Antiviral Therapy最新文献

{"title":"Discovery and development of oseltamivir at Gilead Sciences","authors":"U. Schmitz, S. Swaminathan","doi":"10.1177/13596535211067598","DOIUrl":"https://doi.org/10.1177/13596535211067598","url":null,"abstract":"John Martin’s untimely death in March 2021 was a huge loss for us personally, Gilead Sciences, the company he built over 30 years and the scientific community concerned with antiviral therapies. We wish to honor John’s legacy by retelling the discovery and history of Tamiflu and his contributions to it. Without his vision, persistence, and keen eye for opportunities, Tamiflu would not exist and Gilead’s path would not have been the same. His strategic thinking around the first oral flu drug is still quite relevant today, when we are still in the SARS-CoV-2 pandemic. John explained it simply in an interview with the Science History Institute in May 2020: “…most of my colleagues, we travel with Tamiflu when we go internationally, because it works for treatment and prevention, and hopefully, there will be a solution like that, eventually, for the Covid virus in addition to vaccines. Most people will get a flu vaccine every year, but there is still disease, we need a pill for treatment and prevention.”","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42691471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in blood lipids in patients with chronic hepatitis B after 48 weeks of tenofovir alafenamide treatment: A prospective real-world clinical study","authors":"Yeqiong Zhang, Zhipeng Li, Q. Luo, Wenxiong Xu, Lu Wang, Shu Zhu, L. Peng, Chang Xie","doi":"10.1177/13596535221082399","DOIUrl":"https://doi.org/10.1177/13596535221082399","url":null,"abstract":"Background Tenofovir alafenamide (TAF) is a new anti-hepatitis B virus nucleotide analogue that can cause dyslipidaemia in AIDS patients, but the effect of TAF on blood lipids in patients with chronic hepatitis B (CHB) is unknown. This study aimed to evaluate the effect of TAF on blood lipid levels in patients with CHB. Methods One hundred and twenty-one CHB patients were recruited as TAF group, including 69 treatment-naïve patients and 52 patients with nucleoside/nucleotide analogue experience before TAF treatment. All patients were followed up regularly for 48 weeks. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels and the incidence of dyslipidaemia before and after TAF treatment were compared. Results After 48 weeks of TAF treatment, the levels of TC, TGs and LDL-C in TAF group were significantly higher than those in control group. In TAF group, the TC and TG levels were significantly higher than that at baseline. Baseline TC and TGs levels had a significant effect on the incidence of abnormal TC and TG levels after 48 weeks treatment. The LDL-C decreased slightly but not significantly. The proportion of patients with TC abnormalities increased from 20.7% at baseline to 26.3% at week 48, LDL-C abnormalities decreased from 50.4% to 42.5% and TG abnormalities increased from 14.2% to 22.5%. There were no significant differences compared with control group, as well as compared with baseline. Conclusions Tenofovir alafenamide treatment mainly affects the TC and TG level in patients with CHB but has little effect on LDL-C.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44319361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The curing regimens of HCV: A SWOT analysis","authors":"M. Cornberg, M. Manns","doi":"10.1177/13596535211072672","DOIUrl":"https://doi.org/10.1177/13596535211072672","url":null,"abstract":"The development of direct-acting antivirals (DAA) has revolutionized the treatment of chronic hepatitis C, enabling cure of hepatitis C virus (HCV) infection in more than 95% of cases. There are essentially no contraindications, so almost any patient can now be successfully treated. The result is the prevention or amelioration of cirrhosis, hepatocellular carcinoma (HCC), and extrahepatic manifestations. Consequently, the 2020 Nobel Prize in Medicine and Physiology was awarded for the discovery of HCV. Due to the high efficacy of therapy, even global HCV elimination is conceivable even without a vaccine. Here, we would like to venture a SWOT analysis of current HCV therapies aimed at HCV elimination.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43979178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The transformation of HIV therapy: One pill once a day","authors":"Madhuchanda Choudhary, J. Mellors","doi":"10.1177/13596535211062396","DOIUrl":"https://doi.org/10.1177/13596535211062396","url":null,"abstract":"A co-formulated, one pill once a day antiretroviral regimen (single-tablet regimen), containing efavirenz, emtricitabine, and tenofovir disoproxyl fumarate (Atripla), revolutionized the antiretroviral therapy landscape. Single-tablet regimens provide not only dosing convenience but help optimize adherence and persistence with antiretroviral therapy to achieve durably suppressed viremia with both individual and societal benefits. Given the many excellent options available now, single-tablet regimens are the preferred choice for initiating antiretroviral therapy in almost all patients with rare exceptions for drug interactions and pregnancy, and for simplification of more complex antiretroviral therapy to a single-tablet regimen. In this special commemorative article, we celebrate this astounding advancement in antiretroviral therapy, championed by John C. Martin while CEO of Gilead Sciences, and its transformative impact on HIV care nationally and globally.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44712129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tenofovir alafenamide fumarate","authors":"William A Lee, A. Cheng","doi":"10.1177/13596535211067600","DOIUrl":"https://doi.org/10.1177/13596535211067600","url":null,"abstract":"Tenofovir alafenamide fumarate is a lipophilic prodrug of tenofovir which is preferentially metabolized in lymphatic tissue resulting in high concentrations of tenofovir (TFV) and its active diphosphate metabolite inside the cells that replicate HIV. Due to its selectivity for these tissues, lower total doses of TAF can be administered relative to tenofovir disoproxil fumarate (TDF) which results in improved bone and renal biomarkers. Tenofovir alafenamide fumarate has become the “backbone” of multiple combination products for the treatment of HIV, combined with emtricitabine for PreP and as a monotherapy for the treatment or HBV.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45072979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Commentary: Development of Therapeutics for Congenital Cytomegalovirus Infection","authors":"R. Whitley","doi":"10.1177/13596535211060968","DOIUrl":"https://doi.org/10.1177/13596535211060968","url":null,"abstract":"In the mid 1980’s, I flew from Birmingham, Alabama to San Francisco, rented a car, and drove to Palo Alto so that I could meet with John Martin at Syntex. John, along with Julian Verheyden, synthesized ganciclovir, which had significant in vitro activity against cytomegalovirus (CMV) in vitro. This drug provided my colleagues and me an opportunity to evaluate it as a therapeutic agent for congenital CMV infection, knowing full well that it was mutagenic, teratogenic, and carcinogenic. John in his wisdom convinced the management of Syntex to provide ganciclovir for this disease, allowing me to study this drug in symptomatic congenitally infected children through the NIAID Collaborative Antiviral Study Group (CASG). Certainly, no other person or company would advocate for the use of such a medication in children, regardless of disease severity, because of its toxicity profile. Since these early days, ganciclovir, and subsequently its prodrug valganciclovir, have become the standard of care for the treatment of congenital cytomegalovirus infection. The following commentary defines the need and progress in the development of therapy","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44304098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preemptive acyclovir to prevent herpes simplex virus bronchopneumonitis in mechanically ventilated patients with herpes simplex virus oropharyngeal reactivation: An ancillary study of the preemptive treatment for herpesviridae trial","authors":"Antoine Troger, S. Burrel, M. Pineton de Chambrun, M. Schmidt, N. Brechot, Olivier Bomme, G. Hékimian, A. Combes, D. Boutolleau, C. Luyt","doi":"10.1177/13596535211072673","DOIUrl":"https://doi.org/10.1177/13596535211072673","url":null,"abstract":"Background To evaluate the impact of preemptive acyclovir treatment on herpes simplex virus (HSV) bronchopneumonitis in mechanically ventilated patients with HSV oropharyngeal reactivation. Methods Ancillary study of the Preemptive Treatment for Herpesviridae (PTH) clinical trial. Patients included in that trial from one centre (Pitié-Salpêtrière Hospital) and in whom at least one bronchoalveolar lavage (BAL) was performed for ventilator-associated pneumonia suspicion were included in the present study. Rate of HSV bronchopneumonitis, defined as clinical symptoms suggesting of pneumonia and presence of HSV in BAL fluid ≥105 copies of HSV/106 cells, were compared in patients who received either acyclovir or placebo. Results Eighty-three patients were included; 40 having received preemptive acyclovir and 43 having received a placebo, without differences between groups at admission or at randomization. The number of patients who developed HSV bronchopneumonitis was lower among acyclovir-treated patients than among placebo-treated patients (40% vs. 72%, respectively, p = .003). Results were similar when restricted to patients without HSV detected in the lower respiratory tract at randomization (31% vs. 61%, respectively, p = .03). Conclusions Preemptive acyclovir treatment in mechanically ventilated patients with HSV oropharyngeal reactivation reduces HSV bronchopneumonitis rate.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46182379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polaris Observatory—supporting informed decision-making at the national, regional, and global levels to eliminate viral hepatitis","authors":"H. Razavi","doi":"10.1177/13596535221083179","DOIUrl":"https://doi.org/10.1177/13596535221083179","url":null,"abstract":"Background: Tools to eliminate Hepatitis B and C have been available and in 2016, the World Health Assembly endorsed the Global Health Sector Strategy for Viral Hepatitis. However, the adoption of hepatitis elimination programs has remained slow. Research design: The Center for Disease Analysis created a universal registry, the Polaris Observatory, to support informed decision-making at the national, regional, and global level for HCV and HBV elimination. The observatory covers 110 countries for HCV and 135 countries for HBV and provides decision analytics, disease burden modeling, economic impact assessments, and training to help countries with their national hepatitis elimination programs. Results: By providing reliable and up-to-date country specific data and analyses, demonstrating the impact of decisions, and providing costing estimates of national programs, our collaborating countries are making informed decisions. Our economic impact analyses also helped countries fund their elimination programs and negotiate prices. Polaris Observatory is an example of impactful private–public partnership where funding by the John C. Martin Foundation allowed support for informed decision-making by public agencies and national governments who would not/could not support such programs on their own. Conclusions: The catalytic funding allowed the Polaris Observatory to demonstrate the utility of such a program resulting in other donors to support this work. The Polaris Observatory is now supported through a portfolio of funders while our work and outputs remain independent to continue support for viral hepatitis elimination by year 2030.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44618370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiviral prophylaxis for hepatitis B virus in COVID-19 patients treated with immunosuppressive drug therapy","authors":"A. Mastroianni, S. Greco, Luciana Chidichimo, M. Mauro, Filippo Urso, V. Vangeli","doi":"10.1177/13596535211067602","DOIUrl":"https://doi.org/10.1177/13596535211067602","url":null,"abstract":"To The Editor, We read with great interest the review on COVID-19 and hepatitis B infection by Alqahtani SA and Buti M [1] underlining the need for screening and possible prophylaxis for HBV in patients with COVID-19 receiving corticosteroids and other immunosuppressive agents.The risk of HBV reactivation in patients with HBV surface antigen (HBsAg) /HBV core antibody (HBcAb)+ is estimated to be between 1 and 10% if they are taking moderate-dose (10–20 mg prednisone or equivalent) or high dose (>20 mg prednisone daily or equivalent) of corticosteroids daily for >4 weeks [2]. Hepatitis B virus reactivation can occur in HBsAg-negative patients who have only markers of previous exposure to HBV (HBcAb-positive with or without hepatitis B surface antibody [HBsAb]) [3].To investigate retrospectively the incidence of HBV reactivation in HBsAg /HBcAb+ patients, we reviewed the medical files of 450 patients with Covid-19 admitted at “Annunziata” Hub Hospital, a tertiary care hospital in Cosenza, Italy, between 6 March 2020 and 6 July 2021. Hepatitis B virus virologic indicators were determined at baseline. A total of 60 (34 males and 26 females; median age 69 year, range: 39–87) COVID-19 patients showed evidence of resolved HBV (HBsAg-negative, HBsAb-positive, HBcAb-positive). fifty-five of them patients had at least one comorbidity (most commonly hypertension, diabetes mellitus type 2, and cardiovascular diseases). Forty of the 60 patients met the criteria for severe COVID-19. Five were treated in ICU. Out of these 60 patients, all patients were given corticosteroids, 95 patients received tocilizumab, 40 patients received baricitinib, 30 patients were given anakinra, and 16 patients were treated with canakinumab. Hepatitis B virus virologic indicators were determined at baseline. There were no deaths. They all underwent antiviral prophylaxis with tenofovir disoproxil fumarate, for an average duration of 20 days (14–46 days). They also received antiviral therapy to treat the COVID-19 (remdesivir 50 and lopinavir/ritonavir 10 patients). Ten of those 60 patients had ALTabove normal range (i.e. >45 IU/L). In 12 patients with normal values of ALT at the time of admission there was a rise of ALT above normal range during hospitalization. With recovery from COVID-19, liver function gradually returned to baseline. None of the 60 patients with resolved HBV infection developed clinical evidence of HBV reactivation during 3–6 months of follow-up. We did not observe slower SarsCov2 viral clearance in these patients, while patients with higher HBsAb titers developed higher anti-SarsCov2 antibody titers. There were no adverse events attributable to anti HBV viral prophylaxis. Hepatitis B virus reactivation in subjects undergoing immunosuppressive treatment is recognized as a serious clinical problem. Although the risk of","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46818328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adefovir for lamivudine-resistant hepatitis B","authors":"Rebecca Roediger, Elizabeth Smyth, D. Dieterich","doi":"10.1177/13596535211067605","DOIUrl":"https://doi.org/10.1177/13596535211067605","url":null,"abstract":"Adefovir, a nucleotide analog developed by John Martin, was a major breakthrough in the treatment of chronic Hepatitis B. Prior to adefovir, Hepatitis B treatment was limited to two therapeutic modalities, either interferon, which carried significant side effects and was efficacious in a minority of patients, or lamivudine which showed no durable effects with short-term use and a high rate of resistance with long-term use. Adefovir was found to be effective in suppressing viral replication and in resolving the hepatic inflammation associated with hepatitis B with only rare instances of resistance. In this article, we appreciate John Martin’s contribution to science and medicine as we review the landmark trials of adefovir that brought forth a new era of treatment of Hepatitis B.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45028259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}