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The hepatitis C virus (HCV) prevalence is extremely high in patients who consume and inject illicit drugs. Concerns about poor adherence and fear of interaction with drugs of abuse could constitute further disincentive for treatment initiation in these patients. We discussed the pharmacokinetics (PKs) and pharmacodynamics (PD) of currently prescribed direct antiviral agents (NSA5 inhibitors: daclatasvir, elbasvir, ledipasvir, pibrentasvir, velpatasvir; NS5B inhibitor: sofosbuvir; NS3/4A protease inhibitors: glecaprevir, grazoprevir, voxilaprevir) and most common substances of abuse (opioids: buprenorphine, fentanyl, heroin, methadone, morphine, oxycodone; stimulants: amphetamines, cathinones, cocaine; cannabinoids; ethanol). Overall, most direct-acting antivirals (DAAs) are substrates and inhibitors of the transmembrane transporter P-glycoprotein (P-gp), and several of them are metabolized by cytochrome P450 enzymes. Clinically relevant interactions are associated with P-gp and CYP3A modulators. Most substances of abuse are eliminated by Phase I and Phase II metabolizing enzymes, but none of them are either major inhibitors or inducers. PK studies did not show any relevant interactions between DAA and methadone or buprenorphine. Based on pharmacological considerations, neither efficacy loss nor adverse drug event associated with detrimental interaction are expected with opioids, stimulants, cannabinoids and ethanol. In summary, our literature review shows that the interaction potential of DAA with most opioids and illicit drugs is limited and should not be a hurdle to the initiate DAA., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Hepatitis C virus (HCV) among people living in detention (PLD) is typically high in many countries including Switzerland, where it is estimated that the HCV prevalence rate is between 5.7% and 6.2%. In Switzerland, the existing screening strategy involves routine screening of PLD who indicate they are from HCV high-risk populations based on questionnaire responses upon entry to the detention center, rather than an offer to screen all PLD., Methods: A cost-effectiveness analysis from a Swiss healthcare provider perspective was conducted by combining a 5-year decision tree screening model with results from a Markov model of HCV treatment outcomes. This model explored the cost-effectiveness of increased HCV screening to cover all PLD compared to the current approach, using a standard test package and subsequent treatment with a single-tablet regimen in Swiss custodial settings. Sensitivity and scenario analyses examined the uncertainty of results., Results: At the willingness-to-pay threshold of 100 000 Swiss Francs (CHF) per quality-adjusted life-year (QALY), comprehensive general screening was cost-effective compared to current risk-based screening, with a base case incremental cost-effectiveness ratio of CHF 14 312 per QALY. The net monetary benefit of screening the whole PLD population was CHF 23 298 046 and CHF 4298 per person. The proportion of PLD tested was predicted to increase from 13.6% to 67.0% under comprehensive screening., Conclusion: The results showed that comprehensive screening strategies in detention centers in Switzerland can be cost-effective, with the probabilistic sensitivity analysis estimating an 82.3% probability of cost-effectiveness., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objective: We aimed to determine the association between the stepwise increase in the sustained viral response (SVR) and Swiss and United States (US) market prices of drug regimens for treatment-naive, genotype 1 chronic hepatitis C virus (HCV) infection in the last 25 years. We identified the following five steps in the development of HCV treatment regimens: 1) interferon (IFN)-α monotherapy in the early '90s, 2) IFN-α in combination with ribavirin (RBV), 3) pegylated (peg) IFN-α in combination with RBV, 4) the first direct acting antivirals (DAAs) (telaprevir and boceprevir) in combination with pegIFN-α and RBV, and 5) newer DAA-based regimens, such as sofosbuvir (which is or is not combined with ledipasvir) and fixed-dose combination of ritonavir-boosted paritaprevir and ombitasvir in combination with dasabuvir., Design: We performed a linear regression and mean cost analysis to test for an association between SVRs and HCV regimen prices. We conducted a sensitivity analysis using US prices at the time of US drug licensing. We selected randomized clinical trials of drugs approved for use in Switzerland from 1997 to July 2015 including treatment-naïve patients with HCV genotype 1 infection., Results: We identified a statistically significant positive relationship between the proportion of patients achieving SVRs and the costs of HCV regimens in Switzerland (with a bivariate ordinary least square regression yielding an R2 measure of 0.96) and the US (R2 = 0.95). The incremental cost per additional percentage of SVR was 597.14 USD in Switzerland and 1,063.81 USD in the US., Conclusion: The pricing of drugs for HCV regimens follows a value-based model, which has a stable ratio of costs per achieved SVR over 25 years. Health care systems are struggling with the high resource use of these new agents despite their obvious long-term advantages for the overall health of the population. Therefore, the pharmaceutical industry, health care payers and other stakeholders are challenged with finding new drug pricing schemes to treat the entire population infected with HCV.

New direct-acting antivirals (DAA) against hepatitis C virus (HCV) have led to a therapeutic revolution in HCV management and virological cure rates approaching 100% while potentially avoiding significant complications of HCV (first cause of liver transplantation). We estimated the price of sustained virological response (SVR) depending on treatment strategy and patient profile. Costs of treatment with recent DAAs being so high, the accessibility to those drugs for the majority of subjects is hitherto limited to advanced stages of hepatitis C. This current situation increases the inequity and strengthens the dominant position of insurers and pharmaceutical companies with a rationing of care. We suggest herein global approaches from a population-level and health-care perspective aiming to reduce the prevalence, morbidity, and mortality related to HCV.