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1.
J Infect Chemother ; 29(1): 67-71, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36162643

RESUMO

INTRODUCTION: BK virus associated hemorrhagic cystitis(BKV-AHC) is a serious complication observed after allogeneic stem cell transplantation and the current therapeutic options are scarce with substantial renal side effects. Although the guidelines recommend intravenous cidofovir application with caution to nephrotoxicity, there are few studies which investigated intravesical administration and reported similar therapeutic results with less renal side effects. METHODS: We administered low dose, daily and consecutive (75 mg/day, for 5 days) intravesical cidofovir to 25 patients with BKV-AHC that developed after (ASCT). RESULTS: The response rate in our cohort was 92% and relapse was not encountered in 84% of the patient population during one year of follow-up. The median BK urine viral load significantly decreased from 260,000,000 IU/mL to 53,000,000 IU/mL after a week of treatment (p = 0.0001). Rise in serum creatinine was observed in 5 patients during treatment and post-treatment nephrotoxicity was seen in only 1 patient. CONCLUSIONS: Daily low dose intravesical cidofovir might be an effective treatment option for BKV-AHC after ASCT with favorable less systemic side effects.


Assuntos
Vírus BK , Cistite , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Transplante de Células-Tronco Hematopoéticas , Organofosfonatos , Infecções por Polyomavirus , Insuficiência Renal , Infecções Tumorais por Vírus , Humanos , Cidofovir/uso terapêutico , Cidofovir/farmacologia , Infecções por Polyomavirus/tratamento farmacológico , Infecções Tumorais por Vírus/tratamento farmacológico , Organofosfonatos/efeitos adversos , Citosina/efeitos adversos , Antivirais/efeitos adversos , Cistite/tratamento farmacológico , Cistite/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Hemorragia/tratamento farmacológico , Hemorragia/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Insuficiência Renal/etiologia
2.
Genome Med ; 14(1): 124, 2022 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-36316687

RESUMO

BACKGROUND: Ganciclovir (GCV) is widely used in solid organ and haematopoietic stem cell transplant patients for prophylaxis and treatment of cytomegalovirus. It has long been considered a mutagen and carcinogen. However, the contribution of GCV to cancer incidence and other factors that influence its mutagenicity remains unknown. METHODS: This retrospective cohort study analysed genomics data for 121,771 patients who had undergone targeted sequencing compiled by the Genomics Evidence Neoplasia Information Exchange (GENIE) or Foundation Medicine (FM). A statistical approach was developed to identify patients with GCV-associated mutational signature (GCVsig) from targeted sequenced data of tumour samples. Cell line exposure models were further used to quantify mutation burden and DNA damage caused by GCV and other antiviral and immunosuppressive drugs. RESULTS: Mutational profiles from 22 of 121,771 patient samples in the GENIE and FM cohorts showed evidence of GCVsig. A diverse range of cancers was represented. All patients with detailed clinical history available had previously undergone solid organ transplantation and received GCV and mycophenolate treatment. RAS hotspot mutations associated with GCVsig were present in 9 of the 22 samples, with all samples harbouring multiple GCV-associated protein-altering mutations in cancer driver genes. In vitro testing in cell lines showed that elevated DNA damage response and GCVsig are uniquely associated with GCV but not acyclovir, a structurally similar antiviral. Combination treatment of GCV with the immunosuppressant, mycophenolate mofetil (MMF), increased the misincorporation of GCV in genomic DNA and mutations attributed to GCVsig in cell lines and organoids. CONCLUSIONS: In summary, GCV can cause a diverse range of cancers. Its mutagenicity may be potentiated by other therapies, such as mycophenolate, commonly co-prescribed with GCV for post-transplant patients. Further investigation of the optimal use of these drugs could help reduce GCV-associated mutagenesis in post-transplant patients.


Assuntos
Infecções por Citomegalovirus , Ganciclovir , Neoplasias , Humanos , Antivirais/efeitos adversos , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/prevenção & controle , Ganciclovir/efeitos adversos , Imunossupressores/efeitos adversos , Mutação , Neoplasias/induzido quimicamente , Neoplasias/genética , Estudos Retrospectivos
3.
Lancet Gastroenterol Hepatol ; 7(12): 1112-1127, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36370741

RESUMO

BACKGROUND: To achieve WHO targets for the elimination of hepatitis C virus (HCV) as a public threat, an increased uptake of HCV treatment among people who inject drugs (PWID) is urgently needed. Optimal HCV co-located treatment models for PWID have not yet been identified. We aimed to compare two patient-centred models of HCV care in PWID with active drug use. METHODS: We did a pragmatic randomised controlled trial at eight US cities in eight opioid treatment programmes and 15 community health centres. PWID actively injecting within 90 days of study entry were randomly assigned (1:1) to either patient navigation or modified directly observed therapy (mDOT) using computer-generated variable block sizes of 2-6 stratified by city, clinical settings, and cirrhosis status. The randomisation code was concealed, in a centralised REDCap database platform, from all investigators and research staff except for an authorised data manager at the data coordinating centre. All participants received a fixed-dose combination tablet (sofosbuvir 400 mg plus velpatasvir 100 mg) orally once daily for 12 weeks. The primary outcome was sustained virological response (SVR; determined by chart review between 70 days and 365 days after end of treatment and if unavailable, by study blood draws), and secondary outcomes were treatment initiation, adherence (measured by electronic blister packs), and treatment completion. Analyses were conducted within the modified intention-to-treat (mITT; all who initiated treatment), intention-to-treat (all who were randomised), and per-protocol populations. This trial is registered with ClinicalTrials.gov, NCT02824640. FINDINGS: Between Sept 15, 2016, and Aug 14, 2018, 1891 individuals were screened and 1136 were excluded (213 declined to participate and 923 did not meet the eligibility criteria). We randomly assigned 755 participants to patient navigation (n=379) or mDOT (n=376). In the mITT sample of participants who were randomised and initiated treatment (n=623), 226 (74% [95% CI 69-79]) of 306 participants in the mDOT group and 236 (76% [69-79]) of 317 in the patient navigation group had an SVR, with no significant difference between the groups (adjusted odds ratio [AOR] 0·97 [95% CI 0·66-1·42]; p=0·35). In the ITT sample (n=755), 226 (60% [95% CI 55-65]) of 376 participants in the mDOT group and 236 (62% [57-67]) of 379 in the patient navigation group had an SVR (AOR 0·92 [0·68-1·25]; p=0·61) and in the per-protocol sample (n=501), 226 (91% [87-94]) of 248 participants in the mDOT group and 235 (93% [89-96]) of 253 in the patient navigation group had an SVR (AOR 0·79 [0·41-1·55]; p=0·44). 306 (81%) of 376 participants in the mDOT group and 317 (84%) of 379 participants in the patient navigation group initiated treatment (AOR 0·86 [0·58-1·26]; p=0·44) and, among those, 251 (82%) participants in the mDOT group and 264 (83%) participants in the patient navigation group completed treatment (AOR 0·90 [0·58-1·39]; p=0·63). Mean daily adherence was higher in the mDOT group (78% [95% CI 75-81]) versus the patient navigation group (73% [70-77]), with a difference of 4·7% ([1·9-7·4]; p=0·0010). 421 serious adverse events were reported (217 in the mDOT group and 204 in the patient navigation group), with the most common being hospital admission (176 in the mDOT group vs 161 in the patient navigation group). INTERPRETATION: In this trial of active PWID, both models resulted in high SVR. Although adherence was significantly higher in the mDOT group versus the patient navigation group, there was no significant difference in SVR between the groups. Increases in adherence and treatment completion were associated with an increased likelihood of SVR. These results suggest that active PWID can reach high SVRs in diverse settings with either mDOT or patient navigation support. FUNDING: Patient-Centered Outcomes Research Institute, Gilead Sciences, Quest Diagnostics, Monogram Biosciences, and OraSure Technologies.


Assuntos
Usuários de Drogas , Hepatite C , Abuso de Substâncias por Via Intravenosa , Humanos , Abuso de Substâncias por Via Intravenosa/complicações , Abuso de Substâncias por Via Intravenosa/tratamento farmacológico , Antivirais/efeitos adversos , Sofosbuvir/uso terapêutico , Hepatite C/tratamento farmacológico , Hepatite C/complicações , Hepacivirus
4.
J Ayub Med Coll Abbottabad ; 34(3): 447-451, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36377154

RESUMO

BACKGROUND: Pakistan has the highest prevalence of Β-Thalassemia major in children and Chronic Hepatitis C (HCV) infection is a common transfusion transmitted infection. After the emergence of new generations of Antiviral drugs labelled as Direct Acting Antivirals (DAAs), substantial eradication of HCV has been reported as 90-95% with fewer side effects as compared to older regimen of Peginterferon with or without Ribavirin. The main objective of this study was to assess the Rapid virological response (RVR) at 4th week, End of treatment response (ETR) at 12th week and sustained viral response (SVR) at 24th week achieved by using direct acting antiviral and to assess their safety. Methods: Retrospective descriptive study was conducted from July 2018 to July 2020 at National Institute of Child Health. All ß-thalassemia major paediatric patients with HCV infection and age between 3-14 years were included. Demographic data, liver function test, HCV PCR, and response of antiviral therapy was recorded and analyzed. Safety was determined by adverse effects reported in records and efficacy was documented by clearance of HCV-RNA to see ETR and SVR. RESULTS: Total 21 patients were treated. Mean age was 7.67±3yr and 12 (57%) were male. Mean weight was 19.3±3.2kg. RVR and ETR was achieved in all (100%) and SVR was achieved in 20/21 (95%) patients. Headache in 2(9.5%) and generalized body ache was found in 1 (4.25%) patient. Conclusion: Combined Sofosbuvir and Daclatasvir were found to be effective and safe for treating HCV in Thalassaemia Major Children.


Assuntos
Hepatite C Crônica , Hepatite C , Talassemia beta , Humanos , Criança , Masculino , Pré-Escolar , Adolescente , Feminino , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Antivirais/efeitos adversos , Talassemia beta/tratamento farmacológico , Estudos Retrospectivos , Hepacivirus/genética , Quimioterapia Combinada , Ribavirina/uso terapêutico , Hepatite C/tratamento farmacológico , Resultado do Tratamento , Genótipo
5.
Expert Rev Anti Infect Ther ; 20(12): 1623-1641, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36317731

RESUMO

BACKGROUND: Viral pneumonia (VP) is becoming a persistent and pervasive burden of disease. Traditional Chinese medicine Injections (TCMIs) have been proved effective in the treatment of patients with VP, which are now widely used in China. The evidence of TCMIs for VP is evolving rapidly. This study aims to assess the comparative efficacy and safety of TCMIs to provide more evidence and sights for the treatment selection of VP. RESEARCH DESIGN AND METHODS: Seven databases were searched from their inception up to 16 March 2022. Only randomized controlled trials (RCTs) are included to compare the efficacy and safety of antiviral TCMIs for the treatment of viral pneumonia. Clinical efficacy and rate of adverse events were considered as primary outcomes. RESULTS: A total of 76 RCTs with eight TCMIs comprising 7925 patients were included in the NMA. According to NMA, Reduning Injection combined with conventional antiviral drugs (CAD) produced superior effects in the effective outcomes and reduced the adverse event incidence rate of VP. CONCLUSIONS: This study indicated that TCMIs combined with CAD was more effective and safer than CAD monotherapy and compared different TCMIs therapies, which provided guidance and reference for the selection of clinical treatment medication.


Assuntos
Medicina Tradicional Chinesa , Pneumonia Viral , Humanos , Medicina Tradicional Chinesa/efeitos adversos , Metanálise em Rede , Antivirais/efeitos adversos , Pneumonia Viral/tratamento farmacológico , Injeções
6.
Antivir Ther ; 27(6): 13596535221127848, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36382358

RESUMO

BACKGROUND: Chronic hepatitis B (CHB) remains a major cause of morbidity and mortality. EDP-514 is a potent core inhibitor of hepatitis B virus (HBV) that reduces viral load reduction in HBV-infected chimeric mice. This first-in-human study evaluated the safety, tolerability, and pharmacokinetics (PK) of EDP-514 in healthy subjects and antiviral activity in patients with CHB. METHODS: In Part 1, 82 subjects received placebo or EDP-514 in fed or fasted state as single ascending doses of 50-800 mg and multiple ascending doses of 200-800 mg for 14 days. In Part 2, 24 HBV DNA-suppressed, nucleos(t)ide (NUC)-treated (i.e., NUC-suppressed) CHB patients received EDP-514 200-800 mg or placebo for 28 days. RESULTS: EDP-514 was well tolerated in healthy subjects and CHB patients with most adverse events of mild intensity. In Part 1, EDP-514 exposure increased in an approximately dose proportional manner up to 600 mg after single doses and up to 400 mg after 14-day dosing. In Part 2, EDP-514 exposure increased linearly with dose on Day 1 and Day 28, with some accumulation for Day 28 and median trough concentrations (Ctrough) approximately 20-fold above the protein-adjusted 50% effective concentration (EC50) for the dose range. Mean change in HBV RNA from baseline to Day 28 was -2.03, -1.67, -1.87, and -0.58 log U/mL in the 200 mg, 400 mg, 800 mg, and placebo CHB groups, respectively. CONCLUSIONS: EDP-514 was well tolerated, had a PK profile supporting once daily dosing, and reduced HBV RNA levels in NUC-suppressed CHB patients.


Assuntos
Hepatite B Crônica , Humanos , Camundongos , Animais , Hepatite B Crônica/tratamento farmacológico , Inibidores da Transcriptase Reversa/efeitos adversos , Voluntários Saudáveis , Vírus da Hepatite B/genética , Antivirais/efeitos adversos , RNA/farmacologia , RNA/uso terapêutico , Antígenos E da Hepatite B , DNA Viral/genética
7.
N Engl J Med ; 387(21): 1957-1968, 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36346079

RESUMO

BACKGROUND: Bepirovirsen is an antisense oligonucleotide that targets all hepatitis B virus (HBV) messenger RNAs and acts to decrease levels of viral proteins. METHODS: We conducted a phase 2b, randomized, investigator-unblinded trial involving participants with chronic HBV infection who were receiving or not receiving nucleoside or nucleotide analogue (NA) therapy. Participants were randomly assigned (in a 3:3:3:1 ratio) to receive weekly subcutaneous injections of bepirovirsen at a dose of 300 mg for 24 weeks (group 1), bepirovirsen at a dose of 300 mg for 12 weeks then 150 mg for 12 weeks (group 2), bepirovirsen at a dose of 300 mg for 12 weeks then placebo for 12 weeks (group 3), or placebo for 12 weeks then bepirovirsen at a dose of 300 mg for 12 weeks (group 4). Groups 1, 2, and 3 received loading doses of bepirovirsen. The composite primary outcome was a hepatitis B surface antigen (HBsAg) level below the limit of detection and an HBV DNA level below the limit of quantification maintained for 24 weeks after the planned end of bepirovirsen treatment, without newly initiated antiviral medication. RESULTS: The intention-to-treat population comprised 457 participants (227 receiving NA therapy and 230 not receiving NA therapy). Among those receiving NA therapy, a primary-outcome event occurred in 6 participants (9%; 95% credible interval, 0 to 31) in group 1, in 6 (9%; 95% credible interval, 0 to 43) in group 2, in 2 (3%; 95% credible interval, 0 to 16) in group 3, and 0 (0%; post hoc credible interval, 0 to 8) in group 4. Among participants not receiving NA therapy, a primary-outcome event occurred in 7 participants (10%; 95% credible interval, 0 to 38), 4 (6%; 95% credible interval, 0 to 25), 1 (1%; post hoc credible interval, 0 to 6), and 0 (0%; post hoc credible interval, 0 to 8), respectively. During weeks 1 through 12, adverse events, including injection-site reactions, pyrexia, fatigue, and increased alanine aminotransferase levels, were more common with bepirovirsen (groups 1, 2, and 3) than with placebo (group 4). CONCLUSIONS: In this phase 2b trial, bepirovirsen at a dose of 300 mg per week for 24 weeks resulted in sustained HBsAg and HBV DNA loss in 9 to 10% of participants with chronic HBV infection. Larger and longer trials are required to assess the efficacy and safety of bepirovirsen. (Funded by GSK; B-Clear ClinicalTrials.gov number, NCT04449029.).


Assuntos
Hepatite B Crônica , Hepatite B , Humanos , Hepatite B Crônica/tratamento farmacológico , Antígenos de Superfície da Hepatite B/uso terapêutico , DNA Viral , Antivirais/efeitos adversos , Hepatite B/tratamento farmacológico , Antígenos E da Hepatite B , Vírus da Hepatite B/genética , Oligonucleotídeos Antissenso/efeitos adversos , Resultado do Tratamento
8.
J Prev Med Hyg ; 63(3): E420-E423, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36415300

RESUMO

Glecaprevir (GLE)/pibrentasvir (PIB) is a pangenotypic direct-acting antiviral regimen approved for treating chronic hepatitis C virus. Primary treatment and re-treatment with GLE/PIB are effective and safe for patients without decompensated liver cirrhosis and chronic hepatitis C in a real-world clinical setting. However, in the context of compensated cirrhosis and concomitant administration of inhibitors of cytochromes, a careful monitoring of liver biomarkers, as well as therapeutic drug monitoring (TDM), may be advisable during GLE/PIB therapy. The GLE / PIB combination is very effective and safe in achieving a sustained virological response, but it can be associated with the development of severe hepatic adverse events, which require virological and serum concentration monitoring of the two drugs to prevent a serious liver damage. The possible onset of hyperbilirubinemia must not necessarily lead to the suspension of therapy, because the phenomenon may be transient. We report what is likely the first known case of severe jaundice after treatment with GLE/PIB in Italy in a patient with compensated chronic hepatitis in the context of HIV disease.


Assuntos
Infecções por HIV , Hepatite C Crônica , Icterícia , Humanos , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Antivirais/efeitos adversos , Hiperbilirrubinemia/induzido quimicamente , Hiperbilirrubinemia/tratamento farmacológico , Icterícia/induzido quimicamente , Icterícia/tratamento farmacológico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico
9.
Zhonghua Yi Xue Za Zhi ; 102(40): 3192-3200, 2022 Nov 01.
Artigo em Chinês | MEDLINE | ID: mdl-36319173

RESUMO

Objective: To systematically evaluate the efficacy and safety of different doses of antiviral drugs in the treatment of herpes zoster. Methods: PubMed, EMBASE, Cochrane Library, VIP, CNKI and WanFang database up to April 9, 2022 were searched. Two reviewers selected the studies according to inclusion and exclusion criteria, and the Cochrane bias risk assessment tool was used for quality evaluation. Data were analyzed by Revman 5.4 software for meta-analysis. The qualitative data used relative risk (RR) as the effect index, and the quantitative data used mean difference (MD) as the effect index. The point estimates and 95%CI of each effect were given. Results: Fourteen randomized controlled trials with 1 831 patients were included in the study. Compared with the 200 mg acyclovir with five times a day, the 800 mg can improve the effective rate, shorten the blister stopping time (MD=-1.29, 95%CI:-1.62- -0.96, P<0.001), relieve the pain faster (MD=-2.73, 95%CI:-4.37- -1.09, P=0.001), shorten the scabbing time (MD=-2.42, 95%CI:-2.96- -1.89, P<0.001) without increasing the adverse reaction rate (RR=1.64, 95%CI:0.80-3.36, P=0.17); Compared with the 300 mg valaciclovir with twice daily, the 900-1 000 mg valaciclovir with three times a day can improve the effective rate(RR=1.17, 95%CI:1.04-1.32, P=0.007), shorten the blister stopping time (MD=-1.53, 95%CI:-2.54- -0.51, P=0.003), relieve the pain faster (MD=-1.04, 95%CI:-1.30- -0.77, P<0.001), shorten the scabbing time (MD=-1.78, 95%CI:-2.80- -0.76, P<0.001), reduce the incidence of postherpetic neuralgia(RR=0.28, 95%CI:0.15-0.52, P<0.001) without increasing the adverse reaction rate (RR=1.47, 95%CI:0.93-2.32, P=0.10); In immunocompromised patients, compared with 1 000 mg valaciclovir with three times a day, 2 000 mg cannot significantly improve the treatment efficacy. There was no significant difference among the efficacy of 250 mg, 500 mg and 750 mg famciclovir, three times a day, in the treatment of herpes zoster. Conclusion: The 800 mg acyclovir with five times a day; 900-1 000 mg valaciclovir and 250 mg famciclovir with three times a day, are better choices in the treatment of herpes zoster.


Assuntos
Antivirais , Herpes Zoster , Humanos , Aciclovir , Antivirais/efeitos adversos , Vesícula , Famciclovir , Herpes Zoster/tratamento farmacológico , Neuralgia Pós-Herpética , Ensaios Clínicos Controlados Aleatórios como Assunto , Valaciclovir
10.
Medicine (Baltimore) ; 101(42): e31183, 2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36281168

RESUMO

INTRODUCTION: The sofosbuvir-velpatasvir single-tablet regimen (Epclusa) is a newly FDA-approved inhibitor of hepatitis C virus (HCV). This meta-analysis aimed to investigate the safety and efficacy of velpatasvir-sofosbuvir in the treatment of chronic HCV infection. METHODS: A comprehensive literature search of PubMed, Cochrane CENTRAL, EMBASE and Web of Science was conducted. Data from eligible studies were pooled in a fixed-effect meta-analysis model, using Open-Meta and RevMan software's. RESULTS: Pooled data showed that velpatasvir-sofosbuvir achieved sustained virological response (SVR12) rates of 94.2% (95% CI 90.7-97.7%, P < .001) in 1277 patients. The addition of ribavirin did not significantly increase the SVR12 (RR = 1.03, 95%CI [0.95, 1.11]) in HCV genotype-1 patients and the SVR12 (RR = 1.09, 95%CI [0.86, 1.38]) in HCV genotype-2 patients. However, adding ribavirin significantly increased SVR12 (RR = 1.13, 95% CI [1.04, 1.23]) in genotype-3 patients. CONCLUSION: In conclusion, the 12-week regimen of sofosbuvir-velpatasvir was highly effective in HCV patients. Except for genotype-3, adding ribavirin was not associated with significant improvements in SVR12 rates.


Assuntos
Hepatite C , Sofosbuvir , Humanos , Antivirais/efeitos adversos , Genótipo , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Ribavirina/uso terapêutico , Sofosbuvir/efeitos adversos , Resultado do Tratamento
11.
Antimicrob Agents Chemother ; 66(11): e0095122, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36314868

RESUMO

LHF-535 is a small-molecule antiviral currently under development as a therapeutic option to treat Lassa fever and other viral hemorrhagic fevers of arenavirus origin. The human safety and pharmacokinetics of LHF-535 were evaluated in two phase 1 trials in healthy volunteers. The first study was a double-blind, single ascending dose trial that evaluated weight-based oral doses ranging from 0.3 mg/kg in the first cohort to 40 mg/kg in the last cohort. The second study was a double-blind, multiple ascending dose trial that evaluated a 14-day oral dosing regimen, with three sequential cohorts receiving fixed doses of 450, 900, or 1,125 mg per day; the third cohort (1,125 mg/day) received a higher (loading) dose of 2,250 mg for the first dose. Each cohort in both studies consisted of eight participants randomized to either placebo (n = 2) or LHF-535 (n = 6). LHF-535 was well tolerated in both studies. Treatment-emergent adverse events were more frequent in placebo recipients than in LHF-535 recipients in both studies. LHF-535 exhibited rapid absorption, a long half-life, and exposures predicted to suppress viral replication.


Assuntos
Febres Hemorrágicas Virais , Febre Lassa , Humanos , Adulto , Febre Lassa/tratamento farmacológico , Antivirais/efeitos adversos , Antivirais/farmacocinética , Método Duplo-Cego , Voluntários Saudáveis , Relação Dose-Resposta a Droga
12.
Rev Bras Enferm ; 75(6): e20210362, 2022.
Artigo em Inglês, Português | MEDLINE | ID: mdl-36197428

RESUMO

OBJECTIVES: to analyze the occurrence of respiratory complications over the first year of life in preterm infants who did not receive palivizumab monoclonal antibodies. METHODS: analytical retrospective cohort study with preterm infants born between 2012 and 2016 in Uberlândia, state of Minas Gerais, Brazil. Data collection occurred from January to November 2018, by consulting hospital and primary healthcare medical records. Data were processed with the Poisson regression model, with p<0.05. RESULTS: of a total of 5,213 preterm births, 504 (9.7%) met the inclusion criteria. The preterm infants in this subset were assisted 2,899 times in primary care, which resulted in 1,098 (37.5%) medical diagnoses, of which 803 (78.5%) involved the respiratory tract. Preterm babies fed on formula milk at hospital discharge had more diagnoses of respiratory diseases. Maternal age (p=0.039), respiratory diagnosis at hospital discharge (p=0.028), and number of sporadic appointments (p<0.001) showed a significant association with bronchiolitis; number of sporadic appointments showed a significant association with occurrence of respiratory diseases; and breastfeeding had a protective effect against the development of bronchiolitis. CONCLUSIONS: preterm infants who did not receive palivizumab showed a high percentage of respiratory diseases, and breastfeeding helped protect them against bronchiolitis. It is recommended that these preterm babies be monitored in primary health care.


Assuntos
Bronquiolite , Doenças do Prematuro , Transtornos Respiratórios , Anticorpos Monoclonais , Antivirais/efeitos adversos , Estudos de Coortes , Feminino , Hospitalização , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/epidemiologia , Doenças do Prematuro/etiologia , Palivizumab/efeitos adversos , Estudos Retrospectivos
13.
J Cancer Res Ther ; 18(5): 1352-1359, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36204883

RESUMO

Background: This study aimed to systemically explore the risk factors of secondary infection/recurrence after ablation in patients with liver cancer. Methods: Relevant literature in PubMed, EMbase, and Cochrane Library databases were searched with keywords including "liver cancer or carcinoma," "ablation," "infectious or infection or recurrence," and "risk factor or relevant factor or correlative factor or influencing factor." Meta-analyses were performed and forest plots were drawn for risk factors, including the tumor size and location, number of tumor nodules, hepatitis B virus (HBV) DNA levels, serum alpha fetal protein (AFP) levels and serum albumin levels, Child-Pugh Class, and lack of antiviral therapy. A funnel plot was drawn to assess the publication bias. Results: A total of 23 studies were included from the initial 701 potentially relevant articles. Our meta-analyses showed that a large tumor size (odds ratio [OR] = 1.58; 95% confidence interval [CI]: 1.31-1.92); proximity to the colon, large vessels, and large hepatic vein (OR = 4.10; 95% CI: 2.26-7.43); multinodular tumor (OR = 2.10; 95% CI: 1.46-3.03), the higher HBV DNA levels (OR = 1.34; 95% CI: 1.09-0.64); higher serum AFP levels (OR = 1.56; 95% CI: 1.18-2.05), lower serum albumin levels (OR = 1.67; 95% CI: 1.06-2.65); Child-Pugh Class B and Class C (OR = 1.27; 95% CI: 1.05-1.54); and lack of antiviral therapy (OR = 1.75; 95% CI: 0.93-3.28) were associated with an increased risk of post-ablation infection/recurrence in patients with liver cancers. Conclusion: Our results indicated that the tumor size and location, number of tumor nodules, HBV DNA levels, serum AFP levels and serum albumin levels, Child-Pugh Class, and lack of antiviral therapy were the risk factors for post-ablation infection/recurrence in patients with liver cancer. Here, we have provided directions for the clinical prevention of secondary infection/recurrence in patients with liver cancer who underwent ablation therapy.


Assuntos
Carcinoma Hepatocelular , Ablação por Cateter , Coinfecção , Neoplasias Hepáticas , Antivirais/efeitos adversos , Carcinoma Hepatocelular/patologia , Ablação por Cateter/métodos , Coinfecção/tratamento farmacológico , Coinfecção/etiologia , Coinfecção/cirurgia , DNA Viral , Vírus da Hepatite B , Humanos , Neoplasias Hepáticas/patologia , Fatores de Risco , Albumina Sérica , alfa-Fetoproteínas
14.
Nefrologia (Engl Ed) ; 42(3): 311-317, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36210620

RESUMO

BACKGROUND: Remdesivir is the only antiviral treatment that has been shown to be useful against SARS-CoV-2 infection. It shorts hospitalization time compared to placebo. Its effects in Kidney transplant (KT) patients are limited to some published cases. METHODS: We performed a retrospective observational study that included all KT patients admitted between August 01, 2020 and December 31, 2020 with SARS-CoV-2 pneumonia who received remdesivir. The objective of this study was to describe the experience of a cohort of KT patients treated with remdesivir. DISCUSSION: A total of 37 KT patients developed SARS-CoV-2 infection, 7 of them received treatment with remdesivir. The rest of the patients did not receive the drug due to either CKD-EPI less than 30 mL/min or they did not present clinical criteria. In addition to remdesivir, all pacients received dexamethasone and anticoagulation therapy. 4 were men, the median age was 59 (53-71) years. Median time from transplantation was 43 (16-82) months. Chest X-rays of all patients showed pulmonary infiltrates and required low oxygen flow therapy upon admission, requiring high flow nasal therapy in 3 cases. Only 2 cases presented deterioration of the graft function, not requiring hemodialysis in any case, and all recovered renal function at hospital discharge. 2 patients rise up 1.5 times the liver function test. No patient died or required admission to the critical care unit. Median days of admission was 12 (9-27) days. CONCLUSIONS: Our study suggests that the use of remdesivir could be useful in KT patients with SARS-CoV-2 pneumonia without side effects. Additional studies are necessary with a larger number of patients to improve the knowledge of this drug in SARS-CoV-2 infection.


Assuntos
COVID-19 , Transplante de Rim , Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Anticoagulantes , Antivirais/efeitos adversos , COVID-19/tratamento farmacológico , Dexametasona , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio , SARS-CoV-2
15.
Int J Mol Sci ; 23(19)2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36232631

RESUMO

There are no data comparing the efficacy and safety of prophylactic entecavir (ETV), tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) for HBV-infected cancer patients undergoing chemotherapy. This study aimed to compare the efficacy and renal safety of ETV, TDF and TAF in this setting. HBsAg-positive cancer patients treated with ETV (n = 582), TDF (n = 200) and TAF (n = 188) during chemotherapy were retrospectively enrolled. Antiviral efficacy and risk of renal events were evaluated. The rate of complete viral suppression at 1 year was 94.7%, 94.7% and 96.1% in ETV, TDF and TAF groups, respectively (p = 0.877). A significant proportion of patients developed renal dysfunction during chemotherapy. The incidences of acute kidney injury (AKI) and chronic kidney disease stage migration were comparable among the ETV, TDF and TAF groups. TAF was relatively safe in patients with predisposing factors of AKI, including hypoalbuminemia and cisplatin use. In patients who were switched from TDF to TAF during chemotherapy, the renal function remained stable and viral suppression was well maintained after switching. In conclusion, TAF had good renal safety and comparable efficacy with ETV and TDF for HBV-infected cancer patients receiving chemotherapy. Switching from TDF to TAF during chemotherapy is safe, without a loss of efficacy.


Assuntos
Injúria Renal Aguda , Neoplasias , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/prevenção & controle , Adenina/efeitos adversos , Alanina/uso terapêutico , Antivirais/efeitos adversos , Cisplatino , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B , Humanos , Rim/fisiologia , Neoplasias/induzido quimicamente , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Estudos Retrospectivos , Tenofovir/efeitos adversos , Tenofovir/análogos & derivados , Resultado do Tratamento
16.
OMICS ; 26(11): 583-585, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36269614

RESUMO

The current pandemic has markedly shifted the focus of the global research and development ecosystem toward infectious agents such as SARS-CoV-2, the causative agent for COVID-19. A case in point is the chronic liver disease associated with hepatitis B virus (HBV) infection that continues to be a leading cause of severe liver disease and death globally. The burden of HBV infection is highest in the World Health Organization designated western Pacific and Africa regions. Tenofovir disoproxil fumarate (TDF) is a nucleoside analogue used in treatment of HBV infection but carries a potential for kidney toxicity. TDF is not metabolized by the cytochrome P450 enzymes and, therefore, its clearance in the proximal tubule of the renal nephron is controlled mostly by membrane transport proteins. Clinical pharmacogenomics of TDF with a focus on drug transporters, discussed in this perspective article, offers a timely example where resource-limited countries and regions of the world with high prevalence of HBV can strengthen the collective efforts to fight both COVID-19 and liver diseases impacting public health. We argue that precision/personalized medicine is invaluable to guide this line of research inquiry. In all, our experience in Ghana tells us that it is important not to forget the burden of chronic diseases while advancing research on infectious diseases such as COVID-19. For the long game with COVID-19, we need to address the public health burden of infectious agents and chronic diseases in tandem.


Assuntos
COVID-19 , Hepatite B Crônica , Hepatite B , Humanos , Tenofovir/efeitos adversos , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Farmacogenética , Ecossistema , Antivirais/efeitos adversos , DNA Viral/uso terapêutico , SARS-CoV-2 , Hepatite B/complicações , Hepatite B/genética , Rim , Gana
17.
PLoS Med ; 19(10): e1004120, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36260627

RESUMO

BACKGROUND: Early antiviral treatment is effective for Coronavirus Disease 2019 (COVID-19) but currently available agents are expensive. Favipiravir is routinely used in many countries, but efficacy is unproven. Antiviral combinations have not been systematically studied. We aimed to evaluate the effect of favipiravir, lopinavir-ritonavir or the combination of both agents on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) viral load trajectory when administered early. METHODS AND FINDINGS: We conducted a Phase 2, proof of principle, randomised, placebo-controlled, 2 × 2 factorial, double-blind trial of ambulatory outpatients with early COVID-19 (within 7 days of symptom onset) at 2 sites in the United Kingdom. Participants were randomised using a centralised online process to receive: favipiravir (1,800 mg twice daily on Day 1 followed by 400 mg 4 times daily on Days 2 to 7) plus lopinavir-ritonavir (400 mg/100 mg twice daily on Day 1, followed by 200 mg/50 mg 4 times daily on Days 2 to 7), favipiravir plus lopinavir-ritonavir placebo, lopinavir-ritonavir plus favipiravir placebo, or both placebos. The primary outcome was SARS-CoV-2 viral load at Day 5, accounting for baseline viral load. Between 6 October 2020 and 4 November 2021, we recruited 240 participants. For the favipiravir+lopinavir-ritonavir, favipiravir+placebo, lopinavir-ritonavir+placebo, and placebo-only arms, we recruited 61, 59, 60, and 60 participants and analysed 55, 56, 55, and 58 participants, respectively, who provided viral load measures at Day 1 and Day 5. In the primary analysis, the mean viral load in the favipiravir+placebo arm had changed by -0.57 log10 (95% CI -1.21 to 0.07, p = 0.08) and in the lopinavir-ritonavir+placebo arm by -0.18 log10 (95% CI -0.82 to 0.46, p = 0.58) compared to the placebo arm at Day 5. There was no significant interaction between favipiravir and lopinavir-ritonavir (interaction coefficient term: 0.59 log10, 95% CI -0.32 to 1.50, p = 0.20). More participants had undetectable virus at Day 5 in the favipiravir+placebo arm compared to placebo only (46.3% versus 26.9%, odds ratio (OR): 2.47, 95% CI 1.08 to 5.65; p = 0.03). Adverse events were observed more frequently with lopinavir-ritonavir, mainly gastrointestinal disturbance. Favipiravir drug levels were lower in the combination arm than the favipiravir monotherapy arm, possibly due to poor absorption. The major limitation was that the study population was relatively young and healthy compared to those most affected by the COVID-19 pandemic. CONCLUSIONS: At the current doses, no treatment significantly reduced viral load in the primary analysis. Favipiravir requires further evaluation with consideration of dose escalation. Lopinavir-ritonavir administration was associated with lower plasma favipiravir concentrations. TRIAL REGISTRATION: Clinicaltrials.gov NCT04499677 EudraCT: 2020-002106-68.


Assuntos
COVID-19 , Humanos , COVID-19/tratamento farmacológico , Lopinavir/uso terapêutico , Pandemias , Ritonavir/uso terapêutico , Antivirais/efeitos adversos , SARS-CoV-2 , Resultado do Tratamento
18.
Ter Arkh ; 94(1): 83-93, 2022 Jan 15.
Artigo em Russo | MEDLINE | ID: mdl-36286922

RESUMO

AIM: To evaluate the efficacy and safety of Raphamin, containing technologically processed affinity-purified antibodies to interferon , CD4 receptor, 1 domain of the major histocompatibility complex class II and 2 microglobulin major histocompatibility complex class I in the treatment of acute respiratory viral infection (ARVI), including influenza, in adults. MATERIALS AND METHODS: 240 patients 1870 years old with ARVI were included in a phase III (20192020), randomized, double-blind, placebo-controlled trial. Pregnant women, patients with suspected bacterial infections were excluded from the study. Raphamin/placebo was prescribed for 5 days within 24 hours of the illness onset. Primary endpoint was a time to resolution of ARVI (Polymerase chain reaction PCR-confirmed). Additionally, the severity of ARVI, proportion of patients with ARVI resolution/worsening/complications, frequency of antipyretics prescription, and time to resolution of symptoms of ARVI (including PCR non confirmed) were assessed. RESULTS: The average time to resolution of ARVI (PCR-confirmed) was 4.11.9 [4.01.9] and 5.02.5 [5.02.5] days in the Raphamin/placebo groups (ITT and [PP] analysis, р=0.0155 and [р=0.0114], respectively). The duration of ARVI decreased by 0.892.23 [0.932.25] days. Superiority of Raphamin was shown during therapy period according to the ARVI resolution criterion (р=0.0014 [р=0.0005]). There were no statistically significant difference in the severity of ARVI and frequency of antipyretics prescription. The proportion of patients with worsening/complications was 0 [0]% and 2.5 [2.8]% in the Raphamin and placebo groups, respectively. Favorable safety profile of Raphamin (including the incidence and severity of adverse events) and high compliance were shown. CONCLUSION: Raphamin promotes significant decrease, practically by a day, the duration of ARVI, including influenza.


Assuntos
Antipiréticos , Influenza Humana , Infecções Respiratórias , Viroses , Adulto , Humanos , Feminino , Gravidez , Antivirais/efeitos adversos , Influenza Humana/tratamento farmacológico , Influenza Humana/epidemiologia , Antipiréticos/uso terapêutico , Antígenos CD4/uso terapêutico , Viroses/tratamento farmacológico , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/epidemiologia , Método Duplo-Cego , Anticorpos , Interferons/uso terapêutico , Resultado do Tratamento
19.
In Vivo ; 36(6): 2918-2922, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36309363

RESUMO

BACKGROUND/AIM: The aim of this study was to determine the safety and efficacy of a direct-acting antiviral treatment, ombitasvir/paritaprevir/ritonavir and dasabuvir, without ribavirin, in a real-life setting. PATIENTS AND METHODS: We performed a prospective observational study including 108 patients undergoing hemodialysis for end-stage kidney disease, referred to our clinic for antiviral therapy for chronic hepatitis C virus infection. Patients received treatment with ombitasvir/paritaprevir/ritonavir and dasabuvir, for 12 weeks. Sustained virologic response (SVR) was defined as undetectable viremia at 12 weeks after the end of therapy. For safety analysis, we monitored serum levels of hemoglobin, albumin, total bilirubin, alanine-aminotransferase and aspartate- aminotransferase at the beginning and end of therapy, as well as at SVR. Verbal Numeric Rating Scale was used to assess the presence of nausea, headaches and fatigue. RESULTS: We noted a high prevalence of diabetic and hypertensive nephropathy as the underlying cause of chronic kidney disease. Most of the patients had F2 and F3 liver fibrosis (32.40% and 34.25%, respectively). The SVR rate was 96.2% (103/107 patients). We recorded an unrelated death after the completion of antiviral therapy. We found increased levels of nausea, headaches and fatigue at the end of therapy compared to at initiation, The presence and degree of symptoms did not correlate with the underlying cause of renal disease (p=0.72) nor with the degree of fibrosis (p=0.08). Minimal increases in transaminases and bilirubin were recorded at the end of treatment, with no statistical significance. CONCLUSION: Oral antiviral therapy with ombitasvir/paritaprevir/ritonavir and dasabuvir can be safely used in hemodialysis patients, with similar response rates compared to the general population.


Assuntos
Hepatite C Crônica , Hepatite C , Compostos Macrocíclicos , Humanos , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Antivirais/efeitos adversos , Ritonavir/efeitos adversos , Hepacivirus/genética , Compostos Macrocíclicos/efeitos adversos , Quimioterapia Combinada , Valina/uso terapêutico , Genótipo , Carbamatos/efeitos adversos , Anilidas/efeitos adversos , Diálise Renal/efeitos adversos , Bilirrubina/uso terapêutico , Transaminases/uso terapêutico , Fadiga , Cefaleia/induzido quimicamente , Cefaleia/tratamento farmacológico , Náusea/induzido quimicamente , Prolina/uso terapêutico , Resultado do Tratamento
20.
Eur J Clin Pharmacol ; 78(11): 1813-1821, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36066651

RESUMO

PURPOSE: Nitazoxanide is a broad-spectrum antiparasitic that has been tested for COVID-19 due to its anti-inflammatory effects and in vitro antiviral activity. This study synthesized the best evidence on the efficacy and safety of nitazoxanide in COVID-19. METHODS: Searches for studies were performed in peer-reviewed and grey-literature from January 1, 2020 to May 23, 2022. The following elements were used to define eligibility criteria: (1) Population: individuals with COVID-19; (2) Intervention: nitazoxanide; (3) Comparison: placebo; (4) Outcomes: primary outcome was death, and secondary outcomes were viral load, positive RT-PCR status, serum biomarkers of inflammation, composite measure of disease progression (ICU admission or invasive mechanical ventilation), and any adverse events; (5) Study type: blinded, placebo-controlled, randomized clinical trials (RCTs). Treatment effects were reported as relative risk (RR) for dichotomous variables and standardized mean difference (SMD) for continuous variables with 95% confidence intervals (CI). RESULTS: Five blinded, placebo-controlled RCTs were included and enrolled individuals with mild or moderate SARS-CoV-2 infection. We found no difference between nitazoxanide and placebo in reducing viral load (SMD = - 0.16; 95% CI - 0.38 to 0.05) and the frequency of positive RTP-PCR results (RR = 0.92; 95% CI 0.81 to 1.06). In addition, there was no decreased risk for disease progression (RR = 0.63; 95% CI 0.38 to 1.04) and death (RR = 0.81; 95% CI 0.36 to 1.78) among patients receiving nitazoxanide. Patients with COVID-19 treated with nitazoxanide had decreased levels of white blood cells (SMD = - 0.15; 95% - 0.29 to - 0.02), lactate dehydrogenase (LDH) (SMD - 0.32; 95% - 0.52 to - 0.13), and D-dimer (SMD - 0.49; 95% CI - 0.68 to - 0.31) compared to placebo, but the magnitude of effect was considered small to moderate. CONCLUSION: This systematic review showed no evidence of clinical benefits of the use of nitazoxanide to treat patients with mild or moderate COVID-19. In addition, we found a reduction in WBC, LDH, and D-dimer levels among nitazoxanide-treated patients, but the effect size was considered small to moderate.


Assuntos
COVID-19 , Anti-Inflamatórios , Antiparasitários , Antivirais/efeitos adversos , COVID-19/tratamento farmacológico , Progressão da Doença , Humanos , Lactato Desidrogenases , Nitrocompostos , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2 , Tiazóis
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