Achieve Hepatitis C Virus Elimination Research Articles

United States Provider Experiences With Telemedicine for Hepatitis C Treatment: A Nationwide Survey.

Hepatitis C virus (HCV) elimination requires treatment access expansion, especially for underserved populations. Telehealth has the potential to improve HCV treatment access, although data are limited on its incorporation into standard clinical practice. We conducted a cross-sectional, email survey of 598 US HCV treatment providers who had valid email addresses and (1) were located in urban areas and had written ≥ 20 prescriptions for HCV treatment to US Medicare beneficiaries in 2019-2020 or (2) were located in non-urban areas and wrote any HCV prescriptions in 2019-2020. Through email, we notified providers of a self-administered electronic 28-item survey of clinical strategies and attitudes about telemedicine for HCV. We received 86 responses (14% response rate), of which 75 used telemedicine for HCV in 2022. Of those 75, 24% were gastroenterologists/hepatologists, 23% general medicine, 17% infectious diseases and 32% non-physicians. Most (82%) referred patients to commercial laboratories, and 85% had medications delivered directly to patients. Overwhelmingly, respondents (92%) felt that telehealth increases healthcare access, and 76% reported that it promotes or is neutral for treatment completion. Factors believed to be 'extremely' or 'very' important for telehealth use included patient access to technology (86%); patients' internet access (74%); laboratory access (76%); reimbursement for video visits (74%) and audio-only visits (66%). Non-physician licensing and liability statutes were rated 'extremely' or 'very' important by 43% and 44%, respectively. Providers felt that telehealth increases HCV treatment access. Major limitations were technological requirements, reimbursement, and access to ancillary services. These findings support the importance of digital equity and literacy to achieve HCV elimination goals.

A novel multisite model to facilitate hepatitis C virus elimination in people experiencing homelessness

Background/aims: Only a handful of countries are on target to achieve hepatitis C virus (HCV) elimination by 2030. People experiencing homelessness (PEH) remain an important HCV reservoir. The END C study evaluated clinical, patient reported and health economic outcomes of a decentralised integrated model. MethodsThis prospective study assessed a decentralised regional service based at multiple homeless sites in southeast England. Novel linkage-care strategies were utilised. We assessed generic and liver specific health-related quality of life (HRQoL) (SF-12v2; EQ-5D-5L and SFLDQol) pre/post HCV treatment and cost per HCV case detected and cured. Primary outcome was intention-to-treat (ITT) sustained virological response (SVR12). ResultsWe recruited 418 individuals, mean age 44.45 ± 10.6, 78% were male, 74% being currently homeless, current injecting drug use/alcohol use being 25% and 65% respectively. Prevalence of cirrhosis (liver stiffness measurement >12kPa) was 12%. Twenty-eight percent (n=116) were HCV PCR positive, of whom n=105 received direct acting antiviral treatment. ITT SVR12 rates were 81% (95% CI 72%-88%), the only predictor of SVR12 being >80% treatment adherence (OR 20.69, 95% CI 6.227-68.772, p<0.001). HRQoL improved significantly after SVR12: SF-12v2 (General Health, Mental Health, Social Functioning, Mental Health Composite Score p<0.049); SFLDQoL (Symptoms/Effects of Liver Disease, Distress, Loneliness p<0.004) and EQ-5D-5L (Index Score, Visual Analog Scale p<0.001). Costs (British pound 2022) per HCV case detected and per case cured were £359 and £257 respectively. Reinfection rates were 6.82/100 person years. ConclusionThe END C study endorses a multisite decentralised service for PEH enabling excellent linkage to care, high SVR12 rates and significant improvements in generic and liver specific HRQoL, all being achieved at modest costs. Such services are paramount to help achieve HCV elimination. Impact and implicationsIn people experiencing homeless, we found a high prevalence of HCV, alcohol and substance misuse including overdoses and mental health issues. Despite this, an integrated and decentralised service resulted in excellent linkage to care with high SVR12 rates. Even in this complex cohort with multiple comorbidities, SVR12 was associated with significant improvements in both generic and liver specific health-related quality of life. This was all achieved at modest costs in a community setting. Such models of care are feasible, easy to replicate and essential if we are to achieve HCV elimination.

Annual hepatitis C testing and positive tests among gay and bisexual men in Australia from 2016 to 2022: a serial cross-sectional analysis of sentinel surveillance data

ObjectiveGuidelines recommend annual hepatitis C virus (HCV) testing for gay and bisexual men (GBM) with HIV and GBM prescribed HIV pre-exposure prophylaxis (PrEP). However, there is a limited understanding of...

Impact of simplified HCV diagnostic strategies on the HCV epidemic among men who have sex with men in the era of HIV oral pre-exposure prophylaxis in Taiwan: a modelling study.

Simplified hepatitis C virus (HCV) diagnostic strategies have the potential to improve HCV diagnoses and treatment. We aimed to investigate the impact of simplified HCV diagnostic strategies on HCV incidence and its effect on HCV diagnosis and treatment among men who have sex with men (MSM) regardless of HIV status and use of HIV pre-exposure prophylaxis (PrEP) in Taiwan. A compartmental deterministic model was developed to describe the natural history of HCV disease progression, the HCV care cascade and the HIV status and PrEP using among MSM. The model was calibrated to available data for HCV and HIV epidemiology and population demographics in Taiwan. We simulated the epidemic from 2004 and projected the impact of simplified testing strategies on the HCV epidemic among MSM over 2022-2030. Under the current testing approach in Taiwan, total HCV incidence would increase to 12.6 per 1000 person-years among MSM by 2030. Single-visit point-of-care RNA testing had the largest impact on reducing the number of new HCV infections over 2022-2030, with a 31.1% reduction (interquartile range: 24.9%-32.8%). By 2030, single-visit point-of-care HCV testing improved HCV diagnosis to 90.9%, HCV treatment to 87.7% and HCV cure to 81.5% among MSM living with HCV. Compared to status quo, prioritized simplified HCV testing for PrEP users and MSM living with diagnosed HIV had considerable impact on the broader HCV epidemic among MSM. A sensitivity analysis suggests that reinfection risk would have a large impact on the effectiveness of each point-of-care testing scenario. Simplified HCV diagnostic strategies could control the ongoing HCV epidemic and improve HCV testing and treatment among Taiwanese MSM. Single-visit point-of-care RNA testing would result in large reductions in HCV incidence and prevalence among MSM. Efficient risk-reduction strategies will need to be implemented alongside point-of-care testing to achieve HCV elimination among MSM in Taiwan.

Strategies of hepatitis C virus elimination for people who inject drugs receiving opioid agonist therapy in the era of direct‐acting antivirals

AbstractIncreased uptake of hepatitis C virus (HCV) treatment among people who inject drugs (PWID) is critical to achieve HCV elimination goals. This study attempted to observe the influence of different referral strategies among HCV‐infected PWID for direct‐acting antivirals (DAA). From January 2019 to November 2020, approximately 190 PWID regularly received opioid agonist therapies (OAT) in the drug addiction rehabilitation clinic of our institute. Among these, those with positive anti‐HCV were further referred to our hepatology clinics for HCV viremia screening and treatment. According to physician involvement, referral strategies were divided into three models including patient self‐intention referral (SR); intensive referral (IR) where patients were referred by clinicians; and fast‐intensive referral (FIR) where patients were referred by clinicians with a fast‐screening and easy‐treatment program. A total of 121 HCV‐infected PWID were enrolled and 71 (58.7%) of them received the referrals: 16 (22.5%) in the SR model, 36 (50.7%) in the IR model, and 19 (26.8%) in the FIR model. Monthly average referred patient number was 2.7 people in the SR model, 2.8 people in the IR model, and 4.8 people in the FIR model, respectively. Among the 71 referred patients, 64 (90.1%) had detectable HCV viremia with genotype distributions being genotype 1a (G1a) in 23 patients (35.9%), G1b in 10 (15.6%), G2 in 5 (7.8%), G3 in 6 (9.4%), and G6 in 20 (31.3%). Except for three patients who refused treatment, 61 patients underwent and completed DAA treatment including 35 patients for Maviret, 15 for Epclusa, 9 for Harvoni, and 2 for Zepatier. Excluding three patients who were lost to follow‐up and one becoming reinfected, 57 (93.4%) eventually achieved a sustained virologic response. Although HCV treatment uptake among PWID in this hospital‐based setting remained suboptimal, the FIR model with a quick‐to‐screen and easy‐to‐treat program was proven practicable in the hospital setting. Further innovative strategies are required to reach all HCV‐infected PWID receiving OAT.

Hepatitis C Elimination in Rwanda: Progress, Feasibility, and Economic Evaluation

ObjectivesIn 2018, Rwanda launched a national program to eliminate the hepatitis C virus (HCV). We aim to assess the impact of the program to date and identify strategies to achieve the World Health Organization’s HCV elimination goals by 2030. MethodsWe developed a microsimulation model to simulate Rwanda’s HCV epidemic from 2015 through 2050 and evaluated temporal trends in HCV infection, prevalence, mortality, and the total cost of care for scenarios that could achieve HCV elimination by 2030. ResultsBetween 2018 and 2022, over 7 million people were screened for HCV, and 60 000 were treated. The study projected that Rwanda could achieve HCV elimination as early as 2027. A feasible strategy of an annual screening rate of 15% and a treatment rate of 100% would achieve all World Health Organization elimination goals by 2028, requiring screening an additional 4 million people and treating 23 900 patients by 2030. The elimination strategy costs $25 million for screening and diagnosis and $21 million for treatment from 2015 to 2050. The national program would avert 4900 hepatocellular carcinoma cases and 6700 HCV-related deaths and save the health system $25.33 million from 2015 to 2050. ConclusionsRwanda is poised to become one of the first countries in the world to eliminate HCV. Rwanda’s program serves as a blueprint for other countries in the African region. By rapid screening and treatment scale-up (eg, by leveraging HIV platforms) and by drug price negotiations, HCV elimination is not only feasible but can be cost-saving in low-income settings.

Reducing Sample Size While Improving Equity in Vaccine Clinical Trials: A Machine Learning-Based Recruitment Methodology with Application to Improving Trials of Hepatitis C Virus Vaccines in People Who Inject Drugs.

Despite the availability of direct-acting antivirals that cure individuals infected with the hepatitis C virus (HCV), developing a vaccine is critically needed in achieving HCV elimination. HCV vaccine trials have been performed in populations with high incidence of new HCV infection such as people who inject drugs (PWID). Developing strategies of optimal recruitment of PWID for HCV vaccine trials could reduce sample size, follow-up costs and disparities in enrollment. We investigate trial recruitment informed by machine learning and evaluate a strategy for HCV vaccine trials termed PREDICTEE-Predictive Recruitment and Enrichment method balancing Demographics and Incidence for Clinical Trial Equity and Efficiency. PREDICTEE utilizes a survival analysis model applied to trial candidates, considering their demographic and injection characteristics to predict the candidate's probability of HCV infection during the trial. The decision to recruit considers both the candidate's predicted incidence and demographic characteristics such as age, sex, and race. We evaluated PREDICTEE using in silico methods, in which we first generated a synthetic candidate pool and their respective HCV infection events using HepCEP, a validated agent-based simulation model of HCV transmission among PWID in metropolitan Chicago. We then compared PREDICTEE to conventional recruitment of high-risk PWID who share drugs or injection equipment in terms of sample size and recruitment equity, with the latter measured by participation-to-prevalence ratio (PPR) across age, sex, and race. Comparing conventional recruitment to PREDICTEE found a reduction in sample size from 802 (95%: 642-1010) to 278 (95%: 264-294) with PREDICTEE, while also reducing screening requirements by 30%. Simultaneously, PPR increased from 0.475 (95%: 0.356-0.568) to 0.754 (95%: 0.685-0.834). Even when targeting a dissimilar maximally balanced population in which achieving recruitment equity would be more difficult, PREDICTEE is able to reduce sample size from 802 (95%: 642-1010) to 304 (95%: 288-322) while improving PPR to 0.807 (95%: 0.792-0.821). PREDICTEE presents a promising strategy for HCV clinical trial recruitment, achieving sample size reduction while improving recruitment equity.

Screening strategy to advance HCV elimination in Italy: a cost-consequence analysis.

Italy has the greatest burden of hepatitis C virus (HCV) infection in Western Europe. The screening strategy represents a crucial prevention tool to achieve HCV elimination in Italy. We evaluated the cost-consequences of different screening strategies for the diagnosis of HCV active infection in the birth cohort 1948-1968 to achieve the HCV elimination goal. We designed a probabilistic model to estimate the clinical, and economic outcomes of different screening coverage uptakes, considering the direct costs of HCV management according to eachliverfibrosis stage, in the Italian context. A decision probabilistic tree simulates 4years of HCV testing of the 1948-1968 general population birth cohort, (15,485,565 individuals to be tested) considering different coverage rates. A No-screening scenario was compared with two alternative screening scenarios that represented different coverage rates each year: (1) Incremental approach (coverage rates equal to 5%, 10%, 30%, and 50% at years 1, 2, 3, and 4, respectively) and (2) Fast approach (50% coverage rate at years 1, 2, 3 and 4). Overall 106,200 cases were previouslyestimated to have an HCV active infection. A liver disease progression Markov model was considered for an additional 6years (horizon-time 10 years). The highest increased number of deaths and clinical events are reported for the No-screening scenario (21,719 cumulative deaths at the end of ten years; 10,148 cases with HCC and/or 7618 cases with Decompensated Cirrhosis). Following the Fast-screening scenario, the reductions in clinical outcomes and deaths were higher compared with No-screening and Incremental-screening. At ten years time horizon, less than 5696 liver deaths (PSA CI95%: -3873 to 7519), 3,549 HCC (PSA CI95%: -2413 to 4684) and less than 3005 liver decompensations (PSA CI 95%: -2104 to 3907) were estimated compared with the Incremental-scenario. The overall costs of the Fast-screening, including the costs of the DAA and liver disease management of the infected patients for 10years, are estimated to be € 43,107,543 more than no-investment in screening and € 62,289,549 less compared with the overall costs estimated by the Incremental-scenario. It is necessary to guarantee dedicated funds and efficiency of the system for the cost-efficacious screening of the 1948-1968 birth cohort in Italy. A delay in HCV diagnosis and treatment in the general population, yet not addressed for the HCV free-of-charge screening, will have important clinical and economic consequences in Italy.

HepFREEPak: protocol for a multi-centre, prospective observational study examining efficacy and impact of current therapies for the treatment of hepatitis C in Pakistan and reporting resistance to antiviral drugs: study protocol

BackgroundPakistan has one of the highest burdens of Hepatitis C virus (HCV) infection globally. To achieve the World Health Organization’s goals for HCV elimination, there is a need for substantial scale-up in testing, treatment, and a reduction in new infections. Data on the population impact of scaling up treatment is not available in Pakistan, nor is there reliable data on the incidence of infection/reinfection. This project will fill this gap by providing important empirical data on the incidence of infection (primary and reinfection) in Pakistan. Then, by using this data in epidemic models, the study will determine whether response rates achieved with affordable therapies (sofosbuvir plus daclatasvir) will be sufficient to eliminate HCV in Pakistan.MethodsThis prospective multi-centre cohort study will screen 25,000 individuals for HCV antibody (Ab) and RNA (if Ab-positive) at various centers in Pakistan- Karachi (Sindh) and Punjab, providing estimates of the disease prevalence. HCV positive patients will be treated with sofosbuvir and daclatasvir for 12-weeks, (extended to 24-weeks in those with cirrhosis) and the proportion responding to this first-line treatment estimated. Patients who test HCV Ab negative will be recalled 12 months later to test for new HCV infections, providing estimates of the incidence rate. Patients diagnosed with HCV (~ 4,000) will be treated and tested for Sustained Virological Response (SVR). Questionnaires to assess risk factors, productivity, health care usage and quality of life will be completed at both the initial screening and at 12-month follow-up, allowing mathematical modelling and economic analysis to assess the current treatment strategies. Viral resistance will be analysed and patients who have successfully completed treatment will be retested 12 months later to estimate the rate of re-infection.ConclusionThe HepFREEPak study will provide evidence on the efficacy of available and widely used treatment options in Pakistan. It will also provide data on the incidence rate of primary infections and re-infections. Data on incidence risk factors will allow us to model and incorporate heterogeneity of risk and how that affects screening and treatment strategies. These data will identify any gaps in current test-and-treat programs to achieve HCV elimination in Pakistan.Study registrationThis study was registered on clinicaltrials.gov (NCT04943588) on June 29, 2021.

Chronic hepatitis C elimination prison initiative: HCV-intensive test and treat, a whole prisoner population HCV test-and-treat program in England.

Prison residents are at high risk for hepatitis C virus (HCV) infection. HCV test-and-treat initiatives within prisons provide an opportunity to engage with prison residents and achieve HCV micro-elimination. The aim of the prison HCV-intensive test and treat initiative was to screen over 95% of all prison residents for HCV infection within a defined number of days determined by the size of the prison population and to initiate treatment within 7-14 days of a positive HCV RNA diagnosis. An HCV-intensive test and treat toolkit was developed based on learnings from pilot HCV-intensive test and treat events. From January 2020 to September 2021, 13 HCV-intensive test and treat events took place at prisons in England selected based on high levels of reception blood-borne virus testing and good access to peers from The Hepatitis C Trust. Among a total of 8487 residents, 8139 (95.9%) underwent testing for HCV. Across the 13 prisons included, HCV antibody and RNA prevalence was 8.2% and 1.5%, respectively. The treatment initiation rate among HCV RNA-positive individuals (n = 124) was 79.0%. The HCV-intensive test and treat initiative presented here provides a feasible and rapid test-and-treat process to achieve HCV elimination within individual prisons. The HCV-intensive test and treat toolkit can be adapted for rapid HCV testing and treatment events at other prisons in the United Kingdom and worldwide.

Hepatitis C virus micro-elimination in people who inject drugs: Challenges and chance in Taiwan and worldwide.

With the introduction of direct-acting antivirals, elimination of hepatitis C virus (HCV) infection is becoming possible. People who inject drugs (PWID) represent a population with a high risk for HCV infection, which has been reported as high as 90% in Taiwanese PWID. To reach the goal of HCV elimination, PWID is a key population deserving special attention. Barriers in HCV care cascade still exist in PWID, and interventions to promote access to HCV diagnosis, link-to-care, treatment, and prevention for PWID are warranted. Although HCV micro-elimination can be achieved in some prisons and opioid substitution therapy (OST) centers by a multidisciplinary team and integrated care in Taiwan, there are still several unmet needs for HCV elimination in PWID. Continuous efforts, such as the participation of OST specialists and the continuum of care for HCV among PWID, are needed to achieve HCV elimination in Taiwan. In addition, the combination of harm reduction services, treatment as prevention and regular posttreatment HCV surveillance is critical to substantially reduce HCV transmission and prevalence in PWID.

Planning, implementing, and evaluating Hepatitis C virus elimination via collaborative community-based care cascade: age–period–cohort model for estimating demand from antecedent anti-HCV survey

BackgroundEstimating the demand for HCV care cascade plays an important role in planning, monitoring, and assessing the performance of introducing a new community-based hepatitis C virus (HCV) elimination program but such an analytic and systematic approach has been barley addressed.MethodsA new collaborative care program for HCV elimination in the Changhua Community of Taiwan has been offered to a total of 895,353 residents since 2018. To grasp the variation of demand for HCV care cascade across demographic and geographic features in the planning stage, we applied the age–period–cohort spatial model to the antecedent anti-HCV survey enrolling 123,617 participants aged 30 years or older between 2005 and 2018. Based on this precise denominator, we then employed a “before-and-after” study design to routinely evaluate whether the WHO criteria of 90% RNA positive diagnosis and 80% successful treatments could be reached.ResultsThe overall demand for HCV care cascade was 4.28% (HCV infection) of the underlying population but a declining trend was noted. The early cohort had a higher demand, whereas the demand of the young cohort decreased with each passing year. The demand also differed by township. The demand, allowing for these variations, for antiviral treatment was 22,362, yielding the WHO target of 12,880 for achieving HCV elimination. With 11,844 successful treatments, the effectiveness of elimination has already reached 92% (11,844/12,880) by the end of 2022.ConclusionsThe demand for HCV care cascade allows health care decision-makers to timely and properly assess the performance of a novel community-based collaborative care program in achieving HCV elimination.

What Is Needed to Move Toward Single-Step Diagnosis of Current HCV Infection?

Despite remarkable therapeutic advances, hepatitis C virus (HCV) infection continues to be a major global problem. While the development of highly effective direct-acting antivirals has ensured that almost all those who are treated achieve viral cure, progress toward HCV elimination globally has stalled due to challenges upstream of treatment in the cascade of care, namely diagnosis and linkage to care. The major challenge continues to be the relative complexity of HCV diagnosis with the current requirement for a confirmatory HCV RNA test after an initial antibody-positive result. In this review, challenges with the current paradigm are highlighted with a focus on new technologies, as well as simple strategies using existing tools, which may simplify diagnosis and improve linkage to care and treatment. To achieve HCV elimination, improvements in the HCV diagnostics field to allow for a simple single-step diagnosis are required.

Reported adverse events related to use of hepatitis C virus direct-acting antivirals with opioids: 2017–2021

IntroductionDue to concerns over potential interactions between some hepatitis C direct-acting antivirals (DAAs) and opioids, we describe adverse event (AE) reports of concomitant use of opioids and DAAs.MethodsAEs reported (July 28, 2017–December 31, 2021) with the administration of the DAAs glecaprevir/pibrentasvir, sofosbuvir/velpatasvir, ledipasvir/sofosbuvir, sofosbuvir/velpatasvir/voxilaprevir, and elbasvir/grazoprevir as suspect products were downloaded from the US Food and Drug Administration AE Reporting System Public Dashboard. The number of AE reports containing opioids (fentanyl, hydrocodone, oxycodone) as co-suspect products/concomitant products were counted and summarized by severity, reporting country and whether an outcome of death was reported. Overdose AEs were counted irrespective of opioid use, and changes over time were assessed.ResultsIn total, 40 AEs were reported for DAAs and concomitant fentanyl use, 25 (62.5%) were in the USA, 35 (87.5%) were considered serious, and 14 (35.0%) resulted in death; and 626 were reported with concomitant oxycodone/hydrocodone use, 596 (95.2%) were in the USA, 296 (47.3%) were considered serious, and 28 (4.5%) resulted in death. There were 196 overdose AEs (32 [16%] deaths) declining from 2018 (N = 56) to 2021 (N = 29).ConclusionsTreating people with hepatitis C virus (HCV) infection who use drugs is key to achieving HCV elimination. Low numbers of DAA AE reports with opioids may provide reassurance to prioritize HCV treatment in this population. These data contribute to evidence supporting the continued scale-up of DAA treatment among people who use drugs to achieve HCV elimination goals.

Tools Needed to Support Same-Day Diagnosis and Treatment of Current Hepatitis C Virus Infection.

The current multiday diagnosis and treatment paradigm for hepatitis C virus (HCV) infection results in far fewer patients receiving treatment with direct-acting antiviral agents than those with diagnosed HCV infection. To achieve HCV elimination, a paradigm shift in access to HCV treatment is needed from multiday testing and treatment algorithms to same-day diagnosis and treatment. This shift will require new tools, such as point-of-care (POC) antigen tests or nucleic acid tests for HCV and hepatitis B virus (HBV) and nucleic acid tests for human immunodeficiency virus (HIV) that do not require venous blood. This shift will also require better use of existing resources, including expanded access to HCV treatment and available POC tests, novel monitoring approaches, and removal of barriers to approval. A same-day diagnosis and treatment paradigm will substantially contribute to HCV elimination by improving HCV treatment rates and expanding access to treatment in settings where patients have brief encounters with healthcare.

Simplified Test-to-Treat Strategy for Hepatitis C in Thailand: The Phetchabun Model.

The complexity of the hepatitis C virus (HCV) diagnostic workflow and stringent criteria for universal health coverage are significant barriers to achieving HCV elimination in Thailand. A test-to-treat strategy using a rapid diagnostic test (RDT) for screening at point of care, followed by a qualitative nucleic acid testing, is a promising strategy to facilitate population-wide screening for HCV infection and expedite time to treatment. This strategy was evaluated in Phetchabun province, Thailand, where the HCV burden is relatively high. This simplified HCV test-to-treat strategy showed strong potential to be implemented at a national level. Several obstacles to implementation included the stringent criteria for universal health coverage, which prioritizes patients with advanced disease, the continuous policy revision for HCV treatment and care, the relatively low public awareness of HCV infection, and the lagging of government policy prioritization. All of these contribute to the delayed progress in hepatitis elimination.

Assessment of Drug-Drug Interaction Risk Between Intravenous Fentanyl and the Glecaprevir/Pibrentasvir Combination Regimen in Hepatitis C Patients Using Physiologically Based Pharmacokinetic Modeling and Simulations.

An unsafe injection practice is one of the major contributors to new hepatitis C virus (HCV) infections; thus, people who inject drugs are a key population to prioritize to achieve HCV elimination. The introduction of highly effective and well-tolerated pangenotypic direct-acting antivirals, including glecaprevir/pibrentasvir (GLE/PIB), has revolutionized the HCV treatment landscape. Glecaprevir is a weak cytochrome P450 3A4 (CYP3A4) inhibitor, so there is the potential for drug-drug interactions (DDIs) with some opioids metabolized by CYP3A4, such as fentanyl. This study estimated the impact of GLE/PIB on the pharmacokinetics of intravenous fentanyl by building a physiologically based pharmacokinetic (PBPK) model. A PBPK model was developed for intravenous fentanyl by incorporating published information on fentanyl metabolism, distribution, and elimination in healthy individuals. Three clinical DDI studies were used to verify DDIs within the fentanyl PBPK model. This model was integrated with a previously developed GLE/PIB PBPK model. After model validation, DDI simulations were conducted by coadministering GLE 300mg + PIB 120mg with a single dose of intravenous fentanyl (0.5µg/kg). The predicted maximum plasma concentration ratio between GLE/PIB + fentanyl and fentanyl alone was 1.00, and the predicted area under the curve ratio was 1.04, suggesting an increase of only 4% in fentanyl exposure. The administration of a therapeutic dose of GLE/PIB has very little effect on the pharmacokinetics of intravenous fentanyl. This negligible increase would not be expected to increase the risk of fentanyl overdose beyond the inherent risks related to the amount and purity of the fentanyl received during recreational use.

Evaluation and comparison of risk-based and universal prenatal HCV screening programs in Alberta, Canada

Canadian clinical practice guidelines currently recommend risk-based screening for hepatitis C virus (HCV) in pregnant individuals. However, no provinces or territories have ever compared the effectiveness of risk-based versus universal screening for diagnosing prenatal HCV. We aimed to evaluate and compare HCV screening programs after implementing a universal population-level pilot program among prenatal patients in Alberta, Canada. The Alberta Prenatal Screening Program for Select Communicable Diseases was amended to include universal HCV antibody screening. Cohorts of pregnant individuals screened for HCV through risk-based or universal programs were generated over one-year periods. HCV screening rates and prevalence was analyzed and compared between cohorts to evaluate effectiveness of screening methods. Social and demographic risk factors for HCV positive individuals were compared between screening cohorts to identify which populations may be overlooked with risk-based guidelines. HCV antibody screening rates were 11.9% and 99.9% among pregnant individuals in the risk-based and universal cohorts respectively. HCV prevalence among the cohorts was 0.07% and 0.11% (difference=0.04%, p=0.032), with an average of 21 additional HCV positive pregnant individuals identified annually with universal screening. HCV positive prenatal patients diagnosed through universal screening were more likely to engage in high-risk sexual behaviours/sex work compared to those diagnosed through risk-based screening (47.6% versus 12.5%, respectively p=0.035), suggesting risk-based screening is missing these high-risk women. Universal HCV screening diagnoses significantly higher numbers of pregnant individuals infected with HCV compared to risk-based screening. Universal HCV screening or amending risk-based guidelines to incorporate more proxy variables for risk factors should be considered to improve prenatal HCV screening guidelines in Canada and help achieve HCV elimination in the next decade. Hepatitis C virus (HCV) is a bloodborne pathogen that can cause severe liver disease and be vertically transmitted from a mother to her baby during pregnancy. Pregnant individuals in Alberta are currently only tested for HCV if they disclose to their physician engagement in activities that put them at risk for acquiring the infection (risk-based screening). Using a population-wide universal prenatal HCV screening program, our work shows testing based on patient disclosed risk alone significantly underdiagnoses HCV in pregnant individuals and suggests individuals engaging in sex work or risky sexual behaviours are being overlooked with the current risk-based program. Our outcomes represent the first province-wide study to evaluate and compare prenatal HCV risk-based and universal screening programs in Canada and can be used as evidence-based data for updating prenatal HCV screening policies across the country and in similar jurisdictions.

Investigating rates and risk factors for hepatitis C virus reinfection in people receiving antiviral treatment in England.

England has committed to the World Health Organization target to eliminate hepatitis C virus (HCV) as a public threat by the year 2030. Given successful treatments for HCV in recent years, it is unclear whether HCV reinfection will impact England's ability to achieve HCV elimination. We aimed to estimate the HCV reinfection rate among a cohort of patients receiving antiviral treatment using available surveillance data. Linkage between a treatment dataset from 2015 to 2019 and an HCV RNA testing dataset were used to identify people who experienced reinfection using three criteria. A Cox proportional hazards model was used to determine risk factors associated with HCV reinfection among a cohort who received treatment and had follow-up HCV RNA testing. The reinfection rate among those receiving HCV treatment was 7.91 per 100 person-years (PYs, 95% confidence interval (CI) 7.37-8.49) and highest among current injecting drug users (22.55 per 100 PYs, 95% CI 19.98-25.46) and people who had been in prison (20.42 per 100 PYs, 95% CI 17.21-24.24). In the adjusted model, women had a significantly reduced risk of reinfection. Being of younger age, current injecting drug users, and receipt of first treatment in prison were each significantly associated with increased risk of reinfection. Two-fifths of those with reinfection (43%, n=329/767) were linked to treatment after reinfection, and of those starting treatment, three quarters (75%, n=222/296) achieved a sustained virologic response. Guidance for testing groups at risk of reinfection and harm reduction strategies to minimize transmission should be implemented if England is to achieve HCV elimination targets.

Hepatitis C testing among three distinct groups of gay, bisexual and other men who have sex with men: a cross-sectional study in the Celtic nations

ObjectiveThe hepatitis C virus (HCV) epidemic among gay, bisexual and other men who have sex with men (GBMSM) is associated with sexual and drug-related behaviours. To stem the tide of...