COVID-19 Treatments Sold Online Without Prescription Requirements in the United States: Cross-sectional Study Evaluating Availability, Safety and Marketing of Medications.

BACKGROUND: The COVID-19 pandemic has increased online purchases and heightened interest in existing treatments. Dexamethasone, hydroxychloroquine, and lopinavir-ritonavir have been touted as potential COVID-19 treatments. OBJECTIVE: This study assessed the availability of 3 potential COVID-19 treatments online and evaluated the safety and marketing characteristics of websites selling these products during the pandemic. METHODS: A cross-sectional study was conducted in the months of June 2020 to August 2020, by searching the first 100 results on Google, Bing, and Yahoo! mimicking a US consumer. Unique websites were included if they sold targeted medicines, were in English, offered US shipping, and were free to access. Identified online pharmacies were categorized as rogue, unclassified, or legitimate based on LegitScript classifications. Patient safety characteristics, marketing techniques, price, legitimacy, IP addresses, and COVID-19 mentions were recorded. RESULTS: We found 117 websites: 30 selling dexamethasone (19/30, 63% rogue), 39 selling hydroxychloroquine (22/39, 56% rogue), and 48 selling lopinavir-ritonavir (33/48, 69% rogue). This included 89 unique online pharmacies: 70% were rogue (n=62), 22% were unapproved (n=20), and 8% were considered legitimate (n=7). Prescriptions were not required among 100% (19/19), 61% (20/33), and 50% (11/22) of rogue websites selling dexamethasone, lopinavir-ritonavir, and hydroxychloroquine, respectively. Overall, only 32% (24/74) of rogue websites required prescriptions to buy these medications compared with 94% (31/33) of unapproved and 100% (10/10) of legitimate websites (P<.001). Rogue sites rarely offered pharmacist counseling (1/33, 3% for lopinavir-ritonavir to 2/22, 9% for hydroxychloroquine). Drug warnings were unavailable in 86% (6/7) of unapproved dexamethasone sites. It was difficult to distinguish between rogue, unapproved, and legitimate online pharmacies solely based on website marketing characteristics. Illegitimate pharmacies were more likely to offer bulk discounts and claim price discounts, yet dexamethasone and hydroxychloroquine were more expensive online. An inexpensive generic version of lopinavir-ritonavir that is not authorized for use in the United States was available online offering US shipping. Some websites claimed hydroxychloroquine and lopinavir-ritonavir were effective COVID-19 treatments despite lack of scientific evidence. In comparing IP addresses to locations claimed on the websites, only 8.5% (7/82) matched their claimed locations. CONCLUSIONS: The lack of safety measures by illegitimate online pharmacies endanger patients, facilitating access to medications without appropriate oversight by health care providers to monitor clinical response, drug interactions, and adverse effects. We demonstrated how easy it is to go online to buy medications that are touted to treat COVID-19 even when current clinical evidence does not support their use for self-treatment. We documented that illegitimate online pharmacies sidestep prescription requirements, skirt pharmacist counseling, and make false claims regarding efficacy for COVID-19 treatment. Health care professionals must urgently educate the public of the dangers of purchasing drugs from illegitimate websites and highlight the importance of seeking treatment through authentic avenues of care.

Non-epidemic HCV genotypes in low- and middle-income countries and the risk of resistance to current direct-acting antiviral regimens.

The hepatitis C virus (HCV) is an extremely diverse virus, subtypes of which are distributed variably around the world. Viral genotypes may be divided into epidemic subtypes; those that have become prevalent globally, and endemic subtypes that have a more limited distribution, mainly in Africa and Asia. The high variability of endemic strains reflects evolutionary origins in the locations where they are found. This increased genetic diversity raises the possibility of resistance to pan-genotypic direct-acting antiviral regimens. While many endemic subtypes respond well to direct-acting antiviral therapies, others, for example genotypes 1l, 3b and 4r, do not respond as well as predicted. Many genotypes that are rare in high-income countries but common in other parts of the world have not yet been fully assessed in clinical trials. Further sequencing and clinical studies in sub-Saharan Africa and Asia are indicated to monitor response to treatment and to facilitate the World Health Organization's 2030 elimination strategy.

Impact of direct-acting antivirals for HCV on mortality in a large population-based cohort study.

BACKGROUND & AIMS: We evaluated the effect of direct-acting antiviral (DAA)-induced sustained virologic response (SVR) on all-cause, liver- and drug-related mortality in a population-based cohort in British Columbia, Canada. METHODS: We used data from the British Columbia Hepatitis Testers Cohort, which includes people tested for HCV since 1990, linked with data on medical visits, hospitalizations, prescription drugs and mortality. We followed people who received DAAs and people who did not receive any HCV treatment to death or December 31, 2019. We used inverse probability of treatment weighting to balance the baseline profile of treated and untreated individuals and performed multivariable proportional hazard modelling to assess the effect of DAAs on mortality. RESULTS: Our cohort comprised 10,851 people treated with DAAs (SVR 10,426 [96%], no-SVR: 425) and 10,851 matched untreated individuals. Median follow-up time was 2.2 years (IQR 1.3-3.6; maximum 6.2). The all-cause mortality rate was 19.5/1,000 person-years (PY) among the SVR group (deaths = 552), 86.5/1,000 PY among the no-SVR group (deaths = 96), and 99.2/1,000 PY among the untreated group (deaths = 2,133). In the multivariable model, SVR was associated with significant reduction in all-cause (adjusted hazard ratio [aHR] 0.19; 95% CI 0.17-0.21), liver- (adjusted subdistribution HR [asHR] 0.22, 95% CI 0.18-0.27) and drug-related mortality (asHR 0.26, 95% CI 0.21-0.32) compared to no-treatment. Older age and cirrhosis were associated with higher risk of liver-related mortality while younger age, injection drug use (IDU), problematic alcohol use and HIV/HBV co-infections were associated with a higher risk of drug-related mortality. CONCLUSIONS: DAA treatment is associated with a substantial reduction in all-cause, liver- and drug-related mortality. The association of IDU and related syndemic factors with a higher risk of drug-related mortality calls for an integrated social support, addiction, and HCV care approach among people who inject drugs. LAY SUMMARY: We assessed the effect of treatment of hepatitis C virus infection with direct-acting antiviral drugs on deaths from all causes, liver disease and drug use. We found that treatment with direct-acting antiviral drugs is associated with substantial lowering in risk of death from all causes, liver disease and drug use among people with hepatitis C virus infection.

Quantitative HPLC-MS/MS determination of Nuc, the active metabolite of remdesivir, and its pharmacokinetics in rat.

Remdesivir is a nucleotide analog prodrug that has received much attention since the outbreak of the COVID-19 pandemic in December 2019. GS-441524 (Nuc) is the active metabolite of remdesivir and plays a pivotal role in the clinical treatment of COVID-19. Here, a robust HPLC-MS/MS method was developed to determine Nuc concentrations in rat plasma samples after a one-step protein precipitation process. Chromatographic separation was accomplished on Waters XBrige C18 column (50 × 2.1 mm, 3.5 µm) under gradient elution conditions. Multiple reaction monitoring transitions in electrospray positive ion mode were m/z 292.2 → 163.2 for Nuc and 237.1 → 194.1 for the internal standard (carbamazepine). The quantitative analysis method was fully validated in line with the United States Food and Drug Administration guidelines. The linearity, accuracy and precision, matrix effect, recovery, and stability results met the requirements of the guidelines. Uncertainty of measurement and incurred sample reanalysis were analyzed to further ensure the robustness and reproducibility of the method. This optimized method was successfully applied in a rat pharmacokinetics study of remdesivir (intravenously administration, 5 mg kg-1). The method can act as a basis for further pharmacokinetic and clinical efficacy investigations in patients with COVID-19. Graphical abstract.

Loss to follow-up: A significant barrier in the treatment cascade with direct-acting therapies.

Effectiveness of direct-acting antiviral (DAA) therapies could be influenced by patient characteristics such as comorbid conditions, which could lead to premature treatment discontinuation and/or irregular medical follow-ups. Here, we evaluate loss to follow-up and treatment effectiveness of sofosbuvir/ledipasvir ± ribavirin (SOF/LDV ± RBV), ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (OBV/PTV/r + DSV ± RBV) for hepatitis C virus (HCV) genotype 1 (GT1) and sofosbuvir + ribavirin (SOF + RBV) for genotype 3 (GT3) in British Columbia Canada: The British Columbia Hepatitis Testers Cohort includes data on individuals tested for HCV since 1992, integrated with medical visit, hospitalization and prescription drug data. HCV-positive individuals who initiated DAA regimens, irrespective of treatment completion, for GT1 and GT3 until 31 December, 2017 were included. Factors associated with sustained virological response (SVR) and loss to follow-up were assessed by using multivariable logistic regression models. In total 4477 individuals initiated DAAs. The most common prescribed DAA was SOF/LDV ± RBV with SVR of 95%. The highest SVR of 99.5% was observed among OBV/PTV/r + DSV-treated patients. Overall, 453 (10.1%) individuals were lost to follow-up. Higher loss to follow-up was observed among GT1 patients treated with OBV (17.8%) and GT3 patients (15.7%). The loss to follow-up rate was significantly higher among individuals aged <60 years, those with a history of injection drug use (IDU), on opioid substitution therapy and with cirrhosis. Our findings indicate that loss to follow-up exceeds viral failure in HCV DAA therapy and its rate varies significantly by genotype and treatment regimen. Depending on the aetiology of lost to follow-up, personalized case management for those with medical complications and supporting services among IDU are needed to achieve the full benefits of effective treatments.

Effect of antiviral therapy on the outcomes of mechanically ventilated patients with herpes simplex virus detected in the respiratory tract: a systematic review and meta-analysis.

BACKGROUND: Herpes simplex virus (HSV) is frequently detected in the respiratory tract of mechanically ventilated patients. The aim of this study was to assess current evidence to determine whether antiviral therapy is associated with better outcomes in these patients. METHODS: MEDLINE, ISI Web of Science, Cochrane Database and ClinicalTrials.gov were searched from inception to 25 May 2020. All clinical studies investigating the effects of antiviral therapy on the outcome of mechanically ventilated ICU patients in whom HSV was detected in the respiratory tract were eligible for inclusion, regardless of study design, publication status or language. Titles and abstracts were reviewed independently by two authors. If the articles seemed eligible, full-text articles were reviewed and data extracted. We performed a random-effects meta-analysis to estimate relative risks (RRs) with corresponding 95% confidence intervals (CIs). The primary endpoint was hospital all-cause mortality. RESULTS: Nine studies were included in the meta-analysis (one randomized controlled trial, eight cohort studies). Antiviral treatment was associated with lower hospital mortality (with antiviral treatment, 40.6% (189 out of 465 patients); without, 52.7% (193 out of 366 patients); RR 0.74 [0.64, 0.85]; eight studies, low quality of evidence). Furthermore, antiviral treatment was associated with lower 30-day mortality (RR 0.75 [0.59, 0.94]; three studies, very low quality of evidence). We did not observe evidence for differences in ICU mortality (RR 0.73 [0.51, 1.05]; three studies, very low quality of evidence). CONCLUSIONS: This meta-analysis of the available data shows that antiviral therapy might result in lower hospital and 30-day all-cause mortality in mechanically ventilated ICU patients who are positive for HSV in the respiratory tract. However, this result must be interpreted with great caution due to the high risk of bias and limited number of patients. Large, well-designed randomized controlled clinical trials are urgently needed. TRIAL REGISTRATION: The study was registered in advance on International Prospective Register of Systematic Reviews (CRD42020180053) .

Congenital Cytomegalovirus-History, Current Practice, and Future Opportunities.

Cytomegalovirus (CMV) was first identified in the 1950s and noted to cause newborn disease in the 1960s. It is now known to be the most common cause of congenital infection in the world, leading to various central nervous system sequelae, the most common being hearing loss. Cytomegalovirus is a ubiquitous pathogen that affects nearly 30,000 infants annually in the United States, leading to 3,000-4,000 cases of hearing loss. Prevention through vaccination has proved unreliable, as has the use of immune globulin. Prevention through education has been shown to be the most effective method of minimizing infection. Antiviral therapy is effective at reducing the impact of infection on newborns. Continued global efforts will hopefully provide more solutions for this opportunistic infection.

Clinical outcomes after the introduction of direct antiviral agents for patients infected with genotype 1b hepatitis C virus depending on the regimens: A multicenter study in Korea.

BACKGROUND: A real-life study is essential outside clinical trials. The aim is to evaluate the clinical outcomes of direct acting agents (DAA) for patients with chronic hepatitis C (CHC) in real practice. METHODS: We analyzed 590 consecutively enrolled patients with CHC-1b who received DAAs since 2015, when DAAs were introduced in Korea. The patients were checked for resistance-associated variants (RAV) against nonstructural protein 5A inhibitors and then daclatasvir/asunaprevir or sofosbuvir based regimens were chosen. RESULTS: The frequency of patients with cirrhosis and prior hepatocellular carcinoma (HCC) was 29.2% and 4.7%, respectively. For the RAV test, 10% were positive and in 3.6% the result was "indeterminate." Overall, 518 patients were treated with a 24-week regimen of daclatasvir/asunaprevir, 72 patients (RAV positive 75%) were treated with 12 weeks regimen of ledipasvir/sofosbuvir or daclatasvir/sofosbuvir. The SVR12 was 94.0% in the daclatasvir/asunaprevir, 98.2% in the ledipasvir/sofosbuvir, and 100% in the daclatasvir/sofosbuvir group. A total of 93.3% of SVR12 in the RAV-"indeterminate" patients was not difference 95.0% in the RAV-negative patients. Up to 1 year, de novo HCC occurrence and recurrence developed in 2.6% and 17.8%, respectively. HCC was more frequent in cirrhotic patients than in noncirrhotic patients (P = 0.000). α Fetoprotein (AFP) level at the end of treatment was a predicting factor for de novo HCC. CONCLUSIONS: Optimizing the choice of DAAs according to RAV test resulted in high SVR among CHC-1b Korean patients. This real practice multicenter cohort study suggests the importance of AFP and HCC surveillance in cirrhotic patients even after successful HCV therapy.

Efficacy, Safety, and Predictors of Direct-acting antivirals in Hepatitis C Virus Patients with Heterogeneous Liver Diseases.

Safety, efficacy, and predictor factors of sustained-virological-response after 24 weeks of new direct-acting antivirals were evaluated in hepatitis C virus patients with different stages of hepatic disease. 260 patients, median age 60 years, of whom 48.1% cirrhotics, 17.7% liver transplant recipients, and 45.7% naïve were treated with Sofosbuvir+Ribavirine, Sofosbuvir+Simeprevir±Ribavirine, Sofosbuvir+Daclatasvir± Ribavirine, Sofosbuvir+Ledispavir±Ribavirine, Ombitasvir/Paritaprevir/Ritonavir+Ribavirine and Ombitasvir/Paritaprevir/Ritonavir+Dasabuvir±Ribavirine. Therapy outcomes, hematochemical parameters, viral replication, genotype, and resistance-associated-mutations were analyzed retrospectively. Sustained virological response was 90.4% in the whole population, 83.2% in cirrhotics, 85% in patients with previous virological failure, 93.6% in patients >60 years, and 95.6% in liver transplant recipients. SVR24 for each drug regimen was 75% Sofosbuvir+Ribavirine, 80.4% Sofosbuvir+Simeprevir±Ribavirine, 94.3% Sofosbuvir+Daclatasvir±Ribavirine, 98.7% Sofosbuvir+Ledispavir±Ribavirine, 100% Ombitasvir/ Paritaprevir/Ritonavir+Ribavirine and Ombitasvir/Paritaprevir/Ritonavir+Dasabuvir±Ribavirine. The highest sustained virological response rates were obtained with genotype-1b (95.9%). Twenty-five patients, mostly cirrhotics or suffering from severe liver complications, manifested relapse (84%), breakthrough (12%), or non-response (4%). Mild side effects were observed in 41.1% of patients. Model-for-End-Liver- Disease score <10 and alanine aminotransferase ≤20 U/L at week 8 of therapy proved positive predictors of sustained virological response. Direct-acting antiviral therapy is efficacious and safe even in patients with advanced liver disease and/ or previous virological failure; Model-for-End-Liver-Disease <10 and alanine aminotransferase reduction during therapy were found to be reliable predicting markers of sustained-virological-response.

Changes in practice and perception of hepatitis C and liver transplantation: Results of a national survey.

With new practice guidelines, it is important to understand how liver transplant (LT) centers have incorporated direct-acting antivirals (DAAs) into the management of hepatitis C virus-infected (HCV+) candidates and recipients. To explore how DAAs have affected LT centers' willingness to treat HCV+ candidates and recipients and to use HCV+ donors, we surveyed high volume US LT centers (11/2014-12/2015) regarding practices for HCV+ candidates, recipients, and donors, before vs after DAAs. We used the Scientific Registry of Transplant Recipients to compare centers' number of LTs, HCV+ recipients, and HCV+ donors in the years before (1/1/2012-12/31/2013) and after (1/1/2016-12/31/2017) survey administration. Of 80 centers contacted, 57 (71.3%) responded, representing 69.0% of the total volume of LTs in 2013. After DAAs, most centers increased treating candidates with low (≤15) model for end-stage liver disease (MELD) (85.2%), intermediate/high (>15) MELD (92.6%), and hepatocellular carcinoma (79.6%). There was consensus to treat low MELD candidates (90.8% "most of the time/always"), but less certainty for intermediate/high MELD candidates (48.2% "sometimes"). Universal post-LT HCV treatment increased (7.4% vs 57.4%). After DAAs, 42.6% were more willing to use HCV+ donors for HCV+ candidates, and 38.9% were willing to consider using HCV+ donors for HCV- candidates. Overall, with DAAs, centers were more willing to treat HCV+ candidates and recipients and to use HCV+ donors; recent recommendations may help to guide treatment decisions for intermediate/high MELD candidates.

New England BK consortium: Regional survey of BK screening and management protocols in comparison to published consensus guidelines.

INTRODUCTION: BK polyomavirus (BKPyV) continues to impact renal transplant recipients (RTR). The New England BK Consortium aims to jointly optimize screening and management of BKPyV. METHODS: Our first project was to survey centers' BKPyV screening protocols and compare them to consensus guidelines. RESULTS: Thirteen of 15 centers (86.7%) returned the survey. Only two center reported using monitoring parameters that were in line with consensus guidelines for BKPyV screening, while the majority of centers reported less intensive methods and shorter duration. One center reported performing renal biopsies in all patients with plasma viral loads >10 000 copies/mL, while all other centers only perform for-cause biopsies. For presumptive nephropathy, 11 centers recommend a biopsy for confirmation. For management of documented BKPyV-associated nephropathy, 12 centers propose further immunosuppression reduction. Nine centers report CNI dose reduction as their primary treatment. More than half of centers surveyed reported use of leflunomide, cidofovir or intravenous immunoglobulin. CONCLUSIONS: There was a large variance in BKPyV screening and management strategies among centers. Due to these results, all participating centers agreed to implement uniform screening and aim to optimize management protocols.

Compliance with the RSV immunoprophylaxis dosing schedule in the Polish registry for palivizumab (2008-2014).

OBJECTIVE: Background: Respiratory syncytial virus infection causes respiratory diseases in about 90% of the children under 2 years of age. Currently the only way to prevent infection is through immunoprophylaxis based on palivizumab. Aim: The aim of the study was to assess compliance with the recommended prophylaxis regimen in children qualified for the Polish National Programme for Respiratory Syncytial Virus Immunoprophylaxis over six consecutive virus seasons (2008-2014). PATIENTS AND METHODS: Material and methods: A retrospective analysis of data obtained from a multicentre, non-interventional observational study was performed. The prevention programme included 3,780 children aged 4 weeks to 2 years. The analysis included: the course of the neonatal period, clinical features at the time of inclusion in the programme, the immunisation course, and adherence to the palivizumab dosing schedule. RESULTS: Results: During the programme, the children received an average of 3.8 (range 1-5) injections. The highest mean number of injections was recorded in the 2013/14 season (4.3±1), and the lowest in the 2009/10 season (2.7±0.8). Overall, 3,084 children (81.7%) received all of the expected doses, while 2,352 (62.2%) children received injections within the appropriate interdose interval. The probability of non-compliance was higher for males. None of the other demographic, social, or clinical factors seemed to impact compliance. CONCLUSION: Conclusions: Compliance with the monthly dosing schedule of palivizumab is key to achieving the proper immunoprophylaxis efficacy. Education regarding the consequences of non-compliance with the regime and increased doctor-parent communication is recommended in future.

A different inhibitor is required for overcoming entecavir resistance: a comparison of four rescue therapies in a retrospective study.

AIMS: Little clinical data are available regarding re-establishing the effective inhibition of entecavir (ETV)-resistant mutants. In this retrospective study, we aimed to compare the efficacies of four treatment regimens as rescue therapy for those chronic hepatitis B (CHB) patients with ETV resistance. METHODS: A total of 65 patients with ETV resistance were assigned either with tenofovir disoproxil fumarate (TDF) monotherapy (n = 21), ETV (0.5 mg) plus adefovir (ADV) combination therapy (n = 19), ETV (1.0 mg) monotherapy (n = 11) or ETV (0.5 mg) plus TDF combination therapy (n = 14). The efficacy and safety of four treatment regimens were compared. RESULTS: There were no significant differences among the four study groups in baseline characteristics, including HBV DNA levels (χ2  = 0.749, P = 0.862) and hepatitis B e antigen-positivity (χ2  = 0.099, P = 0.992). The median reduction in serum HBV DNA level from baseline at week 48 was -2.37 ± 1.07 log10 IU ml-1 , -2.16 ± 0.81 log10 IU ml-1 , -1.17 ± 1.23 log10 IU ml-1 and -2.49 ± 1.10 log10 IU ml-1 , respectively (F = 4.078, P = 0.011). The TDF group and ETV (0.5 mg) + TDF group have the highest undetectable HBV DNA rate (76.19% vs. 78.57%) compared to the ETV (0.5 mg) + ADV group and the ETV (1.0 mg) group (63.16% vs. 18.18%, respectively). Two patients in the ETV (1.0 mg) group experienced virological breakthrough at week 48 and was attributed to poor drug adherence. CONCLUSIONS: TDF monotherapy appeared to deliver the highest undetectable HBV DNA rate in patients with ETV resistance, and ADV plus ETV combination therapy could be another choice for patients with financial restraint.

Cytomegalovirus infection management in solid organ transplant recipients across European centers in the time of molecular diagnostics: An ESGICH survey.

BACKGROUND: Scant information is available about how transplant centers are managing their use of quantitative molecular testing (QNAT) assays for active cytomegalovirus (CMV) infection monitoring in solid organ transplant (SOT) recipients. The current study was aimed at gathering information on current practices in the management of CMV infection across European centers in the era of molecular testing assays. METHODS: A questionnaire-based cross-sectional survey study was conducted by the European Study Group of Infections in Immunocompromised Hosts (ESGICH) of the Society of Clinical Microbiology and Infectious Diseases (ESCMID). The invitation and a weekly reminder with a personal link to an Internet service provider (https://es.surveymonkey.com/) was sent to transplant physicians, transplant infectious diseases specialists, and clinical virologists working at 340 European transplant centers. RESULTS: Of the 1181 specialists surveyed, a total of 173 responded (14.8%): 73 transplant physicians, 57 transplant infectious diseases specialists, and 43 virologists from 173 institutions located at 23 different countries. The majority of centers used QNAT assays for active CMV infection monitoring. Most centers preferred commercially available real-time polymerase chain reaction (RT-PCR) assays over laboratory-developed procedures for quantifying CMV DNA load in whole blood or plasma. Use of a wide variety of DNA extraction platforms and RT-PCR assays was reported. All programs used antiviral prophylaxis, preemptive therapy, or both, according to current guidelines. However, the centers used different criteria for starting preemptive antiviral treatment, for monitoring systemic CMV DNA load, and for requesting genotypic assays to detect emerging CMV-resistant variants. CONCLUSIONS: Significant variation in CMV infection management in SOT recipients still remains across European centers in the era of molecular testing. International multicenter studies are required to achieve commutability of CMV testing and antiviral management procedures.

The use of generics to treat chronic hepatitis C: not quite ready for the big stage.

Recently developed direct acting antivirals have been highly effective in treating patients with chronic hepatitis C infection. Due to their expense, there has been development of generic formulations of these medications in many countries. However, there has been controversy regarding the bioequivalence of generics when compared to brand name medications. Inactive ingredients, which may differ in generic medications, can alter the bioequivalence of the active ingredient as well as provoke intolerance or confusion among patients. There is also concern regarding the quality control and assessment of the manufacturing process of generics. When taken together these issues have the potential to lead to treatment failure. The use of generics to treat chronic hepatitis C will remain controversial, until these issues are adequately addressed.

[Expert recommendations: Hepatitis C and transplantation]. / Empfehlungen zur antiviralen Therapie der chronischen Hepatitis C bei Patienten auf der Warteliste und nach Transplantation.

With the approval of new direct acting antiviral agents (DAA), therapeutic options for patients with chronic hepatitis C virus (HCV) infection are now generally available before and after liver transplantation (LT). Interferon-free DAA regimens are highly effective therapies and provide a good safety profile. However, the body of clinical evidence in this patient population is limited and the best treatment strategies for patients on the waiting list with (de)compensated cirrhosis and after LT are not well defined. The following recommendations for antiviral therapy in the context of LT are based on the currently available literature and clinical experience of experts in the field, and have been discussed in an expert meeting. The aim of this article is to guide clinicians in the decision making when treating patients before and after LT with DAAs.

[Costs of a guideline-based treatment of patients with chronic hepatitis C in the era of interferon-free treatment]. / Kosten einer leitliniengerechten Versorgung von Hepatitis-C-Patienten im Zeitalter Interferon-freier Therapien.

The treatment of chronic hepatitis C has considerably changed with the introduction of recent direct acting antivirals. These antivirals have sustained virologic response (SVR) rates above 90 % as well as reduced toxicity and treatment duration. Therefore, current German guidelines recommend these interferon-free regimens as first-choice treatment. Nevertheless, recent developments were accompanied by a significant increase in treatment costs, which led to extensive discussions on reasonable pharmaceutical prices. The aim of the current study was to analyze the average treatment costs and costs per patient cured for guideline treatment recommendations. Analyses were stratified according to genotype, treatment status (naive/experienced), and presence/absence of cirrhosis. Costs were separated in (1.) basic diagnostic procedures, (2.) monitoring, and (3.) pharmaceuticals. The calculation is based on a remuneration scheme in the statutory health insurance system. In treatment-naïve non-cirrhotic patients, the average cost is 41 766 €/SVR for the treatment with SOF/LDV calculated (PTV/r/OMV+DSV: 53 129 €/SVR). In treatment-naive cirrhotic patients, costs were 60 323 €/SVR (SOF/LDV+RBV) and 80 604 €/SVR (PTV/r/OMV+DSV+RBV). Treatment-experienced genotype 1 patients had average costs of 60 366 €/SVR for SOF/LDV treatment as well as 53 134 €/SVR for PTV/r/OMV+DSV±RBV treatment (cirrhotic patients: 62 208 €/SVR for SOF/LDV+RBV; 80 824 €/SVR for PTV/r/OMV+DSV+RBV). The average treatment costs per SVR in treatment-naive genotype 1 patients are comparable to previous standard of care treatments and lower in treatment-experienced patients. In other genotypes, treatment costs and costs per cure are significantly higher compared to previous standard of care. However, long-term modelling studies show that new regimens are cost-effective.