mobilising these concepts, we trouble linear temporal logics that take for granted distinctions between the past and present, old and new, and cure and post-cure, and draw attention to the fluidity of time and the overlapping co-constitutive terrains of meaning that shape treatment experiences. Drawing on 50 interviews with people affected by hepatitis C, we argue that the curative imaginary of DAA treatments – that is, the temporal framing applied to hepatitis C in which cure is expected and assumed – is shaped by the logic of crisis. Here, knowledge of and the possibilities for the new treatments and living with hepatitis C remain tethered to crisis accounts of interferon. Unlike HIV/AIDS, in which the disease itself was figured as crisis, many participants described interferon-based treatments as the crisis: as worse than living with hepatitis C. While the new treatments were widely described as simple and easy, we argue that treatment is not so straightforward and that the crisis/post-crisis relation is central to this complexity . We conclude by considering the significance of these post-crisis enactments for understanding the recent plateauing of DAA treatment uptake, and reflect on how post-crisis futures of hepatitis C ‘cure’ need to address the ongoing constitutive effects of interferon-based treatments.

Innovative Approaches to Engaging Homeless and Marginally Housed Patients in Care: a Case Study of Hepatitis C.

Homeless and marginally housed (HAMH) individuals experience significant health disparities compared to housed counterparts, including higher hepatitis C virus (HCV) rates. New direct-acting antiviral (DAA) medications dramatically increased screening and treatment rates for HCV overall, but inequities persist for HAMH populations. This study examines the range of policies, practices, adaptations, and innovations implemented by Veteran Affairs Medical Centers (VAMCs) in response to Veterans Health Administration (VHA)'s 2016 HCV funding allocation to expand provision of HCV care. Ethnographic site visits to six US VAMCs varying in size, location, and availability of Homeless Patient-Aligned Care Teams. Semi-structured qualitative interviews informed by the HCV care continuum were conducted with providers, staff, and HAMH patients to elicit experiences providing and receiving HCV care. Semi-structured field note templates captured clinical care observations. Interview and observation data were analyzed to identify cross-cutting themes and strategies supporting tailored HCV care for HAMH patients. Fifty-six providers and staff working in HCV and/or homelessness care (e.g., infectious disease providers, primary care providers, social workers). Twenty-five patients with varying homeless experiences, including currently, formerly, or at risk of homelessness (n=20) and stably housed (n=5). All sites experienced challenges with continued engagement of HAMH individuals in HCV care, which led to the implementation of targeted care strategies to better meet their needs. Across sites, we identified 35 unique strategies used to find, engage, and retain HAMH individuals in HCV care. Despite highly effective, widely available HCV treatments, HAMH individuals continue to experience challenges accessing HCV care. VHA's 2016 HCV funding allocation resulted in rapid adoption of strategies to engage and retain vulnerable patients in HCV treatment. The strategies identified here can help healthcare institutions tailor and target approaches to provide sustainable, high-quality, equitable care to HAMH individuals living with HCV and other chronic illnesses.

Hepatocellular Carcinoma Risk Declines but Remains High Enough for Screening in the First 7 Years After Hepatitis C Virus Cure With Direct-Acting Antivirals in Patients With Cirrhosis or High Fibrosis-4 Score

Hepatitis C virus (HCV) eradication by direct-acting antiviral (DAA) medications has been found to reduce hepatocellular carcinoma (HCC) risk, but a substantial risk persists in patients with cirrhosis and those with Fibrosis-4 (FIB-4) score ≥3.25. 1 Ioannou G.N. et al. Gastroenterology. 2019; 157: 1264-1278.e4 Abstract Full Text Full Text PDF PubMed Scopus (152) Google Scholar ,2 Ioannou G.N. et al. J Hepatol. 2018; 68: 25-32 Abstract Full Text Full Text PDF Scopus (258) Google Scholar In a previous study, we found that, during the first 4 years after DAA-induced sustained virologic response (SVR), annual HCC incidence remained well above 2% in those with pretreatment cirrhosis and above 1% in those without cirrhosis but with pretreatment FIB-4 score ≥3.25. 1 Ioannou G.N. et al. Gastroenterology. 2019; 157: 1264-1278.e4 Abstract Full Text Full Text PDF PubMed Scopus (152) Google Scholar In that study, annual HCC risk declined during the first 4 years of follow-up, but the follow-up time was not long enough to determine whether HCC risk continues to decline to levels low enough that HCC screening may no longer be warranted. In this study, we extended the follow-up of this DAA-cured cohort up to 7 years to determine whether annual HCC risk, stratified by cirrhosis and FIB-4 categories, declines to levels low enough to preclude the requirement for HCC screening.

Kidney Transplantation From Hepatitis-C Viraemic Donors:Considerations for Practice in the United Kingdom.

Background: Donor hepatitis-C (HCV) infection has historically represented a barrier to kidney transplantation (KT). However, direct-acting antiviral (DAA) medications have revolutionised treatment of chronic HCV infection. Recent American studies have demonstrated that DAA regimes can be used safely peri-operatively in KT to mitigate HCV transmission risk. Methods: To formulate this narrative review, a comprehensive literature search was performed to analyse results of existing clinical trials examining KT from HCV-positive donors to HCV-negative recipients with peri-operative DAA regimes. Results: 13 studies were reviewed (11 single centre, four retrospective). Outcomes for 315 recipients were available across these studies. A sustained virological response at 12 weeks (SVR12) of 100% was achieved in 11 studies. One study employed an ultra-short DAA regime and achieved an SVR12 of 98%, while another achieved SVR12 of 96% due to treatment of a missed mixed genotype. Conclusion: HCV+ KT is safe and may allow increased utilisation of organs for transplantation from HCV+ donors, who often have other favourable characteristics for successful donation. Findings from US clinical trials can be applied to the United Kingdom transplant framework to improve organ utilisation as suggested by the NHSBT vision strategy “Organ Donation and Transplantation 2030: meeting the need”.

Characteristics of hepatitis C virus resistance in an international cohort after a decade of direct-acting antivirals

Background & AimsDirect-acting antiviral (DAA) regimens provide a cure in >95% of patients with chronic HCV infection. However, in some patients in whom therapy fails, resistance-associated substitutions (RASs) can develop, limiting retreatment options and risking onward resistant virus transmission. In this study, we evaluated RAS prevalence and distribution, including novel NS5A RASs and clinical factors associated with RAS selection, among patients who experienced DAA treatment failure.MethodsSHARED is an international consortium of clinicians and scientists studying HCV drug resistance. HCV sequence linked metadata from 3,355 patients were collected from 22 countries. NS3, NS5A, and NS5B RASs in virologic failures, including novel NS5A substitutions, were examined. Associations of clinical and demographic characteristics with RAS selection were investigated.ResultsThe frequency of RASs increased from its natural prevalence following DAA exposure: 37% to 60% in NS3, 29% to 80% in NS5A, 15% to 22% in NS5B for sofosbuvir, and 24% to 37% in NS5B for dasabuvir. Among 730 virologic failures, most were treated with first-generation DAAs, 94% had drug resistance in ≥1 DAA class: 31% single-class resistance, 42% dual-class resistance (predominantly against protease and NS5A inhibitors), and 21% triple-class resistance. Distinct patterns containing ≥2 highly resistant RASs were common. New potential NS5A RASs and adaptive changes were identified in genotypes 1a, 3, and 4. Following DAA failure, RAS selection was more frequent in older people with cirrhosis and those infected with genotypes 1b and 4.ConclusionsDrug resistance in HCV is frequent after DAA treatment failure. Previously unrecognized substitutions continue to emerge and remain uncharacterized.Lay summaryAlthough direct-acting antiviral medications effectively cure hepatitis C in most patients, sometimes treatment selects for resistant viruses, causing antiviral drugs to be either ineffective or only partially effective. Multidrug resistance is common in patients for whom DAA treatment fails. Older patients and patients with advanced liver diseases are more likely to select drug-resistant viruses. Collective efforts from international communities and governments are needed to develop an optimal approach to managing drug resistance and preventing the transmission of resistant viruses.

Medicaid Subscription-Based Payment Models and Implications for Access to Hepatitis C Medications

Hepatitis C virus (HCV) can be cured with direct-acting antiviral medications, but state Medicaid programs often restrict access to these lifesaving medications owing to their high costs. Subscription-based payment models (SBPMs), wherein states contract with a single manufacturer to supply prescriptions at a reduced price, may offer a solution that increases access. Whether SBPMs are associated with changes in HCV medication use is unknown. To estimate changes in Medicaid-covered HCV prescription fills after Louisiana and Washington implemented SBPMs on July 1, 2019. This cross-sectional study examined trends in prescription fills of Medicaid-covered direct-acting antiviral HCV medications in Louisiana and Washington after implementation of SBPMs. A synthetic control approach was used to compare changes in HCV prescription fills between states that did and did not implement SBPMs. The unit of analysis was state-quarter. Outpatient direct-acting antiviral HCV prescription fills from the Medicaid State Drug Utilization Data files were obtained from all 50 US states and the District of Columbia from January 1, 2017, to June 30, 2020. Implementation of SBPMs for Medicaid-covered direct-acting antiviral HCV medications. Direct-acting antiviral HCV prescriptions filled per 100 000 Medicaid enrollees. In the year preceding SBPM implementation, the mean (SD) rate of quarterly HCV prescription fills per 100 000 Medicaid enrollees was 43.1 (8.6) prescriptions in Louisiana and 50.1 (4.1) in Washington. After SBPM implementation, the mean (SD) rate of quarterly HCV prescription fills per 100 000 enrollees was 206.0 (51.2) prescriptions in Louisiana and 53.9 (11.0) in Washington. In synthetic control models, SBPM implementation in Louisiana was associated with an increase of 173.5 (95% CI, 74.3-265.3) quarterly prescription fills per 100 000 Medicaid enrollees during the following year, a relative increase of 534.5% (95% CI, 228.7%-1125.0%). Washington did not experience a significant change in prescription fills following SBPM implementation. In this cross-sectional study, Louisiana experienced substantial increases in HCV medication use among its Medicaid-enrolled population following SBPM implementation, whereas Washington did not. These differences may partially be explained by state-level variation in SBPM implementation, historical restrictions on access to HCV medications, and responses to the COVID-19 pandemic.

Association of Medicaid Managed Care Drug Carve Outs With Hepatitis C Virus Prescription Use

Medicaid enrolls a disproportionate share of US adults with hepatitis C virus (HCV), and most receive Medicaid benefits through managed care organizations (MCOs). Medicaid MCOs often impose stricter requirements to access HCV medications than traditional fee-for-service Medicaid, which may inhibit use. Though Medicaid MCOs generally cover prescription drugs, several states have carved out direct-acting antiviral HCV medications from MCO coverage and opted to cover them under fee-for-service. Whether these carve outs were associated with changes in medication use is unknown. To examine the association between Medicaid-covered HCV medication fills and carve outs of these medications from MCO coverage. This cross-sectional study examined changes in fills of Medicaid-covered direct-acting antiviral HCV medications in 4 states (Indiana, Michigan, New Hampshire, and West Virginia) that carved out these drugs from Medicaid MCOs between 2015 and 2017. A synthetic control approach was used to compare changes in HCV prescription fills between states that did and did not carve out these medications from MCO prescription drug coverage. Data of direct-acting antiviral HCV prescription fills were obtained from the Medicaid State Drug Utilization Data files, January 2015 to June 2020. Data analysis was conducted from November 2020 to June 2021. Carve outs of direct-acting antiviral HCV medications from Medicaid MCO prescription drug coverage. Direct-acting antiviral HCV prescriptions filled per 100 000 Medicaid enrollees. In this cross-sectional study, carve outs were associated with a mean quarterly increase of 22.1 (95% CI, 12.7-34.1) HCV prescriptions per 100 000 Medicaid enrollees, a relative increase of 86.3% compared with synthetic control states. Compared with each state's respective synthetic control, HCV prescription fills were associated with an increase of 11.5 (95% CI, 5.1-19.0) HCV prescription fills per 100 000 Medicaid enrollees per quarter in Indiana, 36.6 (95% CI, 23.5-53.9) in Michigan, 20.7 (95% CI, 11.1-32.8) in West Virginia, and 43.6 (95% CI, 25.9-68.4) in New Hampshire. In this cross-sectional study of data from 39 states and the District of Columbia, carve outs of direct-acting antiviral HCV medications from Medicaid MCO prescription drug coverage were associated with significant increases in HCV medication use. Given their clinical benefits, greater uptake of HCV medication may help improve the health of Medicaid enrollees with HCV and reduce the economic burden of untreated HCV on the US health care system.

Hepatitis C Virus Infection in Persons Who Inject Drugs in the Middle East and North Africa: Intervention Strategies.

There is a high incidence and prevalence of hepatitis C viral infection in persons with or without substance use disorders (SUDs) in the Middle East and North Africa (MENA) region, but only a small number receive comprehensive care. Highly effective direct-acting antiviral (DAA) medications are available at substantially lower costs; however, complete elimination of the hepatitis C virus (HCV) can only be achieved if integrated care strategies target those at highest risk for HCV infection and transmission and improve access to care. Due to the high prevalence of SUD in the MENA region, strategies to eliminate HCV must focus on integrated healthcare across multiple subspecialties, including addiction medicine, psychiatry, infectious diseases, hepatology, and social work. In this invited manuscript, we review the epidemiology of HCV in the MENA region and highlight intervention strategies to attain the WHO’s goal of HCV eradication by 2030.

Association of the Extension for Community Healthcare Outcomes Project With Use of Direct-Acting Antiviral Treatment Among US Adults With Hepatitis C

Direct-acting antiviral (DAA) medications are highly effective in treating hepatitis C virus (HCV) infection. However, use of DAAs in rural and underserved areas is low owing to limited access to specialist physicians with experience in care of HCV infection. Project ECHO (Extension for Community Healthcare Outcomes) is a distance education model that trains primary care physicians to improve access to care for underserved populations with complex diseases such as HCV infection. Evidence on whether Project ECHO is associated with increased DAA use is limited. To examine the association between Project ECHO and use of DAA treatment in patients with HCV infection. This cohort study used data from Medicare beneficiaries who newly sought care for HCV infection between January 1, 2014, and December 31, 2017. Data were analyzed between September and December 2020. Project ECHO. Use of DAA treatment. Discrete-time hazard models with state and year fixed effects were used to examine the association between Project ECHO and DAA use in rural areas and areas with low specialist density. A total of 267 908 patients (mean [SD] age, 60.7 [11.5] years; 57.9% male; 66.6% White patients) were included in the analysis. For every 100 clinicians attending a Project ECHO training, the odds of DAA treatment initiation among patients with HCV infection increased by 9% (adjusted odds ratio [OR], 1.09; 95% CI, 1.07-1.11; P < .001) in nonrural areas with specialist density equaling 0. The association between DAA use and Project ECHO was stronger in areas with lower vs higher specialist density. For every additional 100 Project ECHO participants, the odds of DAA use decreased by 1% as specialist density in the area increased (adjusted OR, 0.99; 95% CI, 0.98-1.00; P = .03). There was no association between Project ECHO and the odds of receiving DAAs among patients in rural vs urban areas (adjusted OR, 1.01; 95% CI, 0.99-1.02; P = .49). In this cohort study, implementation of Project ECHO was associated with increased DAA use in areas with few specialist physicians, suggesting that Project ECHO may enhance access to DAA treatment through expanding the capacity of primary care physicians to treat HCV infection, especially in underserved areas.

Is the Availability of Direct-Acting Antivirals Associated with Increased Access to Hepatitis C Treatment for Homeless and Unstably Housed Veterans?

Hepatitis C virus (HCV) treatment has experienced a rapid transformation in the USA. New direct-acting antiviral (DAA) medications make treatment easier, less toxic, and more successful (90% or greater viral cure) than prior, interferon-based HCV medications. We sought to determine whether DAAs may have improved access to HCV treatment for hard-to-reach populations such as the homeless. In a retrospective study of VA electronic medical record data, a cohort was created of 63,586 veterans with a positive HCV RNA or genotype test taken at any point from January 1, 2012, through December 31, 2016. Patient data were examined for up to 5 years using a discrete time survival model to assess the relationship between their housing status and receipt of HCV medications in 6-month time periods in both the interferon and DAA eras. In the interferon era, the probability of HCV treatment in a given 6-month window among housed veterans, at 6.2% (95% CI: 5.3-7.1%) was significantly higher than among veterans who were homeless or unstably housed; for example, among currently homeless veterans, the probability of treatment initiation, in a given 6-month window, was 2.6% (95% CI: 1.9-3.3%). With the arrival of DAAs, each housing category had an increased probability of treatment initiation. For housed veterans, the probability was 8.6% (95% CI: 8.3-8.9%) while for currently homeless veterans, it was 6.3% (95% CI: 5.7-6.9%). We found a clear indication that the likelihood of treatment initiation was greater for all veterans in the DAA era as compared to the interferon era. However, disparities in treatment initiation rates between housed and homeless veterans that were observed in the interferon era persisted in the DAA era.

Integrated treatment of hepatitis C virus infection among people who inject drugs: A multicenter randomized controlled trial (INTRO-HCV).

The standard pathways of testing and treatment for hepatitis C virus (HCV) infection in tertiary healthcare are not easily accessed by people who inject drugs (PWID). The aim of this study was to evaluate the efficacy of integrated treatment of chronic HCV infection among PWID. INTRO-HCV is a multicenter, randomized controlled clinical trial. Participants recruited from opioid agonist therapy (OAT) and community care clinics in Norway over 2017 to 2019 were randomly 1:1 assigned to the 2 treatment approaches. Integrated treatment was delivered by multidisciplinary teams at opioid agonist treatment clinics or community care centers (CCCs) for people with substance use disorders. This included on-site testing for HCV, liver fibrosis assessment, counseling, treatment, and posttreatment follow-up. Standard treatment was delivered in hospital outpatient clinics. Oral direct-acting antiviral (DAA) medications were administered in both arms. The study was not completely blinded. The primary outcomes were time-to-treatment initiation and sustained virologic response (SVR), defined as undetectable HCV RNA 12 weeks after treatment completion, analyzed with intention to treat, and presented as hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals. Among 298 included participants, 150 were randomized to standard treatment, of which 116/150 (77%) initiated treatment, with 108/150 (72%) initiating within 1 year of referral. Among those 148 randomized to integrated care, 145/148 (98%) initiated treatment, with 141/148 (95%) initiating within 1 year of referral. The HR for the time to initiating treatment in the integrated arm was 2.2 (1.7 to 2.9) compared to standard treatment. SVR was confirmed in 123 (85% of initiated/83% of all) for integrated treatment compared to 96 (83% of initiated/64% of all) for the standard treatment (OR among treated: 1.5 [0.8 to 2.9], among all: 2.8 [1.6 to 4.8]). No severe adverse events were linked to the treatment. Integrated treatment for HCV in PWID was superior to standard treatment in terms of time-to-treatment initiation, and subsequently, more people achieved SVR. Among those who initiated treatment, the SVR rates were comparable. Scaling up of integrated treatment models could be an important tool for elimination of HCV. ClinicalTrials.gov.no NCT03155906.