Antiviral Therapy最新文献

{"title":"Fanconi syndrome, diabetes insipidus, and acute kidney injury due to tenofovir disoproxil fumarate: A case report.","authors":"Nthabiseng Zilwa,&nbsp;Onalethata Mpejane,&nbsp;Golam Mehboob,&nbsp;Sajan Gill,&nbsp;Thomas Kalinoski","doi":"10.1177/13596535231186727","DOIUrl":"10.1177/13596535231186727","url":null,"abstract":"<p><strong>Background: </strong>Tenofovir disoproxil fumarate is widely used in Botswana as part of the first-line antiretroviral regimen in the 'Treat All' strategy implemented in 2016 by the Ministry of Health. Its use has been associated with several uncommon adverse renal effects, though rarely all in conjunction or without the combined use of protease inhibitors.</p><p><strong>Case presentation: </strong>A 49-year-old woman living with HIV whose viral load is suppressed on tenofovir disoproxil fumarate, lamivudine, and dolutegravir presented with 1 day of generalized weakness and myalgia causing an inability to ambulate. This was associated with nausea and vomiting and profound fatigue. She was found to have an acute kidney injury, non-anion-gap metabolic acidosis, hypernatremia, hypokalemia, and hypophosphatemia. Urinalysis revealed pyuria with white blood cell casts, glucosuria, and proteinuria. The diagnosis was made of tenofovir-induced nephrotoxicity. The tenofovir was discontinued, and the patient was initiated on intravenous fluids and electrolyte and bicarbonate supplementation with improvement in her symptoms and laboratory values.</p><p><strong>Conclusions: </strong>This report suggests the possibility of severe tenofovir-induced nephrotoxicity with combined acute kidney injury, Fanconi syndrome, and nephrogenic diabetes insipidus in the absence of other provoking factors such as use with protease inhibitors or advanced HIV disease, chronic kidney disease, and age. With its wide use in Botswana and other countries, health-care providers should have a high index of suspicion for tenofovir-induced nephrotoxicity for HIV patients on tenofovir with deranged renal function tests and electrolytes.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"28 3","pages":"13596535231186727"},"PeriodicalIF":1.2,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9695435","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":"Letter to the editor on use of antibodies from convalescent sera in the treatment of moderate and severe Covid-19 infection.","authors":"Sarah B Nahhal,&nbsp;Bassem Awada,&nbsp;Joe-David Azzo,&nbsp;Rayyan Wazzi-Mkahal,&nbsp;Souha Kanj,&nbsp;Zeina A Kanafani","doi":"10.1177/13596535231186866","DOIUrl":"10.1177/13596535231186866","url":null,"abstract":"Convalescent plasma (CP) is a form of passive immunization that is used for disease prevention by transferring specific antibodies from a recovered patient to another patient with the same infection. It has been studied in the treatment of several viral infections with major conflicting results, including the Ebola virus, SARS-CoV1, and MERS-CoV. More recently, CP usage has been studied widely in the treatment of SARS-CoV2. Similar to previous studies in different outbreaks, the results have been inconsistent. In the recovery and CONCOR-1 trials, there was no difference in mortality nor clinical status at day 28 after CP infusion. On the other hand, Joyner et al. and Libster et al. showed that early infusion of high-titer CP may help in preventing clinical deterioration in mild Covid19 infection. Early in the pandemic and due to limited available therapeutic options for Covid-19 infection in Lebanon, we elected to study the efficacy of high-titer CP in moderate Covid-19 infections. A prospective and retrospective cohort study was conducted at the American University of Beirut Medical Center (AUBMC) over 14 months. It included all patients above 18 years presenting to AUBMC for moderate to severe Covid-19 infection. We excluded pregnant women and patients with a predicted survival of less than 2 days. Patients who received CP treatment (cases) in addition to standard therapy were compared to those who received standard therapy alone. The medical records for patients in both groups were reviewed and data related to demographics, medical comorbidities, symptoms upon presentation, the severity of infection on admission, laboratory findings, and treatment received were extracted. The clinical progress and laboratory data were recorded before and after receiving CP. Data were entered into a database using SPSS 29.0 (SPSS Inc, Chicago, IL). Bivariable analysis was conducted to examine the association between demographic and clinical variables with various outcome measures. The chi-square test and the independent samples t-test were used for categorical and continuous variables, respectively. A p-value of less than .05 was considered significant. We included 23 patients who received CP as cases and 46 patients as controls. Themean age in the cases group (63.4 ± 13.1 years) was more than that in the control group (60.5 ± 15.6). 52% of each group were males and 48% were females. The two groups had no significant difference in baseline demographics and medical comorbidities. Regarding the other Covid-19-related therapeutic options, corticosteroidsweremore","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"28 3","pages":"13596535231186866"},"PeriodicalIF":1.2,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9751711","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":"Lipid and glucose abnormalities and associated factors among children living with HIV in Asia.","authors":"Tulathip Suwanlerk, Dhanushi Rupasinghe, Watsamon Jantarabenjakul, Vu T An, Jeremy L Ross, Azar Kariminia, Nguyen Van Lam, Aarti Kinikar, Pradthana Ounchanum, Thanyawee Puthanakit, Nik K Nik Yusoff, Pagakrong Lumbiganon, Kulkanya Chokephaibulkit, Do C Viet, Tavitiya Sudjaritruk, Fong S Moy, Dewi K Wati, Thahira J Mohamed, Revathy Nallusamy, Nagalingeswaran Kumarasamy, Vohith Khol, Truong H Khanh, Nia Kurniati","doi":"10.1177/13596535231170751","DOIUrl":"10.1177/13596535231170751","url":null,"abstract":"<p><strong>Background: </strong>Children living with HIV (CLHIV) on prolonged antiretroviral therapy (ART) are at risk for lipid and glucose abnormalities. Prevalence and associated factors were assessed in a multicentre, Asian longitudinal paediatric cohort.</p><p><strong>Methods: </strong>CLHIV were considered to have lipid or glucose abnormalities if they had total cholesterol ≥200 mg/dL, high-density lipoprotein (HDL) ≤35 mg/dL, low-density lipoprotein (LDL) ≥100 mg/dL, triglycerides (TG) ≥110 mg/dL, or fasting glucose >110 mg/dL. Factors associated with lipid and glucose abnormalities were assessed by logistic regression.</p><p><strong>Results: </strong>Of 951 CLHIV, 52% were male with a median age of 8.0 (interquartile range [IQR] 5.0-12.0) years at ART start and 15.0 (IQR 12.0-18.0) years at their last clinic visit. 89% acquired HIV perinatally, and 30% had ever used protease inhibitors (PIs). Overall, 225 (24%) had hypercholesterolemia, 105 (27%) low HDL, 213 (58%) high LDL, 369 (54%) hypertriglyceridemia, and 130 (17%) hyperglycemia. Hypercholesterolemia was more likely among females (versus males, aOR 1.93, 95% CI 1.40-2.67). Current PIs use was associated with hypercholesterolemia (current use: aOR 1.54, 95% CI 1.09-2.20); low HDL (current use: aOR 3.16, 95% CI 1.94-5.15; prior use: aOR 10.55, 95% CI 2.53-43.95); hypertriglyceridemia (current use: aOR 3.90, 95% CI 2.65-5.74; prior use: aOR 2.89, 95% CI 1.31-6.39); high LDL (current use: aOR 1.74, 95% CI 1.09-2.76); and hyperglycemia (prior use: aOR 2.43, 95% CI 1.42-4.18).</p><p><strong>Conclusion: </strong>More than half and one-fifth of CLHIV have dyslipidemia and hyperglycemia, respectively. Routine paediatric HIV care should include metabolic monitoring. The association between PIs use and dyslipidemia emphasizes the importance of rapidly transitioning to integrase inhibitor-containing regimens.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"28 2","pages":"13596535231170751"},"PeriodicalIF":1.3,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10825667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9972626","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":"Population pharmacokinetic/pharmacodynamic models of JNJ-64794964, a toll-like receptor 7 agonist, in healthy adult participants.","authors":"Liviawati S Wu, Yue Hu, Edward J Gane, Leen Slaets, An De Creus, Yanhua Ding, Junqi Niu, Christian Schwabe, Nele Goeyvaerts, Zhongnan Xu, Dandan Huo, Marianne Tuefferd, Inge Verbrugge, Pieter Van Remoortere, Ullrich Schwertschlag, Joris Vandenbossche","doi":"10.1177/13596535231151626","DOIUrl":"10.1177/13596535231151626","url":null,"abstract":"<p><strong>Background: </strong>JNJ-4964 is a TLR7 agonist, which, via a type I interferon (IFN)-dependent mechanism, may enhance host immunity suppressed by persistent exposure to hepatitis B antigens in chronic hepatitis B.</p><p><strong>Methods: </strong>PK and PD data were pooled from 2 studies involving 90 participants (<i>n</i> = 74 JNJ-4964, dose range 0.2-1.8 mg; <i>n</i> = 16 placebo) in a fasted state. Food effects on PK were studied in 24 participants (1.2 or 1.25 mg). A population PK model and PK/PD models were developed to characterize the effect of JNJ-4964 plasma levels on the time course of IFN-α, IFN-γ-inducible protein 10 (IP-10 or CXCL10), IFN-stimulated gene 15 (<i>ISG15</i>), neopterin and lymphocytes following single and weekly dosing in healthy adults. Covariate effects, circadian rhythms and negative feedback were incorporated in the models.</p><p><strong>Results: </strong>A 3-compartment linear PK model with transit absorption adequately described JNJ-4964 PK. Bioavailability was 44.2% in fed state relative to fasted conditions. Indirect response models with maximum effect (E_max) stimulation on production rate constant (k_in) described IFN-α, IP-10, <i>ISG15</i> and neopterin, while a precursor-dependent indirect response model with inhibitory effect described the transient lymphocyte reduction. E_max, EC₅₀ and γ (steepness) estimates varied according to PD markers, with EC₅₀ displaying substantial between-subject variability. Female and Asian race exhibited lower EC₅₀, suggesting higher responsiveness.</p><p><strong>Conclusions: </strong>PK/PD models well characterized the time course of immune system markers in healthy adults. Our results supported sex and race as covariates on JNJ-4964 responsiveness, as well as circadian rhythms and negative feedback as homeostatic mechanisms that are relevant in TLR7-induced type I IFN responses.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"28 1","pages":"13596535231151626"},"PeriodicalIF":1.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9149225","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":"Pharmacokinetics of zanamivir in critically ill patients undergoing continuous venovenous hemofiltration.","authors":"André Wieringa,&nbsp;Peter Gj Ter Horst,&nbsp;GertJan Hj Wagenvoort,&nbsp;Birgit Cp Koch,&nbsp;Jasper J Haringman","doi":"10.1177/13596535221150746","DOIUrl":"https://doi.org/10.1177/13596535221150746","url":null,"abstract":"<p><strong>Background: </strong>Limited data exist for dosing of zanamivir in the setting of CVVH in the intensive care unit (ICU). Our objective is to report the pharmacokinetics and sieving coefficient (S_v) of zanamivir in patients receiving continuous venovenous hemofiltration (CVVH).</p><p><strong>Methods: </strong>In this prospective observational study, patients of ≥18 years admitted to the ICU with a life-threatening Influenza A or B infection, treated with zanamivir i.v. undergoing CVVH were included. Patients received a zanamivir loading dose of 600 mg i.v., 12 h later followed by maintenance dosages two times daily according to the treating physician. Per patient, nine CFT plasma and nine ultrafiltrate samples were drawn on day 2 of treatment and analysed with a validated HPLC-MS/MS method.</p><p><strong>Results: </strong>Four patients were included in the study. The zanamivir elimination half-life was prolonged with 5.6-9.9 h, compared to patients with normal renal function. A S_v of approximately 1.0 was identified, with unrestricted transport of zanamivir to the ultrafiltrate.</p><p><strong>Conclusions: </strong>Zanamivir is well cleared by CVVH. In absence of the possibility for therapeutic drug monitoring, the ultrafiltration rate seems as a good surrogate parameter to estimate the CL_CVVH and may help guide the dosing of zanamivir.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"28 1","pages":"13596535221150746"},"PeriodicalIF":1.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10756347","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":"Efficacy, safety and tolerability of Biktarvy in HIV-1 infection: A scoping review.","authors":"Ellen Peters,&nbsp;And Collins Iwuji","doi":"10.1177/13596535231159030","DOIUrl":"https://doi.org/10.1177/13596535231159030","url":null,"abstract":"<p><p><b>Background: </b>Biktarvy is approved for use in HIV-1 infection in both treatment-naïve and treatment-experienced individuals, after a series of successful phase III trials. However, studies on real-world evidence on its efficacy, safety and tolerability are limited. <b>Purpose: </b>The study aims to collate real-world evidence on the use of Biktarvy in clinical practice to identify gaps in knowledge. <b>Research Design: </b>Scoping review was undertaken using PRISMA guidelines and a systematic search strategy. The final search strategy used was (Bictegravir* OR biktarvy) AND (efficac* OR safe* OR effect* OR tolerab* OR 'side effect*' OR 'adverse effect*'). The last search was performed on the 12th of August 2021. <b>Study Sample: </b>Studies were eligible if they reported on the efficacy, effectiveness, safety or tolerability of bictegravir-based ART. <b>Data Collection and/or Analysis: </b>Data were collected from 17 studies that met the inclusion and exclusion criteria and summarised using a narrative synthesis. <b>Results: </b>The efficacy of Biktarvy in clinical practice is comparable to phase III trials. However, adverse effects and discontinuation rates were found to be higher in real-world studies. <b>Conclusions: </b>The cohorts in the included real-world studies showed more demographic diversity when compared to the drug approval trials, further prospective studies are required on under-represented groups such as women, pregnant people, ethnic minorities and older adults.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"28 1","pages":"13596535231159030"},"PeriodicalIF":1.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10786438","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":"Treatment-related early discontinuations and adverse events among newly diagnosed people living with HIV initiating integrase inhibitors in a real-world setting.","authors":"Charlotte-Paige Rolle,&nbsp;Jamie Castano,&nbsp;Vu Nguyen,&nbsp;Kiran Patel,&nbsp;Federico Hinestrosa,&nbsp;Edwin DeJesus","doi":"10.1177/13596535231163703","DOIUrl":"https://doi.org/10.1177/13596535231163703","url":null,"abstract":"<p><strong>Background: </strong>Cohort studies suggest higher discontinuation rates with integrase strand transfer inhibitors (INSTIs) than are seen in clinical trials. We assessed discontinuations and adverse events (AEs) that were considered related to the initial INSTI in the first year following initiation among treatment-naïve people living with HIV (PLWH).</p><p><strong>Methods: </strong>Newly diagnosed PLWH initiating raltegravir, elvitegravir/cobicistat, dolutegravir or bictegravir in combination with emtricitabine/tenofovir alafenamide or emtricitabine/tenofovir disoproxil fumarate between 10/2007 and 1/2020 at the Orlando Immunology Center were included. Unadjusted incidence rates (IRs) and incidence rate ratios (IRRs) were calculated for treatment-related discontinuations and AEs associated with the initial INSTI in the first year following initiation.</p><p><strong>Results: </strong>Of 331 enrolled, 26 (8%) initiated raltegravir, 151 (46%) initiated elvitegravir/cobicistat, 74 (22%) initiated dolutegravir and 80 (24%) initiated bictegravir. Within the first year, treatment-related discontinuations occurred in 3 on elvitegravir/cobicistat (IR 0.02 per person-years (PPY)) and 5 on dolutegravir (IR 0.08 PPY); no treatment-related discontinuations occurred among those initiating raltegravir or bictegravir. Eleven treatment-related AEs occurred in 7 on raltegravir (IR 0.46 PPY), 100 treatment-related AEs occurred in 63 on elvitegravir/cobicistat (IR 0.72 PPY), 66 treatment-related AEs occurred in 37 on dolutegravir (IR 0.97 PPY) and 65 treatment-related AEs occurred in 34 on bictegravir (IR 0.88 PPY). Unadjusted IRRs did not reveal any significant difference between INSTIs in terms of early treatment-related discontinuations or AEs.</p><p><strong>Conclusions: </strong>In our cohort, treatment-related AEs occurred in 43% initiating INSTIs but were responsible for early discontinuation in only 2% with no treatment-related discontinuations observed among those initiating RAL or BIC.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"28 2","pages":"13596535231163703"},"PeriodicalIF":1.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9359798","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":"Abacavir safety and effectiveness in young infants with HIV in South African observational cohorts.","authors":"Reneé de Waal, Helena Rabie, Karl-Günter Technau, Brian Eley, Nosisa Sipambo, Mark Cotton, Andrew Boulle, Robin Wood, Frank Tanser, Geoffrey Fatti, Matthias Egger, Mary-Ann Davies","doi":"10.1177/13596535231168480","DOIUrl":"10.1177/13596535231168480","url":null,"abstract":"<p><strong>Background: </strong>WHO guidelines recommend abacavir in first-line antiretroviral treatment for children and neonates. However, there is no approved dose <3 months of age, and data in neonates are limited.</p><p><strong>Methods: </strong>We included infants who initiated ART aged <3 months, between 2006 and 2019, in nine South African cohorts. In those who received abacavir or zidovudine, we described antiretroviral discontinuation rates; and 6- and 12-month viral suppression (<400 copies/mL). We compared infants aged <28 and ≥28 days, those weighing <3 and ≥3 kg.</p><p><strong>Results: </strong>Overall 837/1643 infants (51%) received abacavir and 443 (27%) received zidovudine. Median (interquartile range, IQR) age was 52 days (23-71), CD4 percentage was 27.9 (19.2-38.0), and weight was 4.0 kg (3.0-4.7) at ART initiation. In those with ≥1 month's follow-up, 100/718 (14%) infants discontinued abacavir, at a median of 17.5 months (IQR 6.5-39.5). Abacavir discontinuations did not differ by age or weight category (<i>p</i> = 0.4 and 0.2, respectively); and were less frequent than zidovudine discontinuations (adjusted hazard ratio 0.14, 95% confidence interval 0.10-0.20). Viral suppression at 12 months occurred in 43/79 (54%) and 130/250 (52%) of those who started abacavir aged <28 and ≥28 days, respectively (<i>p</i> = 0.8); 11/19 (58%) and 31/60 (52%) in those who weighed <3 and ≥3 kg, respectively (<i>p</i> = 0.6); and 174/329 (53%) in those on abacavir versus 77/138 (56%) in those on zidovudine (adjusted odds ratio 1.8, 95% confidence interval 1.0-3.2).</p><p><strong>Conclusion: </strong>Our data suggest that abacavir may be used safely in infants <28 days old or who weigh <3 kg.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"28 2","pages":"13596535231168480"},"PeriodicalIF":1.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10961679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9360474","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":"Inhibition of chikungunya virus replication by N-ω-Chloroacetyl-L-Ornithine in C6/36, Vero cells and human fibroblast BJ.","authors":"Lucero Rojas-Luna,&nbsp;Araceli Posadas-Modragón,&nbsp;Amanda M Avila-Trejo,&nbsp;Verónica Alcántara-Farfán,&nbsp;Lorena I Rodríguez-Páez,&nbsp;José Angel Santiago-Cruz,&nbsp;Marvin O Pastor-Alonso,&nbsp;J Leopoldo Aguilar-Faisal","doi":"10.1177/13596535231155263","DOIUrl":"https://doi.org/10.1177/13596535231155263","url":null,"abstract":"<p><strong>Background: </strong>Polyamines are involved in several cellular processes and inhibiting their synthesis affects chikungunya virus (CHIKV) replication and translation, and, therefore, reduces the quantity of infectious viral particles produced. In this study, we evaluated the inhibition of CHIKV replication by N-ω-chloroacetyl-L-ornithine (NCAO), a competitive inhibitor of ornithine decarboxylase, an enzyme which is key in the biosynthesis of polyamines (PAs).</p><p><strong>Methods: </strong>The cytotoxicity of NCAO was evaluated by MTT in cell culture. The inhibitory effect of CHIKV replication by NCAO was evaluated in Vero and C6/36 cells. The intracellular polyamines were quantified by HPLC in CHIKV-infected cells. We evaluated the yield of CHIKV in titres via the addition of PAs in Vero, C6/36 cells and human fibroblast BJ treated with NCAO.</p><p><strong>Results: </strong>We found that NCAO inhibits the replication of CHIKV in Vero and C6/36 cells in a dose-dependent manner, causing a decrease in the PFU/mL of at least 4 logarithms (<i>p</i> < 0.01) in both cell lines. Viral yields were restored by the addition of exogenous polyamines, mainly putrescine. The HPLC analyses showed that NCAO decreases the content of intracellular PAs, even though it is predominantly spermidines and spermines which are present in infected cells. Inhibition of CHIKV replication was observed in human fibroblast BJ treated with 100 μM NCAO 24 h before and 48 h after the infection at a MOI 1.</p><p><strong>Conclusions: </strong>NCAO inhibits CHIKV replication by depleting the intracellular polyamines in Vero, C6/36 cells and human fibroblast BJ, suggesting that this compound is a possible antiviral agent for CHIKV.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"28 1","pages":"13596535231155263"},"PeriodicalIF":1.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10756843","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 report and literature review: A hiccup patient developed encephalitis and duodenal perforation.","authors":"Fanfeng Kong,&nbsp;Xiao Xue Zeng","doi":"10.1177/13596535231161488","DOIUrl":"https://doi.org/10.1177/13596535231161488","url":null,"abstract":"<p><p>Brainstem encephalitis is rare and this study aims to report the clinical course, imaging features, and therapeutic response of hiccup patient with gastric ulcer who developed brainstem encephalitis with Epstein-Barr virus (EBV) detected in cerebrospinal fluid and then subsequently followed by development of duodenal perforation. Data of a gastric ulcer patient who suffered from hiccups, with brainstem encephalitis detected and then subsequently suffered from duodenal perforation were collected retrospectively and analyzed. A literature search was conducted on Epstein-Barr virus associated encephalitis using keywords like \"Epstein-Barr virus encephalitis\" and \"brainstem encephalitis,\" \"hiccup.\" The etiology of EBV-related brainstem encephalitis in this case report is not clear. However, from the initial hiccup to the presentation of both brainstem encephalitis and duodenal perforation during the course of hospitalizations builds up an uncommon case.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":"28 2","pages":"13596535231161488"},"PeriodicalIF":1.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9437220","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}