Antiviral Therapy最新文献

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Safety, tolerability, pharmacokinetics, and pharmacodynamics of oral JNJ-64794964, a TLR-7 agonist, in healthy adults. 健康成人口服TLR-7激动剂JNJ-64794964的安全性、耐受性、药代动力学和药效学
IF 1.2 4区 医学
Antiviral Therapy Pub Date : 2021-05-01 DOI: 10.1177/13596535211056581
E. Gane, M. Pastagia, U. Schwertschlag, A. de Creus, C. Schwabe, J. Vandenbossche, L. Slaets, B. Fevery, Ilham Smyej, L. Wu, Rui Li, S. Siddiqui, A. Oey, C. Musto, P. van Remoortere
{"title":"Safety, tolerability, pharmacokinetics, and pharmacodynamics of oral JNJ-64794964, a TLR-7 agonist, in healthy adults.","authors":"E. Gane, M. Pastagia, U. Schwertschlag, A. de Creus, C. Schwabe, J. Vandenbossche, L. Slaets, B. Fevery, Ilham Smyej, L. Wu, Rui Li, S. Siddiqui, A. Oey, C. Musto, P. van Remoortere","doi":"10.1177/13596535211056581","DOIUrl":"https://doi.org/10.1177/13596535211056581","url":null,"abstract":"BACKGROUND\u0000This Phase I, two-part, first-in-human study assessed safety/tolerability and pharmacokinetics/pharmacodynamics of single-ascending doses (SAD) and multiple doses (MD) of the oral toll-like receptor-7 agonist, JNJ-64794964 (JNJ-4964) in healthy adults.\u0000\u0000\u0000METHODS\u0000In the SAD phase, participants received JNJ-4964 0.2 (N = 6), 0.6 (N = 6), 1.25 (N = 8) or 1.8 mg (N = 6) or placebo (N = 2/dose cohort) in a fasted state. Food effect was evaluated for the 1.25 mg cohort following ≥6 weeks washout. In the MD phase, participants received JNJ-4964 1.25 mg (N = 6) or placebo (N = 2) weekly (fasted) for 4 weeks. Participants were followed-up for 4 weeks.\u0000\u0000\u0000RESULTS\u0000No serious adverse events (AEs) occurred. 10/34 (SAD) and 5/8 (MD) participants reported mild-to-moderate (≤Grade 2), transient, reversible AEs possibly related to JNJ-4964. Five (SAD) participants had fever/flu-like AEs, coinciding with interferon-α serum levels ≥100 pg/mL and lymphopenia (<1 × 109/L), between 24-48 h after dosing and resolving approximately 96 h after dosing. One participant (MD) had an asymptomatic Grade 1 AE of retinal exudates (cotton wool spots) during follow-up, resolving 6 weeks after observation. JNJ-4964 exhibited dose-proportional pharmacokinetics, with rapid absorption (tmax 0.5-0.75 h) and distribution, and a long terminal half-life (150-591 h). Overall, no significant differences in JNJ-4964 pharmacokinetic parameters were observed in the fed versus fasted state. JNJ-4964 dose-dependently and transiently induced cytokines with potential anti-HBV activity, including interferon-α, IP-10, IL-1 RA, and/or MCP-1, and interferon-stimulated genes (ISG15, MX1, and OAS1) in serum.\u0000\u0000\u0000CONCLUSIONS\u0000In healthy adults, JNJ-4964 was generally well-tolerated, exhibited dose-proportional pharmacokinetics and induced cytokines/ISGs, with possible anti-HBV activity.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"26 3-5 1","pages":"58-68"},"PeriodicalIF":1.2,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42985887","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}
引用次数: 5
Real-life findings on the impact of the COVID-19 pandemic on HIV care 关于新冠肺炎大流行对艾滋病毒护理影响的现实调查结果
IF 1.2 4区 医学
Antiviral Therapy Pub Date : 2021-05-01 DOI: 10.1177/13596535211052215
A. Ciccullo, G. Baldin, A. Borghetti, S. Di Giambenedetto
{"title":"Real-life findings on the impact of the COVID-19 pandemic on HIV care","authors":"A. Ciccullo, G. Baldin, A. Borghetti, S. Di Giambenedetto","doi":"10.1177/13596535211052215","DOIUrl":"https://doi.org/10.1177/13596535211052215","url":null,"abstract":"The ongoing COVID-19 pandemic is rapidly reshaping the organization of healthcare systems worldwide, prompting the creation of COVID-19–dedicated wards and services at the expense of pre-existing structures. European countries are now facing the “second wave” of the COVID-19 epidemic, with increasing numbers of cases and deaths; hence, people with chronic conditions, including those living with HIV (PLWHIV), are struggling to maintain their routine disease management, resulting in missed medical visits and the risk of lower adherence to treatment. In our clinical center in Rome, Italy, we conducted a retrospective study aimed at observing how PLWHIV were followed-up during the “first wave” of the COVID-19 epidemic in the country and during the national lockdown from March 9 to May 28, 2020. We analyzed all treatment-experienced, virologically suppressed PLWHIV who had had at least one visit between March 10 and June 1, 2020, and collected viroimmunological parameters. We compared this group of PLWHIV with the patients observed over the same period in 2019. Our primary aim was to assess the rate of virological failures (VF, defined as two consecutive HIVRNA ≥ 50 copies/mL or a single HIV-RNA ≥ 1000 copies/mL). Predictors of VF were assessed using Cox regression analysis. Regarding the 2020 group, data from 341 patients were analyzed: 235 (68.9%) were males, with a median age of 54 years (Interquartile range = 46–60), a median time from HIV diagnosis of 16.1 years (IQR = 7.6–23.8), and a median time of virological suppression of 82.4 months (IQR = 31.1–142.9). With regard to antiretroviral therapy, 149 patients (43.7%) were on a 2NRTI+INI regimen, 74 (21.7%) were on 2NRTI+NNRTI, 70 (20.5%) were on a dual regimen with DTG+3 TC, 22 (6.5%) were on a regimen with 2NRTI+bPI, and 26 (7.6%) were on other regimens. Regarding the 2019 group, data from 1066 patients were available. All patients’ characteristics and differences between groups are shown in Table 1. During 184.3 Patient-Years of Follow-Up (PYFU) of the 2020 group, we observed 23 VF, a rate of 12.5 per 100 PYFU. In patients experiencing VF, we performed a genotypic test to investigate acquired mutations: among the 23 analyzed individuals, two of them, both on a 2NRTI+raltegravir (RAL) strategy, presented newly discovered mutations (one had both the 138K and the 148R mutations and the other had the 155H mutation) conferring resistance to RAL. Interestingly, patients on a dual regimen had significantly less probability of showing VF compared to patients on 3+ drug regimens: 6-month probability of remaining virologically suppressed was 98.8% vs 90.5%, respectively (log-rank p = 0.031). In the calendar period of 2019, we observed 50 VF during 675 PYFU, a rate of 7.4 per 100 PYFU. Time of virological suppression (aHR = 0.96 per month longer, 95%CI 0.95–0.98, p < 0.001) emerged as the only","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"26 1","pages":"84 - 86"},"PeriodicalIF":1.2,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44963894","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}
引用次数: 2
Low prevalence of doravirine-associated resistance mutations among polish human immunodeficiency-1 (HIV-1)-infected patients. 波兰人免疫缺陷病毒1型(HIV-1)感染患者中多拉韦林相关耐药性突变的低患病率。
IF 1.2 4区 医学
Antiviral Therapy Pub Date : 2021-05-01 DOI: 10.1177/13596535211043044
Kaja Scheibe, A. Urbańska, P. Jakubowski, M. Hlebowicz, M. Bociąga-Jasik, A. Raczyńska, A. Szymczak, B. Szetela, W. Łojewski, M. Parczewski
{"title":"Low prevalence of doravirine-associated resistance mutations among polish human immunodeficiency-1 (HIV-1)-infected patients.","authors":"Kaja Scheibe, A. Urbańska, P. Jakubowski, M. Hlebowicz, M. Bociąga-Jasik, A. Raczyńska, A. Szymczak, B. Szetela, W. Łojewski, M. Parczewski","doi":"10.1177/13596535211043044","DOIUrl":"https://doi.org/10.1177/13596535211043044","url":null,"abstract":"INTRODUCTION\u0000Doravirine (DOR) is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) that retains activity against common NNRTI resistance mutations. In this study, we aimed to investigate the prevalence of DOR resistance mutations compared with that of resistance mutations for other NNRTIs among HIV-1-infected treatment-experienced and -naïve patients from Poland.\u0000\u0000\u0000METHODS\u0000Resistance to DOR and other NNRTIs was assessed in two datasets: 1760 antiretroviral treatment-naïve HIV-1 patients and 200 treatment-experienced patients. All 1960 sequences were derived from the patients using bulk sequencing. For resistance analyses, Stanford HIV drug resistance database scores were used.\u0000\u0000\u0000RESULTS\u0000Overall, DOR resistance was present in 32 patients (1.62%), of whom 13 (0.74%) were naïve and 19 (9.50%) were treatment-experienced. The most common DOR resistance mutations observed among the naïve patients were A98G and K101E (0.2% each), and those among cART-experienced patients were L100I (2.0%), K101E, V108I, H221Y, and P225H (1.5% each). Furthermore, among the naïve patients, less common resistance to DOR (0.7%) compared with that to nevirapine (NVP) (2.1%; p = 0.0013) and rilpivirine (5.40%; p < 0.0001) was observed. For sequences obtained from treatment-experienced patients, the frequency of resistance to DOR (9.5%) was lower than that for efavirenz (25.5%; p < 0.0001) and NVP (26.0%; p < 0.0001).\u0000\u0000\u0000CONCLUSIONS\u0000The frequency of transmitted drug resistance to DOR is low, allowing for effective treatment of antiretroviral treatment-naïve patients and rapid treatment initiation. In cART-experienced patients, this agent remains an attractive NNRTI option with a higher genetic barrier to resistance.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"26 3-5 1","pages":"69-78"},"PeriodicalIF":1.2,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44437671","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}
引用次数: 3
Oseltamivir and acute hepatitis, reality association or coincidence? 奥司他韦与急性肝炎,现实关联还是巧合?
IF 1.2 4区 医学
Antiviral Therapy Pub Date : 2021-05-01 DOI: 10.1177/13596535211041494
A. Mastroianni, V. Vangeli, S. Greco, Filippo Urso, F. Greco, Luciana Chidichimo, M. Mauro
{"title":"Oseltamivir and acute hepatitis, reality association or coincidence?","authors":"A. Mastroianni, V. Vangeli, S. Greco, Filippo Urso, F. Greco, Luciana Chidichimo, M. Mauro","doi":"10.1177/13596535211041494","DOIUrl":"https://doi.org/10.1177/13596535211041494","url":null,"abstract":"Oseltamivir is an orally administered antiviral medication that selectively inhibits the influenza neuraminidase enzymes that are essential for viral replication and it is active against both influenza A and B viruses. Oseltamivir is indicated for therapy or post-exposure prevention of influenza A and B. Side effects are uncommon and include mild nausea, gastrointestinal upset, dizziness, and headache. Despite widespread use, oseltamivir has not been associated with clinically apparent liver injury; however, there is growing evidence of possible toxic liver involvement during oseltamivir therapy. To the best of our knowledge, this is the first reported case in Italy linking the development of acute hepatitis and oseltamivir therapy, in a patient suffering from influenza H1N1 infection. We also present a review of the literature on cases of oseltamivir hepatotoxicity, through the consultation of PubMed database, the bibliographical references of various articles and an extensive search using Google. In view of the analyzed results, we suggest that experts should carefully consider the need for inclusion of potential serious liver reactions be added to the oseltamivir product label.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"26 3-5 1","pages":"87-92"},"PeriodicalIF":1.2,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47129859","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}
引用次数: 1
Rilpivirine plus cobicistat-boosted darunavir as alternative to standard three-drug therapy in HIV-infected, virologically suppressed subjects: Final results of the PROBE 2 trial. 利匹韦林加钴司他体达芦那韦替代标准三药疗法治疗艾滋病毒感染、病毒抑制受试者:PROBE 2试验的最终结果。
IF 1.2 4区 医学
Antiviral Therapy Pub Date : 2021-05-01 DOI: 10.1177/13596535211042226
F. Maggiolo, N. Gianotti, L. Comí, E. di Filippo, L. Fumagalli, S. Nozza, L. Galli, D. Valenti, M. Rizzi, A. Castagna
{"title":"Rilpivirine plus cobicistat-boosted darunavir as alternative to standard three-drug therapy in HIV-infected, virologically suppressed subjects: Final results of the PROBE 2 trial.","authors":"F. Maggiolo, N. Gianotti, L. Comí, E. di Filippo, L. Fumagalli, S. Nozza, L. Galli, D. Valenti, M. Rizzi, A. Castagna","doi":"10.1177/13596535211042226","DOIUrl":"https://doi.org/10.1177/13596535211042226","url":null,"abstract":"BACKGROUND\u0000Primary analysis at 24 weeks showed that switching to rilpivirine plus darunavir/cobicistat was non-inferior to continuing a standard three-drug antiretroviral regimen in virologically suppressed people with HIV. We present efficacy and safety data from the 48-week analysis.\u0000\u0000\u0000METHODS\u0000PROBE 2 is a randomized, open-label trial. Adults who were on a three-drug therapy and had had <50 HIV-1 RNA copies/mL for at least 6 months were randomly assigned (1:1) to 25 mg rilpivirine plus 800/150 darunavir/cobicistat once daily (early switch group) or to continue their regimen for 24 weeks before switching (late switch group). In the 48-week analysis, the efficacy endpoint was the proportion of participants with <50 copies/mL of HIV-RNA (US Food and Drug Administration snapshot algorithm). The trial is registered with ClinicalTrials.gov, number NCT04064632.\u0000\u0000\u0000FINDINGS\u0000160 participants were recruited and randomized. At week 48, 70 (87.5%) in the early switch group and 76 (94.8%) in the late switch group maintained HIV-RNA <50 copies/mL. Virological failure (≥50 HIV-RNA copies/mL) was not seen in any patient of the early switch group and in 2 subjects in the late switch group none of which had treatment emergent resistance-associated mutation. Adverse events leading to treatment discontinuation occurred in 7 (8.7%) participants in the early switch group and in none in the late switch group.\u0000\u0000\u0000INTERPRETATION\u0000The combination of rilpivirine plus darunavir/cobicistat sustained virological suppression, was associated with a low frequency of virological failure, and had a favorable safety profile, which support its use as a nucleoside reverse transcriptase inhibitor-sparing and integrase inhibitor-sparing alternative to three-drug regimens.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"26 3-5 1","pages":"51-57"},"PeriodicalIF":1.2,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49614569","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}
引用次数: 0
Evaluation of doravirine-based regimen population target in a large Italian clinical center. 在意大利一家大型临床中心评估以多拉韦林为基础的方案人群目标。
IF 1.2 4区 医学
Antiviral Therapy Pub Date : 2021-05-01 DOI: 10.1177/13596535211056556
D. Farinacci, A. Ciccullo, F. Lombardi, D. Moschese, Anna D’Angelillo, V. Iannone, F. Lamanna, R. Passerotto, S. Giambenedetto
{"title":"Evaluation of doravirine-based regimen population target in a large Italian clinical center.","authors":"D. Farinacci, A. Ciccullo, F. Lombardi, D. Moschese, Anna D’Angelillo, V. Iannone, F. Lamanna, R. Passerotto, S. Giambenedetto","doi":"10.1177/13596535211056556","DOIUrl":"https://doi.org/10.1177/13596535211056556","url":null,"abstract":"BACKGROUND\u0000Doravirine (DOR) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) approved for HIV-1 infection treatment. Because of its genetic barrier, DOR appears to be a good alternative in switch strategies compared to other NNRTI. Our aim was to evaluate the percentage of people living with HIV (PLWHIV) followed in our center who could be eligible to a DOR-based regimen.\u0000\u0000\u0000METHODS\u0000We collected data from all treatment-experienced PLWHIV, never exposed to DOR and with a demonstrated virological suppression. We analyzed previous genotypic analyses, clinical history, and previous exposure to NNRTIs.\u0000\u0000\u0000RESULTS\u0000We analyzed data from 653 patients, whose characteristics are shown in Table 1. 59% of them presented no resistance mutation (RAM) at genotypic analysis. The most common DOR-related RAM were V106A, Y181V, and Y188L. We also analyzed RAM that can possibly interfere with combination therapy (mostly K65R and M184V). In the end, 81.8% of our patients results to be eligible for a DOR-based therapy regimen.\u0000\u0000\u0000CONCLUSIONS\u0000DOR represents a good option for switch strategies in virological suppressed PLWHIV. It seems to have a higher genetic barrier and a lower risk for resistance mutation development compared to other NNRTI. In our cohort, we found 81.8% of patients who could be eligible for a regimen containing DOR and almost 2/3 of patients who can be treated with the fixed-dose combination DOR/3TC/TDF.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"26 3-5 1","pages":"79-83"},"PeriodicalIF":1.2,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44266583","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}
引用次数: 1
An unexpected adverse effect: Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide–induced cholestasis 意想不到的不良反应:依维替韦/可比司他/恩曲他滨/替诺福韦-阿拉芬胺诱导的胆汁淤积
IF 1.2 4区 医学
Antiviral Therapy Pub Date : 2021-01-01 DOI: 10.1177/13596535211045832
A. Ugarte, Lorena de la Mora, M. Martinez-Rebollar, J. Mallolas, M. Laguno
{"title":"An unexpected adverse effect: Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide–induced cholestasis","authors":"A. Ugarte, Lorena de la Mora, M. Martinez-Rebollar, J. Mallolas, M. Laguno","doi":"10.1177/13596535211045832","DOIUrl":"https://doi.org/10.1177/13596535211045832","url":null,"abstract":"The morbidity and mortality of people living with HIV (PLWH) has decreased markedly after the introduction of highly effective antiretroviral therapy (ART). The safety profile of drugs used for HIV has improved over time, and nowadays, co-formulated combinations with excellent tolerability are available. One of the most commonly used is elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (EVG/COBI/FTC/TAF) due to its effectiveness in viral suppression and good tolerability [1-2]. PLWH are at greater risk of suffering hepatobiliary complications, not only caused by opportunistic infections or AIDS cholangiopathy related to advanced immunosuppression but also due to drug-induced hepatotoxicity, use of alcohol or other substances, coinfections with hepatitis virus or liver steatosis [3]. This article describes a case of a patient who developed a severe increase in cholestasis parameters after starting EVG/COBI/FTC/TAF regimen, probably related to integrase strand transfer inhibitor (InSTI). Liver enzyme elevation during InSTI-based therapy is an unusual finding. To our knowledge, this is the first report in the literature of EVG/COBI/FTC/TAF-associated cholestasis. The article tries to generate knowledge in order to strengthen pharmacovigilance of this adverse effect and reviews the available data on cholestasis in PLWH.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"26 1","pages":"9 - 12"},"PeriodicalIF":1.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45733981","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}
引用次数: 2
Pharmacokinetics, safety and tolerability of single- and multiple-ascending doses of JNJ-64530440, a novel hepatitis B virus capsid assembly modulator, in healthy volunteers 新型乙型肝炎病毒衣壳组装调节剂JNJ-64530440单次和多次递增剂量在健康志愿者中的药代动力学、安全性和耐受性
IF 1.2 4区 医学
Antiviral Therapy Pub Date : 2021-01-01 DOI: 10.1177/13596535211044331
T. Kakuda, J. Yogaratnam, C. Westland, E. Gane, C. Schwabe, Jennifer Vuong, Megha Patel, J. Snoeys, W. Talloen, O. Lenz, J. Fry, S. Chanda, P. van Remoortere
{"title":"Pharmacokinetics, safety and tolerability of single- and multiple-ascending doses of JNJ-64530440, a novel hepatitis B virus capsid assembly modulator, in healthy volunteers","authors":"T. Kakuda, J. Yogaratnam, C. Westland, E. Gane, C. Schwabe, Jennifer Vuong, Megha Patel, J. Snoeys, W. Talloen, O. Lenz, J. Fry, S. Chanda, P. van Remoortere","doi":"10.1177/13596535211044331","DOIUrl":"https://doi.org/10.1177/13596535211044331","url":null,"abstract":"Background Pharmacokinetics and safety of JNJ-64530440, a hepatitis B virus capsid assembly modulator producing normal empty capsids (CAM-N), in healthy volunteers were evaluated. Methods This Phase I study (NCT03439488) was a double-blind, randomised, placebo-controlled study. Adults (n = 10/cohort, five Asian/five non-Asian), randomised 4:1, received single-ascending doses of oral JNJ-64530440 (first- and second-generation formulations) or placebo under fasted (50, 150, 300 and 900 mg) or fed (300, 750, 1,000, 2000 and 4000 mg) conditions. Multiple-ascending doses of 750 or 2000 mg once daily and 750 mg twice daily JNJ-64530440 (second-generation formulation) for 7 days were evaluated. Pharmacokinetic parameters were estimated from plasma concentrations. Safety was assessed throughout. Results Less than dose-proportional increases in maximum plasma concentrations (Cmax) and area under the plasma concentration–time curves (AUCs) were observed across the doses. Mean plasma half-lives ranged from 9.3 to 14.5 h. Cmax and AUC were ∼two fold higher under fed versus fasting conditions and slightly higher in Asians versus Caucasians. JNJ-64530440 doses ≥750 mg achieved plasma levels higher than protein-binding adjusted concentrations demonstrating in vitro antiviral activity. No serious adverse events (AEs), treatment discontinuations or dose-limiting toxicities were seen. AE frequency/severity did not increase with dose. Conclusions Single (up to 4000 mg) and multiple doses (up to 2000 mg for 7 days) of JNJ-64530440 were well tolerated in healthy volunteers. Multiple doses ≥750 mg/day achieved plasma concentrations expected to have antiviral activity that may lower hepatitis B surface antigen. No clinically relevant differences in tolerability or pharmacokinetic parameters were seen between Asians versus Caucasians.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"26 1","pages":"13 - 24"},"PeriodicalIF":1.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45694862","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}
引用次数: 0
Comparative outcomes of lopinavir/ritonavir and hydroxychloroquine for the treatment of COVID-19 with mild-to-moderate severity: A retrospective observational study 洛匹那韦/利托那韦与羟氯喹治疗轻至中度COVID-19的疗效比较:一项回顾性观察研究
IF 1.2 4区 医学
Antiviral Therapy Pub Date : 2021-01-01 DOI: 10.1177/13596535211039394
Jeong Eun Lee, S. Lee, J. Heo, D. Kim, M. Park, Hyunjin Son, Dongkeun Kim, K. Kim, Shinwon Lee, S. H. Lee
{"title":"Comparative outcomes of lopinavir/ritonavir and hydroxychloroquine for the treatment of COVID-19 with mild-to-moderate severity: A retrospective observational study","authors":"Jeong Eun Lee, S. Lee, J. Heo, D. Kim, M. Park, Hyunjin Son, Dongkeun Kim, K. Kim, Shinwon Lee, S. H. Lee","doi":"10.1177/13596535211039394","DOIUrl":"https://doi.org/10.1177/13596535211039394","url":null,"abstract":"Background Lopinavir/ritonavir (LPV/r) and hydroxychloroquine (HCQ) are both being used to treat coronavirus disease 2019 (COVID-19), but their relative effectiveness is unknown. The purpose of this study was to compare the clinical outcomes of patients treated for COVID-19 with LPV/r or HCQ. Methods A retrospective observational study was conducted at 2 hospitals in Busan, South Korea, where approximately 90% of COVID-19 patients were hospitalised during February/March 2020. All patients aged ≥15 years that were hospitalised with mild or moderately severe COVID-19 received LPV/r or HCQ as their initial treatment and were included in the analysis. Results Among the 72 patients with mild-to-moderate disease severity on admission, 45 received LPV/r and 27 received HCQ as their initial therapy. A higher proportion of the LPV/r group had pneumonia on admission (LPV/r, 49% vs HCQ, 15%), but there were no other significant differences in the demographic or clinical characteristics between groups. Switching therapy due to clinical failure was significantly more common in the HCQ group than in the LPV/r group (41% [11/27] and 2% [1/45], respectively, P = .001). Disease progression was also significantly more common in the HCQ group than in the LPV/r group (44% [12/27] and 18% [8/45], respectively, P = .030). Conclusion Based on our study results, HCQ shows no apparent advantage compared to LPV/r for preventing progression to severe disease in patients with COVID-19.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"26 1","pages":"34 - 42"},"PeriodicalIF":1.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44320602","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}
引用次数: 1
Antiviral effect of Artemisia aucheri aqueous extract on UL46 and US6 genes of HSV-1 黄花蒿水提物对HSV-1病毒UL46和US6基因的抗病毒作用
IF 1.2 4区 医学
Antiviral Therapy Pub Date : 2021-01-01 DOI: 10.1177/13596535211039907
M. Zamanian, Z. Sharifi, Z. Noormohammadi, T. Akbarzadeh, F. Bineshian
{"title":"Antiviral effect of Artemisia aucheri aqueous extract on UL46 and US6 genes of HSV-1","authors":"M. Zamanian, Z. Sharifi, Z. Noormohammadi, T. Akbarzadeh, F. Bineshian","doi":"10.1177/13596535211039907","DOIUrl":"https://doi.org/10.1177/13596535211039907","url":null,"abstract":"HSV-1 is associated with oral lesions. Recently, anti-herpetic activity of different plant species has been investigated. In this study, the effects of Artemisia aucheri aqueous extract on the HSV-1 virus-infected Vero cells were assessed. The highest cell viability occurred in plant aqueous extracts was with a concentration of 75 μg/mL, 1–2 h before viral infection. The IC50 of the aqueous extract of 24.7 μg/ml was calculated. Most percentage of infected cell inhibition (89.6%) was with the chloroform fraction in concentration of 75 μg/ml, and the least percentage of infected cell inhibition (21.7%) was in concentration of 12.5 μg/ml with the ethyl acetate fraction in comparison with untreated control. Moreover, Q-PCR results revealed that the expression of genes UL46 and US6 were significantly reduced in the presence of different treatments utilized in the experiment. In conclusion, the present study proposes that aqueous extracts of medicinal plant Artemisia aucheri have anti-viral property and may be considered as a remedy for HSV-1 treatment.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"26 1","pages":"43 - 48"},"PeriodicalIF":1.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48671184","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}
引用次数: 2
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