Antiviral Therapy最新文献

{"title":"Outcomes of etravirine-based antiretroviral treatment in treatment-experienced children and adolescents living with HIV in Europe and Thailand.","authors":"European Pregnancy And Paediatric Infections Cohort Collaboration Eppicc, Alex Lyons, Lindsay Thompson, Elizabeth Chappell, Luminita Ene, Luisa Galli, Tessa Goetghebuer, Gonzague Jourdain, Antoni Noguera-Julian, Christian R Kahlert, Christoph Königs, Pope Kosalaraksa, Pagakrong Lumbiganon, Magdalena Marczyńska, Laura Marques, Marissa Navarro, Lars Naver, Liubov Okhonskaia, Filipa Prata, Thanyawee Puthanakit, Jose T Ramos, Anna Samarina, Claire Thorne, Evgeny Voronin, Anna Turkova, Carlo Giaquinto, Ali Judd, Intira J Collins","doi":"10.1177/13596535221092182","DOIUrl":"10.1177/13596535221092182","url":null,"abstract":"<p><strong>Background: </strong>Etravirine (ETR) is approved as a component of second or third-line antiretroviral treatment (ART) for children living with HIV. We assessed the outcomes of ETR-based ART in children in routine care in Europe and Thailand.</p><p><strong>Methods: </strong>Data on children aged <18 years at ETR start were pooled from 17 observational cohorts. Characteristics at ETR start, immunological and virological outcomes at 12 months, discontinuations, adverse events (AEs) and serious adverse events (SAEs) were described. Follow-up was censored at ETR discontinuation, death or last visit.</p><p><strong>Results: </strong>177 children ever received ETR. At ETR start, median [IQR] age was 15 [12,16] years, CD4 count 480 [287, 713] cells/mm³, 70% had exposure to ≥3 ART classes and 20% had viral load (VL) <50 copies/mL. 95% received ETR in combination with ≥1 potent drug class, mostly protease inhibitor-based regimens. Median time on ETR was 24 [7, 48] months. Amongst those on ETR at 12 months (<i>n</i>=141), 69% had VL<50 copies/mL. Median CD4 increase since ETR start (<i>n</i>=83) was 147 [16, 267] cells/mm³. Overall, 81 (46%) discontinued ETR by last follow-up. Median time to discontinuation was 23 [8, 47] months. Common reasons for discontinuation were treatment simplification (19%), treatment failure (16%) and toxicity (12%). Eight children (5%) had AEs causally associated with ETR, all dermatological/hypersensitivity reactions. Two were SAEs, both Stevens-Johnson Syndrome in children on regimens containing ETR and darunavir and were causally related to either drugs; both resolved following ART discontinuation.</p><p><strong>Conclusion: </strong>Children receiving ETR were predominantly highly treatment-experienced, over two-thirds were virally suppressed at 12 months.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"27 3","pages":"13596535221092182"},"PeriodicalIF":1.3,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7614682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9703809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"JNJ-73763989 pharmacokinetics and safety: Liver-targeted siRNAs against hepatitis B virus, in Japanese and non-Japanese healthy adults, and combined with JNJ-56136379 and a nucleos(t)ide analogue in patients with chronic hepatitis B","authors":"E. Gane, M. Yuen, T. Kakuda, Tetsuro Ogawa, Yasushi Takahashi, N. Goeyvaerts, I. Lonjon‐Domanec, Tamisha Y. Vaughan, T. Schluep, J. Hamilton, E. Njumbe Ediage, V. Hillewaert, J. Snoeys, O. Lenz, W. Talloen, M. Biermer","doi":"10.1177/13596535221093856","DOIUrl":"https://doi.org/10.1177/13596535221093856","url":null,"abstract":"Background JNJ-73763989 comprises two hepatitis B virus (HBV)-specific, liver-targeted N-galactosamine-conjugated short interfering RNA triggers, JNJ-73763976 and JNJ-73763924. JNJ-73763989 pharmacokinetics, safety and tolerability were assessed in two phase 1 studies: Japanese (NCT04002752), and non-Japanese healthy participants and chronic hepatitis B (CHB) patients also receiving the HBV capsid assembly modulator JNJ-56136379 and a nucleos(t)ide analogue (NA) (NCT03365947). Methods Healthy participant cohorts were double-blind and randomized to receive a single subcutaneous JNJ-73763989 dose (non-Japanese participants, 35, 100, 200, 300 or 400 mg; Japanese participants, 25, 100 or 200 mg) or placebo. JNJ-73763976 and JNJ-73763924 plasma concentrations were assessed over 48 h. CHB patients received JNJ-73763989 200 mg every 4 weeks plus daily oral JNJ-56136379 250 mg and NA in an open-label fashion. Safety and tolerability were assessed through Day 28 (healthy participants) or Day 112 (patients). Results Thirty non-Japanese (n = 4/dose; placebo, n = 10) and 24 Japanese healthy participants (n = 6/dose; placebo, n = 6) were randomized. JNJ-73763976 and JNJ-73763924 exposure generally increased in a dose-proportional manner. Mean plasma half-life was 4–9 h. No differences between pharmacokinetic parameters were apparent between non-Japanese and Japanese healthy participants. In the 12 CHB patients, mean JNJ-73763976, JNJ-73763924 and JNJ-56136379 plasma concentrations 2 h post-dose on Day 29 were 663, 269 and 14,718 ng/mL, respectively. In both studies, all adverse events were mild/moderate. Conclusion JNJ-73763976 and JNJ-73763924 had short plasma half-lives and exposure generally increased in a dose-proportional manner; there were no pharmacokinetic differences between Japanese and non-Japanese healthy adults. JNJ-73763989 with or without JNJ-56136379 and NA was generally safe and well tolerated.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47071541","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":"A rare complication of coronary vasospasm associated with concomitant use of ergotamine, cobicistat, and darunavir","authors":"Cheng-En Wu, Chun-Hsien Wu, S. Tsai, Wen-I Liao","doi":"10.1177/13596535211068957","DOIUrl":"https://doi.org/10.1177/13596535211068957","url":null,"abstract":"Ergotism is a rare cause of peripheral vasoconstriction with varying presentation depending on the affected vessels. Coronary vasospasm is a rare, potentially fatal manifestation of ergotism. Cytochrome P-450 isoenzyme CYP3A metabolizes ergot alkaloids and their derivatives; thus, concomitant use of ergotamine and CYP3A inhibitors significantly increases ergotism risk. The antiretroviral drug darunavir boosted with cobicistat potently inhibits CYP3A. A few deleterious interactions are described in the literature when combining ergotamine with boosted human immunodeficiency virus protease inhibitors. Herein, we describe a patient who presented to the emergency department with profound coronary vasospasm arising from ergotamine’s interaction with darunavir and cobicistat. Emergency coronary angiography revealed no critical atherosclerotic stenosis, but prolonged coronary artery spasm. After prompt cardiopulmonary resuscitation, intravenous vasodilator treatment, and 14-day extracorporeal membrane oxygenation application, the patient fully recovered and was discharged. Concomitant use of ergot alkaloids and their derivatives could be disastrous for patients treated with cobicistat-boosted darunavir.","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":"47449408","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 best backbone for HIV prevention, treatment, and elimination: Emtricitabine+tenofovir.","authors":"Raymond F Schinazi, Dharmeshkumar Patel, Maryam Ehteshami","doi":"10.1177/13596535211067599","DOIUrl":"10.1177/13596535211067599","url":null,"abstract":"<p><p>The advent of antiretroviral combination therapy has significantly impacted the HIV/AIDS epidemic. No longer a death sentence, HIV infection can be controlled and suppressed using cocktail therapies that contain two or more small molecule drugs. This review aims to highlight the discovery, development, and impact of one such molecule, namely, emtricitabine (FTC, emtriva), which is one of the most successful drugs in the fight against HIV/AIDS and has been taken by over 94% of individuals infected with HIV in the USA. We also pay tribute to Dr. John C. Martin, former CEO and Chairman of Gilead Sciences, who unexpectedly passed away in 2021. A true visionary, he was instrumental in delivering FTC, as part of combination therapy with TDF (tenofovir, viread) to the global stage. As the fight to eradicate HIV marches on, we honor Dr. Martin's legacy of collaboration, achievement, and hope.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"27 2","pages":"13596535211067599"},"PeriodicalIF":1.2,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9200445","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":"Case study of hepatitis C virus control in Egypt: impact of access program","authors":"I. Waked","doi":"10.1177/13596535211067592","DOIUrl":"https://doi.org/10.1177/13596535211067592","url":null,"abstract":"Background Although Egypt was the country with the highest prevalence of hepatitis C in the world, the availability of sofosbuvir based therapies enabled Egypt to be the first country to eliminate hepatitis C and cure more than 4 million chronically infected patients. Purpose This is a small tribute to John Martin. Methodology and conclusion Here I present a summary of the HCV problem in Egypt, and how we, through Gilead's Access program under his leadership, were able to eliminate the disease.","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":"44911207","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: John C. Martin (1951–2021)","authors":"Lillian L Lou, A. Flood, Taiyin Yang, R. Whitley","doi":"10.1177/13596535211067895","DOIUrl":"https://doi.org/10.1177/13596535211067895","url":null,"abstract":"","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":"44650912","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 making of the one pill—Developing single tablet regimens for HIV and for HCV","authors":"Taiyin Yang, R. Oliyai, K. Kent","doi":"10.1177/13596535211067606","DOIUrl":"https://doi.org/10.1177/13596535211067606","url":null,"abstract":"A concept of “all or nothing” inspired the innovation of a one-pill-once-daily HIV treatment. Atripla® was the one pill that combined efavirenz, emtricitabine, and tenofovir disoproxil fumarate to become the first daily single tablet regimen that forever simplified HIV treatment to enhance patient compliance and thus, sustained viral suppression. The making of Atripla incorporated dry granulation and bilayer compression technologies to achieve stability and bioequivalence in an optimal pill size. In 2011, there lacked a standard of care for chronic hepatitis C infections that was safe, simple, short, free of interferon and ribavirin, and with high cure rates. A fixed-dose combination of ledipasvir and sofosbuvir was developed and approved in 2014 to be the first complete daily single tablet regimen for CHC genotype 1 infection. A spray-drying process for particle morphology engineering in a polymer matrix was used for improving bioavailability.","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":"46956706","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 role of tenofovir disoproxil fumarate for preventing vertical transmission of hepatitis B","authors":"C. Pan","doi":"10.1177/13596535221076640","DOIUrl":"https://doi.org/10.1177/13596535221076640","url":null,"abstract":"Background Since immunoprophylaxis failure can occur if maternal serum hepatitis B virus (HBV) DNA levels are >200,000 IU/ml, tenofovir disoproxil fumarate (TDF) therapy has been investigated for preventing mother to child transmission (PMTCT). Methods A literature search for maternal TDF therapy for PMTCT between 1/1/2015 and 7/1/21 on PUBMED, EMBASE, Cochrane, CNKI, and Wanfang databases was performed. Data from RCTs in English or Chinese were extracted and reviewed. The outcomes of interest included the efficacy and safety of TDF versus placebo for PMTCT. Results Among 11 RCTs identified from the databases, the risk-of-bias was low. All studies demonstrated that maternal TDF therapy initiated from the second or third trimester for highly viremic chronic hepatitis B mothers is highly effective and safe in the PMTCT of HBV, except one RCT performed in Thailand which showed no therapeutic advantage on TDF treatment versus placebo for PMTCT (0% vs 3% transmission). Recent emerging data suggest that maternal TDF therapy initiated at the 2nd or early 3rd trimester in mothers with HBV DNA >200,000 IU/ml achieved viremic control before delivery. In the 4-year long follow-up study for maternal TDF therapy, there were no impacts on infants’ physical growth, psychological or mental development, and bone mineral density after fetal exposure to TDF. In the light of updated efficacy and safety data from RCTs, an algorithm was proposed. The approaches in resource-limit areas were discussed. Conclusions TDF is safe for both mothers and infants as the preferred therapy for PMTCT in highly viremic mothers. TDF should be initiated at the second or early third trimester in the combination of the appropriate infants’ immunoprophylaxis.","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":"44075374","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":"Providing access to high-quality, low-cost medicines across low and middle-income countries (LMICs), working with governments and generic manufacturers around the globe - A business case","authors":"G. Alton, Clifford Samuel, A. Reddi","doi":"10.1177/13596535211068617","DOIUrl":"https://doi.org/10.1177/13596535211068617","url":null,"abstract":"Background Gilead Sciences, under Dr. John Martin’s leadership, created its Global Access Program to deliver high-quality, affordable medicines to treat and ultimately eliminate some of the world’s most challenging-to-treat, pervasive, life-limiting diseases not as philanthropy but based on a self-sustaining business model—a highly novel concept in the pharmaceutical realm. John was determined to bring together all key stakeholders from public health officials to doctors and patients around the globe to understand barriers and opportunities in HIV, viral hepatitis, and visceral leishmaniasis (VL) and in so doing, pushed the Gilead team to devise novel strategies to address healthcare disparities in resource-challenged geographies. Purpose This case study provides an overview of the evolution and impact of the Gilead Access to Medicines Program in providing treatments for HIV in low- and lower middle-income countries.","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":"45379484","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":"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}