Hepatitis C Virus Treatment Options Research Articles

Country versus pharmaceutical company interests for hepatitis C treatment.

Hepatitis C virus (HCV) is one of the leading causes of liver disease and is responsible for massive health and economic burden worldwide. The disease is asymptomatic in its early stages, but it can progress over time to fatal end-stage liver disease. Thus, the majority of individuals infected with HCV are unaware of their chronic condition. Recent treatment options for HCV can completely cure the infection but are costly. We developed a game model between a pharmaceutical company (PC) and a country striving to maximize its citizens' utility. First, the PC determines the price of HCV treatment; then, the country responds with corresponding screening and treatment strategies. We employed an analytical framework to calculate the utility of the players for each selected strategy. Calibrated to detailed HCV data from Israel, we found that the PC will gain higher revenue by offering a quantity discount rather than using standard fixed pricing per treatment, by indirectly forcing the country to conduct more screening than it desired. By contrast, risk-sharing agreements, in which the country pays only for successful treatments are beneficial for the country. Our findings underscore that policy makers worldwide should prudently consider recent offers by PCs to increase screening either directly, via covering HCV screening, or indirectly, by providing discounts following a predetermined volume of sales. More broadly, our approach is applicable in other healthcare settings where screening is essential to determine treatment strategies.

The Knowledge on HCV: From the Discovery to the Elimination

AbstractFrom being described as “non-A, non-B” hepatitis in 1975 and being identified in 1989, to the emergence of direct-acting antiviral drugs (DAAs), knowledge on hepatitis C virus (HCV) has achieved a qualitative leap in recent decades. Although more than 95% of HCV patients can be cured by DAAs, the high detection rate, high treatment cost, and relative high recurrence rate for some subtypes (eg, type 3b) make it still a public health problem worldwide. Due to the widespread availability of DAAs, vaccine research has received relatively little attention. The purpose of this review is to look back to the discovery of the HCV, its life cycle, innate and adaptive immune responses, and the evolution of treatment options for HCV.

The impact of genetic variations in sofosbuvir metabolizing enzymes and innate immunity mediators on treatment outcome in HCV-infected patients

Hepatitis C virus (HCV) is the leading cause of liver diseases worldwide. At present, combinations of different classes of direct-acting antiviral agents (DAAs) are used as treatment options for HCV, in which sofosbuvir (SOF) is the common DAA among different therapeutic regimes. In Egypt, SOF plus daclatasvir (DCV) is the widely used anti-HCV treatment protocol. Herein, we aimed to assess the association between 3 single-nucleotide polymorphisms (SNPs) at the genes coding for 2 SOF metabolizing enzymes: histidine triad nucleotide-binding protein 1 (HINT1) rs4696/rs7728773 and nucleoside diphosphate kinase 1 (NME1) rs3760468, together with the most potent anti-HCV innate molecule, i.e., interferon lambda 3 (IFNL3) rs12979860 and the response to SOF/DCV in Egyptian patients chronically infected with genotype 4 (GT4). SNPs were genotyped using real-time PCR in DNA from patients who achieved sustained virological response (SVR) at 12 weeks post-SOF/DCV treatment (i.e., responders; n = 188), patients who failed to achieve SVR12 (i.e., non-responders; n = 109), and healthy controls (n = 62). Our results demonstrated that patients bearing HINT1 rs7728773 CT/TT (odds ratio 2.119, 95% CI 1.263–3.559, p = 0.005) and IFNL3 rs12979860 CC (odds ratio 3.995, 95% CI 2.126–7.740, p = 0.0001) were more likely to achieve SVR12. However, neither HINT1 rs4696 nor NME1 rs3760468 seems to contribute to the responsiveness to SOF/DCV. Binary regression analysis defined 5 predictor factors independently associated with SVR12: age, bilirubin, hemoglobin, early stages of fibrosis, and combined HINT1 rs7728773 and IFNL3 rs12979860 favorable and mixed genotypes (odds ratio 3.134, 95% CI 1.518–6.47, p = 0.002), and that was confirmed by the combined ROC curve for the 5 predictor factors (AUC = 0.91, 95% CI 0.869–0.95, P = 0.0001). In conclusion, these data suggest that the two SNPs have the potential in predicting the response rate to SOF/DCV treatment in patients infected with HCV GT4. This study is the first to investigate the pharmacogenetics of SOF metabolizing enzyme and introduce HINT1 rs7728773 as a novel SNP that predicts the treatment efficacy.

Country versus Pharmaceutical Company Interests for Hepatitis C Elimination

Hepatitis C virus (HCV) is one of the leading causes of liver disease, and responsible for massive health and economic burden worldwide. In its early stages, the disease is asymptomatic, but it can progress over time to fatal end-stage liver disease. Thus, the majority of individuals infected with HCV are unaware of their chronic condition. Recent treatment options for HCV can completely cure the infection but are costly. We developed a game model between a pharmaceutical company (PC) and a country striving to maximize the utility of its citizens. First, the PC determines the price of HCV treatment; then, the country responds with corresponding screening and treatment strategies. We employed an analytical framework to calculate the utility of the players for each selected strategy. Calibrated to detailed HCV data, we found that the PC will gain higher revenue by offering a quantity discount rather than using standard linear pricing, by indirectly forcing the country to conduct more screening than it desires. We also present several strategies to substantially mitigate this sub-optimal outcome for the country. Thus, policy makers worldwide should prudently consider recent offers by PCs to increase screening either directly, via covering HCV screening, or indirectly, by providing discounts following a predetermined volume of sales. Our approach provides a rational explanation for the current agreements between countries and PCs. It is applicable in other healthcare settings where screening is essential to determine treatment strategies.

Drug Resistance in Hepatitis C Virus: Future Prospects and Strategies to Combat It.

Induction of highly pathogenic hepatitis C virus (HCV) causes chronic hepatitis round the world. This virus is easily prone to developing resistance against antiviral drugs because of two viral polymerases that do not possess the proofreading and overlapping reading frame abilities. There is more than one explanation for how this virus builds up resistance against antiviral drug treatments. Assays are now available to detect HCV-resistant variants, based on phenotypic and genotypic assays, and next generation sequencing. But these assays are of a little value at baseline, because they are not influential enough for making therapeutic decisions in HCV patients. Moreover, HCV monitoring is now an essential part of clinical practice. Special patients, such as those with thalassemia, renal transplant due to renal failure, and the patients undergoing hemodialysis, are at higher risk for acquiring this infection. Management of HCV infection in these patient groups is complicated by multiple side effects, including flu-like symptoms, neutropenia, fever, and neuropsychiatric disorders, thus limiting the use of ribavirin and coexisting iron overload. In HCV patients suffering from depression, the treatment may be discontinued because of some defects in neurochemical pathways caused by interferon, which can enhance the level of depression in these patients. In addition, obesity has been found to be a marker of failure of HCV treatment. There will be many resistance tolerant HCV treatment options available in the near future.

Glecaprevir/Pibrentasvir: The First 8-Week, Pangenotypic HCV Treatment Regimen for Patients 12 Years of Age and Older.

Objective: To review the pharmacology, pharmacokinetics, efficacy, safety, dosing, and cost information of glecaprevir/pibrentasvir in the treatment of hepatitis C virus (HCV). Data Sources: A literature search was conducted between September 2018 and July 2019 using PubMed and Google Scholar with the search terms glecaprevir, pibrentasvir, Mavyret, Maviret, and hepatitis C. Clinicaltrials.gov was searched using the same terms. References of published articles were assessed for additional information. Study Selection and Data Extraction: English-language preclinical and clinical studies on the chemistry, pharmacology, pharmacokinetics, safety, and efficacy of glecaprevir/pibrentasvir were evaluated. Data Synthesis: Food and Drug Administration-approved glecaprevir/pibrentasvir is considered both safe and efficacious for the treatment of HCV genotypes 1 to 6 and in several patient populations, such as those with treatment-naïve or treatment-experienced HCV; with or without compensated cirrhosis, HIV-1 coinfection, or renal impairment; post-liver or post-kidney transplant; and ≥12 years of age. Sustained virological response rates ranged from 83% to 100% in clinical trials, and safety outcomes appear similar to other guideline-recommended HCV treatment options. Relevance to Patient Care and Clinical Practice: This review discusses the pharmacological, efficacy, and safety data found in glecaprevir/pibrentasvir clinical trials and relates this to guideline recommendations and the practical use of this medication for treatment of HCV. Conclusions: With HCV infection rates remaining elevated, it is important to have safe and efficacious treatment options. Glecaprevir/pibrentasvir is a safe and efficacious guideline-recommended, 8-week treatment for HCV in several patient populations, with these populations likely growing in the near future given ongoing and future studies.

Promoting treatment for hepatitis C in people who inject drugs: A review of the barriers and opportunities.

People who inject drugs (PWIDs) comprise a significant amount of the population who are also positive for hepatitis C virus (HCV) around the world. Even though there is evidence that patients who currently inject drugs do not display altered treatment adherence or medication effectiveness, health care providers are still hesitant to treat this patient population based on perceived threats and barriers. This literature review informs of the perceived barriers associated with PWID in receiving HCV treatment and supports recommendations to address these barriers. For this review, eight scholarly articles rated levels I A through II B using John Hopkins Evidence-Based Practicing ratings consisting of randomized controlled trials, systematic reviews, and meta-analyses were selected. Both qualitative and quantitative data contributed to identifying perceived barriers and suggested course of action that should be taken to increase HCV treatment uptake among PWID. The three main perceived barriers are evidence of barriers to treatment in the PWID populations and include increased risk of reinfection, low adherence to treatment, and decreased response to treatment. Removal of these barriers by increasing education about HCV disease and treatment options to both patients and health care workers and changing current policy in health care settings to provide enhanced access to HCV treatment for PWID can promote an opportunity for successful treatment of these patients. There is a significant need for HCV treatment among PWID. Opportunities for successful treatment exist and should be adopted.

A Success Story: Advances in Treatment and Lower Disease Prevalence of Hepatitis C Has a Large Impact on Medical Plan Costs.

The aim of this study was to evaluate medical and pharmaceutical costs and health outcomes among commercially insured members treated for hepatitis C virus (HCV) infections from a large, academic institution. Data are derived from the University of Texas System (UT SELECT) medical and pharmacy claims database. This study is a retrospective claims analysis of secondary, deidentified data from 2006 to 2016. The number of HCV-infected and treated patients decreased from 22.5 per 10,000 members in 2006 to 0.15 per 10,000 members in 2016 (P < 0.0001). Medical and pharmacy paid per member per month (PMPM) costs were highest among HCV-infected members with advanced liver disease (total paid PMPM = $2737, medical PMPM = $1537, pharmacy PMPM = $1200). The declining prevalence of acute HCV infections and the introduction of efficacious HCV treatment options for chronic HCV in this commercial population have resulted in significant reductions in HCV-related medical claims and the clinical sequelae of advanced liver diseases. Although HCV treatment to achieve sustained viral response remains expensive, the prevention of advanced liver disease decreased system-wide medical costs for this insured population.

A pan-genotypic Hepatitis C Virus NS5A amplification method for reliable genotyping and resistance testing

BackgroundChronic infection with the Hepatitis C Virus (HCV) is associated with the risk of progressive liver disease. Although, HCV treatment options and viral cure rates have tremendously increased over the last decade, all currently licensed combination therapies contain inhibitors of the replication complex NS5A. Resistance-associated substitutions (RAS) in NS5A can limit the efficacy of therapy; however, resistance testing is routinely not recommended for all patients. Notably, pan-genotypic combinations have been approved, however the correct identification of the HCV genotype is still required for treatment decisions and is a good predictor for treatment success. ObjectiveThe aim of this study was the establishment of a pan-genotypic NS5A amplification method for reliable genotyping and simultaneous resistance testing in a fast and cheap routine diagnostic setup. Study designPan-genotypic degenerated nested PCR primer were designed and tested in 262 HCV-patients. The collection included samples from genotypes 1–7 and the median viral load was 1.07 × 106 IU/ml (range 248-21 × 106 IU/ml). ResultsAmplification of the expected 747bp fragment was successful in 257 of 262 (98.1%) samples including samples <1000 IU/ml. The direct comparison of the genotype information obtained with core sequencing to those obtained by NS5A prediction showed high concordance (97.3%) and discrepancies occurred only for relatively rare subtypes. Resistance analysis using Geno2Pheno[HCV] showed NS5A-RAS in 23 of 257 (8.9%) of samples. ConclusionsWe successfully developed a routine diagnostic method for pan-genotypic amplification of NS5A. This amplicon can be used for simultaneous genotyping and resistance testing for enhancing and improving routine HCV diagnostic.

Hepatitis C virus infection among people who inject drugs in Bangkok, Thailand, 2005-2010.

Approximately 1% of adults in Thailand are infected with hepatitis C virus (HCV). New direct-acting antiviral agents achieve sustained virologic responses in >95% of HCV-infected patients and are becoming available in countries around the world. To prepare for new HCV treatment options in Thailand, this study characterized HCV infections among people who inject drugs (PWID) in Bangkok. The Bangkok Tenofovir Study (BTS) was a pre-exposure prophylaxis trial conducted among PWID, 2005-2013. Blood specimens were randomly selected from PWID screened for the BTS, to test for anti-HCV antibody and HCV RNA. The HVR1 region was amplified by polymerase chain reaction, using multiplex primer sets with unique identifier sequences; amplification products were pooled in sets of 25; and consensus sequencing was performed to characterize individual HCV genotypes. The median age of 3679 participants tested for anti-HCV antibody was 31 years, 3016 (82.0%) were male and 447 (12.2%) were HIV infected. The prevalence of anti-HCV antibody was 44.3%. The adjusted odds of testing positive for anti-HCV antibody were higher in men (adjusted odds ratio [aOR] 3.2, 95% confidence interval [CI] 2.4-4.3), those aged 40 years or older (aOR 2.7, 95% CI 2.1-3.5), those who had more than a primary school education (aOR 1.7, 95% CI 1.4-2.1), and those who tested HIV positive (aOR 5.2, 95% CI 3.7-7.4). HCV RNA was detected in 644 (81.3%) of the 792 anti-HCV antibody-positive specimens, yielding an HCV RNA-positive prevalence of 36.0% (95% CI 33.8-38.2). Among a random sample of 249 of the 644 specimens, 218 could be characterized, and the most common HCV subtypes were 1a (30.3%), 1b (12.8%), 3a (35.8%), 3b (6.9%) and 6n (8.7%). The prevalence of anti-HCV antibody among PWID was 44.3% and more than one third (36.0%) were HCV RNA positive. Genotypes 1, 3 and 6 accounted for all typable infections. As the government of Thailand considers introduction of direct-acting antiviral medications for people with hepatitis C, it will be important to ensure that the medications target these subtypes.

Drug consumption rooms (DCRs) as a setting to address hepatitis C \u2013 findings from an international online survey

BackgroundPrevalence of Hepatitis C Virus (HCV) among people who inject drugs (PWID) is high. Risky injecting behaviours have been found to decrease in drug consumption rooms (DCRs) and supervised injecting facilities (SIFs), yet HCV prevention and treatment in these settings have not been extensively explored.MethodsTo determine the range and scope of HCV prevention and treatment options in these services, we assessed DCR/SIF operational features, their clients’ characteristics and the HCV-related services they provide. A comprehensive online survey was sent to the managers of the 91 DCRs/SIFs that were operating globally as of September 2016. A descriptive cross-country analysis of the main DCR/SIF characteristics was conducted and bivariate logistic models were used to assess factors associated with enhanced HCV service provision.ResultsForty-nine valid responses were retrieved from DCRs/SIFs in all countries where they were established at the time of the survey (Australia, Canada, Denmark, France, Germany, Luxembourg, Netherlands, Norway, Spain and Switzerland). Internationally, the operational capacities of DCRs/SIFs varied in terms of funding, location, size and staffing, but their clients all shared common features of vulnerability and marginalisation. Estimated HCV prevalence rates were around 60%. Among a range of health and social services and referrals to other programs, most DCRs/SIFs provided HCV testing onsite (65%) and/or offered liver monitoring or disease management (54%). HCV treatment onsite was offered or was planned to be offered by 21% of DCRs/SIFs. HCV testing onsite was associated with provision of other services addressing blood-borne diseases and HCV treatment was linked to the provision of OST. HCV disease management was associated with employing a nurse at a DCR/SIF and HCV treatment was associated with employing a medical doctor.ConclusionsDCRs/SIFs offer easy-to-access HCV-related services for PWID. The availability of onsite medical professionals and provision of support and education to non-medical staff are key to enhanced provision of HCV-related services in DCRs/SIFs. Funding and support for HCV treatment at the community level, via low-threshold services such as DCRs/SIFs, are worthy of action.

Project HELP: a study protocol to pilot test a shared decision-making tool about treatment options for patients with hepatitis C and chronic kidney disease

BackgroundRecent advances in treatment have given patients with chronic kidney disease (CKD) access to safer and more effective medications to treat comorbid hepatitis C virus (HCV) infection. Given the variety and complexity of treatment options that depend on patients’ clinical characteristics and personal preferences, education and decision support are needed to prepare patients better to discuss treatment options with their clinicians.MethodsDrawing on International Patient Decision Aids Standards guidelines, literature reviews, and guidance from a diverse expert advisory group of nephrologists, hepatologists, and patients, we will develop and test a HCV and CKD decision support tool. Named Project HELP (Helping Empower Liver and kidney Patients), this tool will support patients with HCV and CKD during decisions about whether, when, and how to treat each illness. The tool will (1) explain information using plain language and graphics; (2) provide a step-by-step process for thinking about treating HCV and CKD; (3) tailor relevant information to each user by asking about the individual’s stage of CKD, stage of fibrosis, prior treatment, and comorbidities; (4) assess user knowledge and values for treatment choices; and (5) help individuals use and consider information appropriate to their values and needs to discuss with a clinician. A pilot study including 70 individuals will evaluate the tool’s efficacy, usability, and likelihood of using it in clinical practice. Eligibility criteria will include individuals who understand and read English, who are at least 18 years old, have a diagnosis of HCV (any genotype) and CKD (any stage), and are considering treatment options.DiscussionThis study can identify particular characteristics of individuals or groups that might experience challenges initiating treatment for HCV in the CKD population. This tool could provide a resource to facilitate patient-clinician discussions regarding HCV and CKD treatment options.

Efficient care delivery of effective hepatitis C virus treatments in Medicaid beneficiaries without cirrhosis

The hepatitis C virus (HCV) targets the liver and increases the chance of negative liver-related health outcomes. The recent wave of direct-acting antiviral (DAA) treatments is highly effective, with reduced side effects compared to prevailing options, and is recommended by the American Association for the Study of Liver Disease–Infectious Diseases Association (AASLD–IDSA), as of June 2017. In the administration of DAA treatment in Medicaid, however, patients with cirrhosis have been given priority. The extent of efficiency and cost savings associated with delivery of treatments in patients without cirrhosis is in question. The aim of this study was to analyse the efficiency of HCV treatment options and practice recommendations in Medicaid beneficiaries as a national cohort. To quantitatively evaluate treatment efficiency, treatments recommended by AASLD–IDSA were modelled using inputs from the published literature and the Medicaid National Average Drug Acquisition Cost. For modelled patients, ombitasvir/paritaprevir/ritonavir/dasabuvir/ribavirin would be the preferred, most efficient and effective treatment for Medicaid. Despite real world variation in treatment discontinuation, DAA treatment results in savings for Medicaid. The results suggest that DAA regimens as a first line of treatment is both an effective and an efficient practice in patients without cirrhosis, reducing all-cause health-care costs, preventing disease stage progression and averting morbidity.

Efficacy and Safety of Elbasvir/Grazoprevir in Patients with Chronic Hepatitis C Virus Infection and Inherited Blood Disorders: Final Data from the C-Edge Ibld Study

Efficacy and Safety of Elbasvir/Grazoprevir in Patients with Chronic Hepatitis C Virus Infection and Inherited Blood Disorders: Final Data from the C-Edge Ibld Study

Reinventing HCV Treatment: Past and Future Perspectives

This review paper summarizes the epidemiology of hepatitis C virus (HCV) and chronic HCV infection, including HCV virology and treatment regimens. Specifically, we focus on the evolution of past, current, and future HCV treatment options, the reasons for treatment failure, and the impact of resistance-associated variants on treatment success.

Use of network meta-analysis in clinical guidelines.

The World Health Organization (WHO) has conducted two major updates to global guidance for the management of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections in 2016. (1,2) Recommendations made by WHO can have an important effect on policy and practice, particularly for low- and middle-income countries. For instance, a 2014 survey found that over three-quarters of all 158 recommendations for HIV and tuberculosis were incorporated into national guidelines. (3) Clinical guidelines are developed through multi-step processes that ensure that guidelines are feasible within the current clinical environment and that they are based on the best available evidence. For the latest HIV and HCV guidelines, WHO used network meta-analysis to inform treatment recommendations. An expansion of conventional pairwise meta-analysis, network meta-analysis includes multiple interventions within a single analysis and estimates the relative treatment effect between each two treatments compared using direct or indirect evidence. Although it is often acknowledged that having the most up-to-date evidence is critical to the development of clinical guidelines, it is equally important that the optimal analytical methods are used to appraise the evidence. We explain here why network meta-analysis lends itself to the development of clinical guidelines and why it may be used more often in this context. WHO has a history of improving the methods it uses for developing its guidelines. Following calls for greater transparency in the use of evidence for decision-making, (4) WHO adopted a process for guideline development in 2007 that included the use of the GRADE approach (grading of recommendations, assessment, development and evaluation) to support decision-making. In addition to clinical evidence, WHO guideline groups take account of factors such as patient preferences, feasibility, costs and human rights. (5) To support decision-making beyond clinical effectiveness, mathematical models have been used to appraise the cost-effectiveness and epidemiological impact of HIV testing and treatment strategies in 2013. (6) WHO guidelines are regularly revised, generally every 3-5 years, to provide up-to-date guidance on interventions to contain or reduce major public health threats. With an ever-growing number of treatment options for HIV and HCV, methods used to synthesize the evidence within the guideline development procedures should maximize the use of all evidence and generate results that can be translated into recommendations. Although the use of network meta-analysis for WHO guideline development is recent, the method is well established within national health technology assessment agencies. It has become essential to formulating recommendations on reimbursements by health care agencies around the world. The method has also recently been adopted by Cochrane, and we found that since 2015, 10% (23/230) of systematic reviews published by this organization used network meta-analysis. The method has numerous qualities that lend themselves to decision-making processes such as clinical guidelines development. In 2015, GRADE working groups published guidance on how to use GRADE in conjunction with network meta-analysis. (7) Furthermore, the National Institute for Health and Clinical Excellence (NICE) in the United Kingdom of Great Britain and Northern Ireland has included recommendations on network meta-analysis within its clinical guidelines manual. (8) However, in 2012 only 8% of 138 NICE clinical guidelines had used network meta-analysis, (9) but the percentage is likely to be higher today. Systematic evidence appraisal, but not the network meta-analysis approach, was used to formulate recommendations in other recent, major guidelines for HIV and HCV disease. (10-12) Network meta-analysis offers several advantages to the process of developing guidelines. One advantage is the ability to make a quantitative comparison of interventions that have not been directly compared in studies. …

Treatment of severe recurrent hepatitis C after liver transplantation in HIV infected patients using sofosbuvir-based therapy.

For liver transplant recipients with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection, recurrence after LT is associated with a higher risk of graft loss than for HCV mono-infected patients. Prior HCV treatment options were limited by side effects and drug-drug interactions. To evaluate treatment outcomes with sofosbuvir (SOF)-based therapy among HIV/HCV coinfected liver transplant recipients. Access to SOF and ribavirin (RBV) prior to regulatory approval was attained via an international compassionate access program for transplant recipients with a life expectancy of 1 year or less in the absence of HCV treatment. This report focuses on the short and longer term outcomes in HCV-HIV co-infected liver transplant recipients. Twenty patients were treated, nine with early severe recurrence and 11 with cirrhosis. Eleven patients received SOF and RBV, one SOF, RBV and Peg-interferon, three SOF, RBV and simeprevir and five SOF, RBV and daclatasvir. Of the 18 patients who completed treatment, 16 (89%) achieved sustained virological response 12 weeks after the end of treatment (SVR12). Liver function tests (including bilirubin and albumin) improved significantly over time. Nineteen serious adverse events occurred in eight (40%) patients, none of them related to SOF. Two patients died during treatment and another, 1 year after the end of therapy, due to progressive end-stage liver disease. Importantly, HIV suppression was not compromised. No significant drug-drug interactions were reported. Sofosbuvir-based regimens are safe, well-tolerated and provide high rates of SVR in HCV-HIV co-infected patients with severe recurrence after-liver transplant.

The hepatitis C treatment revolution: how to avoid Asia missing out

The Asia-Pacific region bears a high burden of hepatitis C virus (HCV) infections and the largest number of global deaths. Populations most at risk of infection and disease progression include people who inject drugs and those living with HIV. HCV treatment options have rapidly expanded in the past few years through the development of direct-acting antiviral (DAA) medicines, which can cure HCV in over 95% of cases, but are prohibitively expensive. While price is the major barrier to treatment access, voluntary licensing has resulted in limited availability of one DAA (sofosbuvir) through generic manufacturers in India. Regulatory barriers, such as the need for domestic clinical trials, cause further delays in local medicines approvals and access.Intensive advocacy by civil society in combination with mobilisation of global resources for HIV treatment were critical to achieving price reductions in HIV medicines in the early 2000s. While the current global economic situation is less conducive to substantial funding support for HCV treatment, community advocates are building awareness of the growing opportunities for HCV cure. Key immediate steps include the inclusion of DAAs in domestic essential medicines lists, as the World Health Organization has already done for globally, and fast-tracking domestic drug approvals to facilitate government-level price negotiations with originator and generic pharmaceutical companies. Urgent action by a broad range of stakeholders is needed to facilitate access to HCV treatment in order to ensure that the millions of people living with hepatitis C in the Asia-Pacific will not miss out on these life-saving treatments.

VRNA structured population model for Hepatitis C Virus dynamics

Improvements in the understanding of the Hepatitis C Virus (HCV) life-cycle have led to the identification of targets and the development of drugs affecting the intracellular reproduction of the virus. These advancements have presented new modeling challenges as the classic models have focused on describing the macroscopic viral kinetics only. Our primary objective is to apply the existing theory of Physiologically Structured Population (PSP) modeling to describe dynamics of viral RNA (vRNA) in infected hepatocytes of patients receiving treatment with Direct-acting Antiviral Agents (DAA). Using vRNA as a physiological structure this work expands on previous structured population models allowing exploration of micro- and macroscopic implications of such treatments. The PSP model provides a description of vRNA distribution in the infected cells at steady state and its time evolution following treatment. The long term behavior of the model predicts viral load time courses in plasma and permits to quantify conditions for the virus eradication. Finally, we demonstrate that PSP models can account for additional structures, which are essential for the viral replication process with potentially far reaching implications in our understanding of HCV infections and treatment options.

HIV and HCV Medications in End-Stage Renal Disease.

Human immunodeficiency virus (HIV) infection and hepatitis C virus (HCV) infection affect populations worldwide. With the availability of over 35 Food and Drug Administration approved medications for treatment of HIV, the morbidity and mortality associated with HIV has greatly improved. On the other hand, treatment options for HCV have been limited until very recently. While the use of protease inhibitors (such as boceprevir and telaprevir) has become standard of care for treatment of hepatitis C in the general population, data for individuals with impaired kidney function, particularly those on dialysis, are extremely limited. Use of medications in dialysis patients can be challenging given the dose adjustments that must be made for renally cleared molecules, and potentially increased impact of adverse effects such as anemia. Recommendations for dosing of marketed therapies for HIV and HCV are reviewed.