Effective Direct-acting Antivirals Research Articles

Seroprevalence of Hepatitis C virus (HCV) infection and role of serological and molecular assay in HCV detection and management: A step towards achieving the aim of National Viral Hepatitis Control Program (NVHCP)

Purpose: Hepatitis C virus (HCV) is a small, enveloped, single stranded RNA virus of Flaviviridae family. HCV causes both acute and chronic infection. Diagnosis of HCV can be done by indirect serological tests that detect antibodies against HCV (anti-HCV) and direct test that detects and quantifies components of viral RNA particles. As per CDC recommendation; HCV testing should be initiated with anti-HCV test, those anti-HCV positive/reactive should have follow-up testing with Nucleic Acid Test. If the HCV RNA is detected, patient should be directed for the treatment with highly effective direct acting antiviral (DAA). This study aims to determine the seroprevalence of HCV infection, to estimate presumptive HCV infection by using serological assay by anti-HCV ELISA, to estimate the current HCV infection by detecting HCV-RNA using RT-PCR molecular assay and, to highlight the role of HCV RNA for initiation of treatment. Methods: This study is retrospective observational analysis of 36500 samples obtained for anti-HCV ELISA test from Jan to Dec 2022. The ELISA kit used was a 3rd generation sandwich assay. All ELISA positive samples were tested for HCV RNA, by automated qRT-PCR method. Results: Out of 36500 samples, 361 tested positive by anti-HCV ELISA with 0.9% seroprevalence. Out of 361, only 336 were tested for HCV RNA. Of 336, 240 samples were negative as target not detected, and 96 samples showed values as viral copies in IU/mL. Most common age group affected was 18-40 years, for both serology and molecular test. Conclusion: In current study, only 96 samples showed viral copies indicating current HCV infection and need to start treatment. Hepatitis C is curable; with the availability of highly effective DAA both in a brand and generic form can cure > 95% of infected people, so the possibility of achieving the target of elimination HCV by 2030 can be predicted.

Chronic Hepatitis C Infection Treated with Direct-Acting Antiviral Agents and Occurrence/Recurrence of Hepatocellular Carcinoma: Does It Still Matter?

Hepatitis C virus (HCV) infection is a significant risk factor for liver cirrhosis and hepatocellular carcinoma (HCC). Traditionally, the primary prevention strategy for HCV-associated HCC has focused on removing infection through antiviral regimes. Currently, highly effective direct-acting antivirals (DAAs) offer extraordinary success across all patient categories, including cirrhotics. Despite these advancements, recent studies have reported that even after sustained virologic response (SVR), individuals with advanced liver disease/cirrhosis at the time of DAA treatment may still face risks of HCC occurrence or recurrence. Based on this premise, this review tries to shed light on the multiple mechanisms that establish a tumorigenic environment, first, during chronic HCV infection and then, after eventual viral eradication by DAAs. Furthermore, it reviews evidence reported by recent observational studies stating that the use of DAAs is not associated with an increased risk of HCC development but rather, with a significantly lower chance of liver cancer compared with DAA-untreated patients. In addition, it seeks to provide some practical guidance for clinicians, helping them to manage HCC surveillance of patients who have achieved SVR with DAAs.

Loss to follow-up of patients after antiviral treatment as an additional barrier to HCV elimination

BackgroundEliminating hepatitis C virus (HCV) infections is a goal set by the World Health Organization. This has become possible with the introduction of highly effective and safe direct-acting antivirals (DAA) but limitations remain due to undiagnosed HCV infections and loss of patients from the cascade of care at various stages, including those lost to follow-up (LTFU) before the assessment of the effectiveness of the therapy. The aim of our study was to determine the extent of this loss and to establish the characteristics of patients experiencing it.MethodsPatients with chronic HCV infection from the Polish retrospective multicenter EpiTer-2 database who were treated with DAA therapies between 2015 and 2023 were included in the study.ResultsIn the study population of 18,968 patients, 106 had died by the end of the 12-week post-treatment follow-up period, and 509 patients did not report for evaluation of therapy effectiveness while alive and were considered LTFU. Among patients with available assessment of sustained virological response (SVR), the effectiveness of therapy was 97.5%. A significantly higher percentage of men (p<0.0001) and a lower median age (p=0.0001) were documented in LTFU compared to the group with available SVR assessment. In LTFU patients, comorbidities such as alcohol (p<0.0001) and drug addiction (p=0.0005), depression (p=0.0449) or other mental disorders (p<0.0001), and co-infection with human immunodeficiency virus (HIV) (p<0.0001) were significantly more common as compared to those with SVR assessment. They were also significantly more often infected with genotype (GT) 3, less likely to be treatment-experienced and more likely to discontinue DAA therapy.ConclusionsIn a real-world population of nearly 19,000 HCV-infected patients, we documented a 2.7% loss to follow-up rate. Independent predictors of this phenomenon were male gender, GT3 infection, HIV co-infection, alcohol addiction, mental illnesses, lack of prior antiviral treatment and discontinuation of DAA therapy.

Inflammatory Consequences: Hepatitis C Virus-Induced Inflammasome Activation and Pyroptosis.

Hepatitis C virus (HCV), despite the availability of effective direct-acting antivirals (DAAs) that clear the virus from >95% of individuals treated, continues to cause significant health care burden due to disease progression that can lead to fibrosis, cirrhosis, and/or hepatocellular carcinoma. The fact that some people who are treated with DAAs still go on to develop worsening liver disease warrants further study into the immunopathogenesis of HCV. Many viral infections, including HCV, have been associated with activation of the inflammasome/pyroptosis pathway. This inflammatory cell death pathway ultimately results in cell lysis and release of inflammatory cytokines, IL-18 and IL-1β. This review will report on studies that investigated HCV and inflammasome activation/pyroptosis. This includes clinical in vivo data showing elevated pyroptosis-associated cytokines in the blood of individuals living with HCV, studies of genetic associations of pyroptosis-related genes and development of liver disease, and in vitro studies aimed at understanding the mechanism of pyroptosis induced by HCV. Finally, we discuss major gaps in understanding and outstanding questions that remain in the field of HCV-induced pyroptosis.

Pregnancy as an Opportunity for Hepatitis C Virus Elimination and Eradication.

Since the development of highly effective direct-acting antivirals, the WHO has set a goal of hepatitis C virus (HCV) elimination by 2030. Key to this strategy is increased screening and treatment. Pregnancy and the postpartum period represent a unique time when underserved populations have increased contact with the healthcare system. We propose using antenatal care to maximize case identification, treatment, and prevention. Pregnant individuals are an ideal sentinel population for HCV surveillance. Universal screening in pregnancy can provide population-level data. Once cases are identified, pregnancy presents an opportunity for intervention. Although not currently WHO approved, clinical trials are examining treatment during pregnancy. In the interim, identification of infection during pregnancy allows for optimization of the treatment cascade postpartum. Pregnancy can be used as a time for prevention. Taking advantage of patient engagement and existing infrastructure, pregnancy presents an opportunity to intervene in the fight for HCV eradication.

2490. Improving Hepatitis C Continuum of Care in an Outpatient Internal Medicine Population

Abstract Background According to the WHO, approximately 71 million people are infected with Hepatitis C virus (HCV), and more than 400,000 people die each year due to HCV-related liver diseases. Since the advent of safe and highly effective direct-acting antivirals (DAA) in 2014, treatment for HCV has been revolutionized with cure rates exceeding 90%. Although the detection of undiagnosed HCV infection itself likely has some inherent benefit, the impact of screening is greatly reduced if it does not lead to treatment and cure. Studies on the HCV continuum of care have concluded many patients are lost at each stage, highlighting the need to raise awareness among healthcare professionals and at-risk populations about hepatitis testing, referral, support, and care. A practical model to help fill care gaps in urban internal medicine clinics and improved treatment enrollment and adherence is necessary, which in turn will improve public health outcomes. Methods The objective of the study is to improve the continuum of care of HCV, from diagnosis to treatment of the disease at the outpatient Faculty Medical Center (FMC) Internal Medicine Clinic, and identify hurdles to treatment. We enrolled 31 patients who screened positive for hepatitis C antibody into a pooled cohort, where biweekly telephone encounters were initiated for 3 months to facilitate close follow-up, including scheduling labs and office visits and facilitating subspecialty referrals. (Table 1). Hepatitis C Continuum of Care Workflow HCV labs include HCV viral load and genotype, Fibroscan, Hepatitis B surface antigen, and antibody, Hepatitis A antibody, and HIV 1/2 antibody test. Results Six months post-study, 7 out of 31 (22%) patients enrolled in our intensive follow-up completed treatment. Among the patients who were lost to follow-up, the most common issue encountered was following up with specialists (58%). The most common communication barrier was patients having inactive phone numbers. Results Conclusion Our next step is to establish an HCV clinic within our FMC Internal Medicine Center to expand access to care for HCV-affected patients. The HCV clinic will include coordination with the Infectious Diseases specialist through E-Consult and TriHealth Specialty Pharmacy. The impact will be early treatment of HCV-affected patients, improved treatment success which ultimately reduces the risk of transmission and progression of the disease, and improved quality of life. Disclosures All Authors: No reported disclosures

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.

Construction and characterization of a new hepatitis C virus genotype 6a subgenomic replicon that is prone to render the sofosbuvir resistance.

Hepatitis C virus (HCV) infection remains a challenge to human public health despite the development of highly effective direct-acting antivirals (DAAs). Sofosbuvir (SOF), a key component in most DAA-based anti-HCV cocktail regimens, is a potent viral RNA polymerase (NS5B) inhibitor with a high barrier to drug resistance. The serine-to-threonine mutation at NS5B 282 (S282T) confers the SOF resistance, but severely impairs viral replication in most HCV genotypes (GTs) and cannot be stably maintained after the termination of the SOF-based therapies. In this study, we first developed a new HCV GT-6a subgenomic replicon PR58D6. Next, we selected SOF-resistant PR58D6 variants by culturing the replicon cells in the presence of SOF. Interestingly, unlike many other HCV replicons which require additional mutations to compensate for the S282T-inducing fitness loss, S282T alone in PR58D6 is genetically stable and confers the SOF resistance without significantly impairing viral replication. Furthermore, we showed that amino acid residue at NS5B 74 (R74) and 556 (D556) which are conserved in GT 6a HCV contribute to efficient replication of PR58D6 containing S282T. Finally, we showed that the G556D mutation in NS5B could rescue the replication deficiency of the S282T in JFH1, a GT-2a replicon. In conclusion, we showed that a novel GT-6a HCV replicon may easily render SOF resistance, which may call for attention to potential drug resistance during DAA therapies of HCV GT-6a patients.

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.

How Can We Predict Disease Severity in Viral Infections?

How Can We Predict Disease Severity in Viral Infections?

Editorial: Effective Direct-Acting Antiviral Treatments Support Global and National Programs to Eliminate Hepatitis C

Eliminating an infectious disease aims to result in no residual disease in a specific geographic area due to deliberate efforts, which may require ongoing control measures to prevent the re-establishment of infection transmission. Currently, no effective vaccines prevent hepatitis C virus (HCV) infection. However, during the past decade, oral direct-acting antivirals (DAAs) have been developed and approved for the treatment of HCV that result in a 'cure' in more than 95% of people infected. Morbidity and mortality from untreated hepatitis C result from liver failure, cirrhosis, and HCC and can be prevented by curative treatment with DAAs, which also prevents HCV transmission. Morbidity and mortality from untreated hepatitis C result from liver failure, cirrhosis, and HCC and can be prevented by curative treatment with DAAs, which also prevents HCV transmission. In May 2016, the World Health Assembly of the World Health Organization (WHO) proposed the first global health initiative on viral hepatitis, which proposed the elimination of hepatitis B and C by 2030. In March 2023, the US President announced that in the 2024 fiscal year budget proposal, a 5-year program was approved to eliminate hepatitis C in the US, using a screening and treatment approach. This Editorial aims to present the development of effective and curative DAA treatments for hepatitis C that support the WHO and US Federal programs for disease elimination.

Combining treatment for chronic hepatitis C with opioid agonist therapy is an effective microelimination strategy for people who inject drugs with high risk of non-adherence to direct-acting antiviral therapy

Despite effective direct-acting antivirals (DAAs), hepatitis C virus (HCV) prevalence is high among people who inject drugs (PWIDs) and non-adherence to therapy remains a major obstacle towards HCV elimination in this subpopulation. To overcome this issue, we have combined ongoing opioid agonist therapy (OAT) with DAAs in a directly-observed therapy (DOT) setting. From September 2014 until January 2021 PWIDs at high risk of non-adherence to DAA therapy, who were also on OAT, were included into this microelimination project. Individuals received their OAT and DAAs under supervision of healthcare workers as DOT in a pharmacy or low-threshold facility. In total, 504 HCV RNA-positive PWIDs on OAT (387 men, 76.8%; median age: 38 years [IQR 33-45], HIV: 4.6%; hepatitis B: 1.4%) were included into this study. Two thirds reported ongoing intravenous drug use (IDU) and half of them had no permanent housing. Only 41 (8.1%) were lost to follow-up and two (0.4%) died of reasons unrelated to DAA toxicity. Overall, 90.7% of PWIDs achieved sustained virological response 12 weeks after treatment (SVR12) (95% CI: 88.1-93.2%). By excluding those lost to follow-up and hose who had died of causes unrelated to DAAs, the SVR12 rate was 99.1% (95% CI: 98.3-100.0%; modified intention-to-treat analysis). Four PWIDs (0.9%) experienced treatment failure. Over a median follow-up of 24 weeks (IQR 12-39), 27 reinfections (5.9%) were observed in individuals with the highest IDU rates (81.2%). Importantly, even though some were lost to follow-up, all completed their DAA treatment. By using DOT, adherence to DAAs was excellent with only a total of 86 missed doses (0.3% of 25,224 doses). In this difficult-to-treat population of PWIDs with high rates of IDU , coupling DAA treatment to OAT in a DOT setting resulted in high SVR12 rates equivalent to conventional treatment settings in non-PWID populations.

Molecular characterization and genotyping of hepatitis C virus from Sudanese end-stage renal disease patients on haemodialysis

BackgroundHepatitis C virus (HCV) is a global public health problem, with ~ 11 million people in Africa infected. There is incomplete information on HCV in Sudan, particularly in haemodialysis patients, who have a higher prevalence compared to the general population. Thus, our objectives were to genotype and molecularly characterize HCV isolated from end-stage renal disease haemodialysis patients.MethodsA total of 541 patients were recruited from eight haemodialysis centres in Khartoum and screened for anti-HCV. Viral loads were determined using in-house real-time PCR in seropositive patients. HCV was genotyped and subtyped using sequencing of amplicons of 5′ untranslated (UTR) and non-structural protein 5B (NS5B) regions, followed by phylogenetic analysis of corresponding sequences.ResultsThe HCV seroprevalence in the study was 17% (93/541), with HCV RNA-positive viremic rate of 7% (40/541). A low HCV load, with a mean of 2.85 × 104 IU/ml and a range of 2.95 × 103 to 4.78 × 106 IU/ml, was detected. Phylogenetic analyses showed the presence of genotypes 1, 3, 4, and 5 with subtypes 1a, 1b, 1 g, 3a, 4a, 4 l, 4 m, 4 s, and 4t. Sequences of HCV from the same haemodialysis units, clustered in similar genotypes and subtypes intimating nosocomial infection.ConclusionHCV infection is highly prevalent in haemodialysis patients from Sudan, with phylogenetic analysis intimating nosocomial infection. HCV genotyping is useful to locate potential transmission chains and to enable individualized treatment using highly effective direct-acting antivirals (DAAs).

Hepatitis C Virus Infections in Patients with Hemophilia: Links, Risks and Management.

Haemophilia is a rare, hereditary bleeding disorder. Clotting factor concentrates were a revolutionary treatment which changed the life of people with haemophilia. However, early generation of clotting factor concentrates, without viral inactivation procedures in the manufacturing process, led to an increased risk of transmission of blood-borne viral infections, mainly due to hepatitis C virus and human immunodeficiency virus. As only 20% of HCV-infected patients clear the infection naturally, chronic HCV infection constitutes a serious health problem and a major cause of chronic liver disease in this group of patients. Fortunately, the use of viral inactivation procedures in the plasma-derived factor concentrates manufacturing process and the availability of alternative treatment options, led to a significant reduction of transfusion-associated viral infections. The advent of multiple, orally administrated, highly effective direct-acting antivirals (DAAs) is changing the natural history of HCV infection in patients with haemophilia as these drugs have an excellent safety profile and achieve very high sustained virological response rates, similar to the general population. Eradication of HCV-infection in patients with haemophilia is feasible via micro-elimination projects.

Efficacy and Safety of a Botanical Formula Fuzheng Huayu for Hepatic Fibrosis in Patients with CHC: Results of a Phase 2 Clinical Trial.

Background Hepatitis C virus (HCV) is a common cause of progressive hepatic fibrosis, cirrhosis, and hepatocellular carcinoma worldwide. Despite the availability of effective direct-acting antivirals, patients often have significant hepatic fibrosis at the time of diagnosis due to delay in diagnosis and comorbidities which promote fibrogenesis. Thus, antifibrotic agents represent an attractive adjunctive therapy. Fuzheng Huayu (FZHY), a traditional Chinese medicine botanical formulation, has been used as an antifibrotic agent in chronic HBV infection. Our aim was to assess FZHY in patients with HCV infection and active viremia. Method We randomized 118 patients with active viremia from 8 liver centers in the U.S. to receive oral FZHY (n = 59) or placebo (n = 59) for 48 weeks. Efficacy was assessed by histopathologic changes at the end of therapy. A subset of biopsies was further analyzed using qFibrosis to detect subtle changes in fibrosis in different zones of the hepatic lobules. Results FZHY was well tolerated and safe. Patients with baseline Ishak fibrosis stages F3 and F4 had better response rates to FZHY than patients with baseline F0–F2 (p=0.03). qFibrosis zonal analysis showed significant improvement in fibrosis in all zones in patients with regression of the fibrosis stage. Conclusions FZHY produced antifibrotic effects in patients with baseline Ishak F3 and F4 fibrosis stages. Reduction in fibrosis severity was zonal and correlated with the severity of inflammation. Based on its tolerability, safety, and efficacy, FZHY should be further investigated as a therapy in chronic liver diseases because of its dual anti-inflammatory and antiibrotic properties. Lay Summary. This is the first US-based, multicenter and placebo-controlled clinical trial that shows statistically significant reduction in fibrosis in patients with active HCV using an antifibrotic botanical formula. This has important implications as there is an immediate need for effective antifibrotic agents in treating many chronic diseases including NASH that lead to scarring of the liver. With artificial intelligence-based methodology, qFibrosis, we may provide a more reliable way to assess the FZHY as a therapy in chronic liver diseases because of its dual anti-inflammatory and antifibrotic properties.

Hepatitis C: diagnosis, treatment and harm‐reduction strategies

The introduction of new and effective direct‐acting antivirals has revolutionised the treatment of hepatitis C over the last decade. Part 2 of this two‐part series on the management of hepatitis C provides an overview of these new treatments, as well as discussing hepatitis C diagnosis and harm‐reduction strategies.

Performance of Hepatitis C Virus (HCV) Core Antigen Assay in the Diagnosis of Recently Acquired HCV Infection among High-Risk Populations.

ABSTRACTHow the hepatitis C virus (HCV) core antigen (HCVcAg) assay performs in detecting recently acquired HCV infection among people living with HIV (PLWH) and HIV-negative men who have sex with men (MSM) is rarely assessed in the Asia-Pacific region. High-risk participants, including PLWH with sexually transmitted infections (STIs), HCV clearance by antivirals or spontaneously, or elevated aminotransferases, HIV-negative MSM with STIs or on HIV preexposure prophylaxis, and low-risk PLWH were enrolled. Blood samples were subjected to 3-stage pooled-plasma HCV RNA testing every 3 to 6 months until detection of HCV viremia or completion of the 1-year follow-up. The samples at enrollment and all of the archived samples preceding the detection of HCV RNA during follow-up were tested for HCVcAg. During June 2019 and February 2021, 1,639 blood samples from 744 high-risk and 727 low-risk PLWH and 86 HIV-negative participants were tested for both HCV RNA and HCVcAg. Of 62 samples positive for HCV RNA, 54 (87.1%) were positive for HCVcAg. Of 1,577 samples negative for HCV RNA, 1,568 (99.4%) were negative for HCVcAg. The mean HCV RNA load of the 8 individual samples positive for HCV RNA but negative for HCVcAg was 3.2 (range, 2.5 to 3.9) log10 IU/mL, and that of the remaining 54 samples with concordant results was 6.2 (range, 1.3 to 8.5) log10 IU/mL. The positive predictive value (PPV) and negative predictive value (NPV) of HCVcAg were 85.7% and 99.5%, respectively. In at-risk populations, HCVcAg has a high specificity and NPV but lower sensitivity and PPV, particularly in individuals with low HCV RNA loads.IMPORTANCE The HCV core antigen assay has a high specificity of 99.4% and negative predictive value of 99.5% but a lower sensitivity of 87.1% and positive predictive value of 85.7% in the diagnosis of recently acquired HCV infection in high-risk populations. Our findings are informative for many countries confronted with limited resources to timely identify acute HCV infections and provide effective direct-acting antivirals to halt onward transmission.

The Importance of Prisons in Achieving Hepatitis C Elimination: Insights from the Australian Experience.

Following the availability of highly effective direct-acting antivirals (DAAs) to treat hepatitis C infection, the uptake of treatment by people living with hepatitis C rose dramatically in high- and middle-income countries but has since declined. To achieve the World Health Organization’s (WHO) 2030 target to eliminate hepatitis C as a public health threat among people who inject drugs, an increase in testing and treatment is required, together with improved coverage of harm reduction interventions. The population that remains to be treated in high- and middle-income countries with high hepatitis C prevalence are among the most socially disadvantaged, including people who inject drugs and are involved in the criminal justice system, a group with disproportionate hepatitis C prevalence, compared with people in the wider community. Imprisonment provides an unrivalled opportunity for screening and treating large numbers of people for hepatitis C, who may not access mainstream health services in the community. Despite some implementation challenges, evidence of the efficacy, acceptability, and cost-effectiveness of in-prison hepatitis treatment programs is increasing worldwide, and evaluations of these programs have demonstrated the capacity for treating people in high numbers. In this Perspective we argue that the scale-up of hepatitis C prevention, testing, and treatment programs in prisons, along with the investigation of new and adapted approaches, is critical to achieving WHO elimination goals in many regions; the Australian experience is highlighted as a case example. We conclude by discussing opportunities to improve access to prevention, testing, and treatment for people in prison and other justice-involved populations, including harnessing the changed practices brought about by the COVID-19 pandemic.

Ravidasvir: equitable access through an alternative drug development pathway

The development of highly effective direct-acting antivirals has made it possible to imagine the global elimination of hepatitis C, which afflicts an estimated 58 million people and causes 290 000 deaths globally each year.1 Inspired by this possibility, in 2016, WHO established the goal of eliminating viral hepatitis globally by 2030.2

Population-level estimates of hepatitis C reinfection post scale-up of direct-acting antivirals among people who inject drugs

Background & AimsScale-up of highly effective direct-acting antivirals (DAAs) for HCV among people who inject drugs (PWID) in Scotland has led to a reduction in the prevalence of viraemia in this population. However, the extent of reinfection among those treated with DAAs remains uncertain. We estimated HCV reinfection rates among PWID in Scotland by treatment setting, pre- and post-introduction of DAAs, and the potential number of undiagnosed reinfections resulting from incomplete follow-up testing.MethodsThrough linkage of national clinical and laboratory HCV data, a retrospective cohort of PWID who commenced treatment between 2000-2018 and achieved a sustained virological response (SVR) were followed up for reinfection to December 2019. Reinfection was defined as a positive HCV antigen or RNA test.ResultsOf 5,686 SVRs among 5,592 PWID, 4,126 (73%) had an HCV RNA or antigen test post-SVR. Of those retested, we identified 361 reinfections (3.9/100 person-years [PY]). The reinfection rate increased from 1.5/100 PY among PWID treated in 2000-2009 to 8.8/100 PY in 2017-2018. The highest reinfection rates were observed among those treated in prison (14.3/100 PY) and community settings (9.5/100 PY). Among those treated in the DAA era (2015-2018), 68% were tested within the first year post-SVR but only 30% in the second year; while 169 reinfections were diagnosed in follow-up, an estimated 200 reinfections (54% of the estimated total) had gone undetected.ConclusionsHCV reinfection rates among PWID in Scotland have risen alongside the scale-up of DAAs and broadened access to treatment for those at highest risk, through delivery in community drug services. Promotion of HCV testing post-SVR among PWID is essential to ensure those reinfected are identified and retreated promptly.Lay summaryIncreased rates of hepatitis C reinfection in Scotland were observed following the rapid scale-up of highly effective direct-acting antiviral (DAA) treatments among people who inject drugs. This demonstrates that community-based treatment pathways are reaching high-risk groups, regarded vital in efforts to eliminate the virus. However, we estimate that less than half of reinfections have been detected in the DAA era because of inadequate levels of retesting beyond the first year following successful treatment. Sustained efforts that involve high coverage of harm reduction measures and high uptake of annual testing are required to ensure prompt diagnosis and treatment of those reinfected if the goals of elimination are to be met.