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Journal of Microbiology, Immunology,... Oct 2021Despite aggressive efforts on containment measures for the coronavirus disease 2019 (COVID-19) pandemic around the world, severe acute respiratory syndrome coronavirus 2... (Review)
Review
Despite aggressive efforts on containment measures for the coronavirus disease 2019 (COVID-19) pandemic around the world, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously spreading. Therefore, there is an urgent need for an effective antiviral agent. To date, considerable research has been conducted to develop different approaches to COVID-19 therapy. In addition to early observational studies, which could be limited by study design, small sample size, non-randomized design, or different timings of treatment, an increasing number of randomized controlled trials (RCTs) investigating the clinical efficacy and safety of antiviral agents are being carried out. This study reviews the updated findings of RCTs regarding the clinical efficacy of eight antiviral agents against COVID-19, including remdesivir, lopinavir/ritonavir, favipiravir, sofosbuvir/daclatasvir, sofosbuvir/ledipasvir, baloxavir, umifenovir, darunavir/cobicistat, and their combinations. Treatment with remdesivir could accelerate clinical improvement; however, it lacked additional survival benefits. Moreover, 5-day regimen of remdesivir might show adequate effectiveness in patients with mild to moderate COVID-19. Favipiravir was only marginally effective regarding clinical improvement and virological assessment based on the results of small RCTs. The present evidence suggests that sofosbuvir/daclatasvir may improve survival and clinical outcomes in patients with COVID-19. However, the sample sizes for analysis were relatively small, and all studies were exclusively conducted in Iran. Further larger RCTs in other countries are warranted to support these findings. In contrast, the present findings of limited RCTs did not indicate the use of lopinavir/ritonavir, sofosbuvir/ledipasvir, baloxavir, umifenovir, and darunavir/cobicistat in the treatment of patients hospitalized for COVID-19.
Topics: Adenosine Monophosphate; Alanine; Amides; Antiviral Agents; Carbamates; Cobicistat; Darunavir; Dibenzothiepins; Drug Combinations; Drug Therapy, Combination; Humans; Imidazoles; Indoles; Iran; Lopinavir; Morpholines; Pyrazines; Pyridones; Pyrrolidines; Randomized Controlled Trials as Topic; Ritonavir; SARS-CoV-2; Sofosbuvir; Treatment Outcome; Triazines; Valine; COVID-19 Drug Treatment
PubMed: 34253490
DOI: 10.1016/j.jmii.2021.05.011 -
PloS One 2021Sofosbuvir seems to be a revolutionary treatment for Hepatitis C-infected patients with advanced chronic kidney disease (CKD) but existing evidence is not quite... (Meta-Analysis)
Meta-Analysis
Sofosbuvir seems to be a revolutionary treatment for Hepatitis C-infected patients with advanced chronic kidney disease (CKD) but existing evidence is not quite adequate. The aim of this study was to evaluate the efficacy and safety of Sofosbuvir-based therapy without Ribavirin for all hepatitis C virus genotypes among patients with advanced CKD. We conducted an updated systematic literature search from the beginning of 2013 up to June 2020. Sustained virologic response (SVR) rate at 12 and/or 24 weeks after the end of treatment, and adverse events in HCV-infected patients with advanced CKD were pooled using random effects models. We included 27 published articles in our meta-analyses, totaling 1,464 HCV-infected patients with advanced CKD. We found a substantial heterogeneity based on the I2 index (P = 0.00, I2 = 56.1%). The pooled SVR rates at 12 and 24 weeks after the end of Sofosbuvir-based treatment were 97% (95% Confidence Interval: 95-99) and 95% (89-99) respectively. The pooled SVR12 rates were 98% (96-100) and 94% (90-97) in patients under 60 and over 60 years old respectively. The pooled incidence of severe adverse events was 0.11 (0.04-0.19). The pooled SVR12 rate after completion of the half dose regimen was as high as the full dose treatment but it was associated with less adverse events (0.06 versus 0.14). The pooled SVR12 rate was 98% (91-100) in cirrhotic patients and 100% (98-100) in non-cirrhotic patients. The endorsement of Sofosbuvir-based regimen can improve the treatment of hepatitis C virus infection in patients with advanced CKD.
Topics: Antiviral Agents; Hepatitis C; Hepatitis C, Chronic; Humans; Renal Insufficiency, Chronic; Sofosbuvir; Treatment Outcome
PubMed: 33566846
DOI: 10.1371/journal.pone.0246594 -
Nefrologia 2021Hepatitis C is an important agent of liver damage in patients with chronic kidney disease and the advent of DAAs has dramatically changed the management of HCV positive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hepatitis C is an important agent of liver damage in patients with chronic kidney disease and the advent of DAAs has dramatically changed the management of HCV positive patients, including those with advanced CKD. Sofosbuvir is the backbone of many anti-HCV regimens based on DAAs but it remains unclear whether it is appropriate for HCV-infected patients with stage 4-5 CKD.
STUDY AIMS AND DESIGN
We performed a systematic review of the literature with a meta-analysis of clinical studies in order to evaluate the efficacy and safety of SOF-based DAA regimens in patients with stage 4-5 CKD. The primary outcome was sustained viral response (as a measure of efficacy); the secondary outcomes were the frequency of SAEs and drop-outs due to AEs (as measures of tolerability). The random-effects model of DerSimonian and Laird was adopted, with heterogeneity and stratified analyses.
RESULTS
Thirty clinical studies (n=1537 unique patients) were retrieved. The pooled SVR12 and SAEs rate was 0.99 (95% confidence intervals, 0.97; 1.0, I=99.8%) and 0.09 (95% CI, 0.05; 0.13, I=84.3%), respectively. The pooled SVR12 rate in studies with high HCV RNA levels at baseline was lower, 0.87 (95% CI, 0.75; 1.0, I=73.3%) (P<0.001). The pooled drop-out rate due to AEs was 0.02 (95% CI, -0.01; 0.04, I=16.1%). Common serious adverse events were anemia (n=26, 38%) and reduced eGFR (n=14, 19%). SAEs were more common in studies adopting full-dose sofosbuvir (pooled rate of SAEs 0.15, 95% CI, 0.06; 0.25; I=80.1%) and in those based on ribavirin (0.15, 95% CI, 0.07; 0.23, I=95.8%). Six studies (n=69 patients) reported eGFR levels at baseline/post- antiviral therapy; no consistent changes were found.
CONCLUSIONS
SOF-based regimens appear safe and effective in patients with stage 4-5 CKD. Serum creatinine should be carefully monitored during therapy with SOF in patients with CKD. Randomized controlled studies in order to expand our knowledge on this point are under way.
Topics: Antiviral Agents; Creatinine; Drug Therapy, Combination; Genotype; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Humans; Kidney Failure, Chronic; RNA; Renal Insufficiency, Chronic; Ribavirin; Sofosbuvir; Sustained Virologic Response
PubMed: 36165141
DOI: 10.1016/j.nefroe.2021.11.011 -
International Journal of Antimicrobial... Mar 2022This systematic review and meta-analysis examined the efficacy of sofosbuvir-based antiviral treatment against COVID-19 (coronavirus disease 2019). PubMed, Embase,... (Meta-Analysis)
Meta-Analysis
This systematic review and meta-analysis examined the efficacy of sofosbuvir-based antiviral treatment against COVID-19 (coronavirus disease 2019). PubMed, Embase, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were searched from inception to 15 August 2021. Studies comparing the clinical efficacy and safety of sofosbuvir-based antiviral regimens (study group) with other antivirals or standard of care (control group) in patients with COVID-19 were included. Overall, 687 patients with COVID-19 were included, of which 377 patients received sofosbuvir-based treatment. Mortality was lower in the study group than in the control group [odds ratio (OR) = 0.49, 95% confidence interval (CI) 0.30-0.79; I = 0%]. The overall clinical recovery rate was higher in the study group than in the control group (OR = 1.82, 95% CI 1.20-2.76; I = 28%). The study group presented a lower requirement for mechanical ventilation (OR = 0.33, 95% CI 0.13-0.89; I = 0%) and intensive care unit admission (OR = 0.42, 95% CI 0.25-0.70; I = 0%) than the control group. Furthermore, the study group exhibited a shorter hospital length of stay [mean deviation (MD), -1.49, 95% CI -2.62 to -0.37; I = 56%] and recovery time (MD, -1.34, 95% CI -2.29 to -0.38; I = 46%) than the control group. Sofosbuvir-based treatment may help reduce mortality in patients with COVID-19 and improve associated clinical outcomes. Furthermore, sofosbuvir-based treatment was as safe as the comparator in patients with COVID-19. However, further large-scale studies are warranted to validate these findings.
Topics: Humans; Intensive Care Units; Randomized Controlled Trials as Topic; Respiration, Artificial; SARS-CoV-2; Sofosbuvir; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 35134505
DOI: 10.1016/j.ijantimicag.2022.106545 -
BioMed Research International 2019Direct-acting antivirals (DAAs) are modern treatments for chronic hepatitis C infection, but majority of available evidence on its treatment effect covers genotypes 1 to... (Meta-Analysis)
Meta-Analysis
Direct-acting antivirals (DAAs) are modern treatments for chronic hepatitis C infection, but majority of available evidence on its treatment effect covers genotypes 1 to 4. Therefore, the efficacy and safety of DAAs for genotypes 5 and 6 need to be analysed. Studies were identified from Medline, Scopus, and CENTRAL and a Chinese database CNKI, from inception until Dec 4, 2018. Clinical trials were included if they enrolled patients with genotypes 5 and/or 6 infection, any type of second-generation DAAs was studied, and sustained virological response was assessed at the 12 week after treatment (SVR12) as outcome measure. Meta-analysis using statistical program was applied for pooling proportions if data were sufficient (i.e., at least 2 studies). Thirteen studies were included in the analysis. Four studies assessed the efficacy of four DAA regimens in genotype 5 patients, which were mainly sofosbuvir (SOF) plus pegylated-interferon/ribavirin (PR) or other DAAs, with SVR12 ranging from 94.4% to 100%. Twelve studies assessed the efficacy of seven DAA regimens among genotype 6 patients, but only two DAA regimens (i.e., SOF + PR and SOF/ledipasvir) had sufficient data for pooling. The pooled SVR12 rates (95% CI) were 99.6% (92.2 to 100) for SOF + PR and 99.2% (96.5 to 100) for SOF/ledipasvir. No treatment-related serious adverse event was reported, while the nonserious adverse events were comparable to other genotypes. In conclusion, DAAs are effective and may be safe for the treatment of chronic hepatitis C genotypes 5 and 6. However, our evidence is based on noncomparative studies; hence, further larger-scale randomized controlled trials in these genotypes are still required.
Topics: Antiviral Agents; Benzimidazoles; Databases, Factual; Drug Therapy, Combination; Fluorenes; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Interferons; Ribavirin; Sofosbuvir; Uridine Monophosphate
PubMed: 31815126
DOI: 10.1155/2019/2301291 -
Frontiers in Public Health 2022This study aims to systematically review recent economic evaluations of elbasvir/grazoprevir (EBR/GZR) for chronic hepatitis C (CHC), to critically appraise the...
OBJECTIVE
This study aims to systematically review recent economic evaluations of elbasvir/grazoprevir (EBR/GZR) for chronic hepatitis C (CHC), to critically appraise the reporting quality and to summarize the results.
METHODS
A literature search was undertaken using Medline, Embase, the Cochrane Library, EconLit, China National Knowledge Infrastructure, Wanfang Data, and Chongqing VIP to identify original articles containing economic evaluations of EBR/GZR for CHC published between 1 January 2000 and 31 December 2020. The Consolidated Health Economic Evaluation Reporting Standards statement was used to assess the quality of reporting of the articles.
RESULTS
Of 93 articles identified, 13 studies fulfilled the inclusion criteria. These studies were conducted in 4 countries, and 8 active interventions were assessed. The target population was patients infected with CHC genotype 1 infection in all studies. Eight out of 13 studies that compared EBR/GZR vs. other direct antiviral agents suggested that EBR/GZR was generally more cost-effective or dominant than daclatasvir/asunaprevir (DCV/ASV), sofosbuvir/velpatasvir (SOF/VEL), ledipasvir/sofosbuvir (LDV/SOF), ombitasvir/paritaprevir/ritonavir + dasabuvir (3D) but not more cost-effective than glecaprevir/pibrentasvir (GLE/PIB). Two studies from China and one study from the USA that compared EBR/GZR vs. pegylated interferon and ribavirin (PegIFN/RBV) consistently indicated that EBR/GZR was generally more cost-effective than PegIFN/RBV. One study from Italy compared EBR/GZR with SOF + PegIFN/RBV and suggested that EBR/GZR had a lower cost and higher effectiveness. One study from France and one study from the USA confirmed that compared with non-therapy for patients with chronic kidney disease, EBR/GZR was cost-effective at commonly accepted current standards. All included studies were of good quality of reporting, with an average score of 21.9 (range 19-23).
CONCLUSION
EBR/GZR for CHC genotype 1 might be cost-effective or dominant compared with PegIFN/RBV and other direct antiviral agents (SOF/VEL, 3D, DCV/ASV, LDF/SOF) or non-therapy. However, under certain assumptions, EBR/GZR was not a cost-effective alternative for CHC patients vs. GLE/PIB.
Topics: Amides; Antiviral Agents; Benzofurans; Carbamates; Cost-Benefit Analysis; Cyclopropanes; Hepacivirus; Hepatitis C, Chronic; Humans; Imidazoles; Quinoxalines; Ribavirin; Sofosbuvir; Sulfonamides
PubMed: 35646774
DOI: 10.3389/fpubh.2022.836986 -
Annals of Hepatology 2021Patients with hepatitis C virus (HCV) genotype 3 (GT3) infection are resistant to direct-acting antiviral (DAA) treatments. This study aimed to analyze the effectiveness... (Meta-Analysis)
Meta-Analysis
Patients with hepatitis C virus (HCV) genotype 3 (GT3) infection are resistant to direct-acting antiviral (DAA) treatments. This study aimed to analyze the effectiveness of sofosbuvir (SOF)+daclatasvir (DCV) ± ribavirin (RBV); SOF+velpatasvir (VEL)±RBV; SOF+VEL+voxilaprevir (VOX); and glecaprevir (GLE)+pibrentasvir (PIB) in the treatment of HCV GT3-infected patients in real-world studies. Articles were identified by searching the PubMed, EMBASE, and Cochrane Library databases from January 1, 2016 to September 10, 2019. The meta-analysis was conducted to determine the sustained virologic response (SVR) rate, using R 3.6.2 software. Thirty-four studies, conducted on a total of 7328 patients from 22 countries, met the inclusion criteria. The pooled SVR rate after 12/24 weeks of treatment was 92.07% (95% CI: 90.39-93.61%) for the evaluated regimens. Also, the SVR rate was 91.17% (95% CI: 89.23-92.94%) in patients treated with SOF+DCV±RBV; 95.08% (95% CI: 90.88-98.13%) in patients treated with SOF+VEL±RBV; 84.97% (95% CI: 73.32-93.91%) in patients treated with SOF+VEL+VOX; and 98.54% (95% CI: 96.40-99.82%) in patients treated with GLE+PIB. The pooled SVR rate of the four regimens was 95.24% (95% CI: 93.50-96.75%) in non-cirrhotic patients and 89.39% (95% CI: 86.07-92.33%) in cirrhotic patients. The pooled SVR rate was 94.41% (95% CI: 92.02-96.42%) in treatment-naive patients and 87.98% (95% CI: 84.31-91.25%) in treatment-experienced patients. The SVR rate of GLE+PIB was higher than other regimens. SOF+VEL+VOX can be used as a treatment regimen following DAA treatment failure.
Topics: Antiviral Agents; Benzimidazoles; Carbamates; Drug Combinations; Hepatitis C; Heterocyclic Compounds, 4 or More Rings; Humans; Imidazoles; Macrocyclic Compounds; Pyrrolidines; Quinoxalines; Ribavirin; Sofosbuvir; Sulfonamides; Valine
PubMed: 33059055
DOI: 10.1016/j.aohep.2020.09.012 -
Acta Bio-medica : Atenei Parmensis May 2019In literature systematic data on treatment with the fixed-dose combination of sofosbuvir and velpatasvir for 12 weeks in anti-HCV/HCV RNA positive subjects with mild... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
In literature systematic data on treatment with the fixed-dose combination of sofosbuvir and velpatasvir for 12 weeks in anti-HCV/HCV RNA positive subjects with mild fibrosis and naïve to previous Interferon free regimen are scanty. A meta-analysis has been performed to evaluate the efficacy of velpatasvir plus sofosbuvir combination in these patients.
METHODS
All randomized or non-randomized studies, investigating the sustained virological response rate to sofosbuvir plus velpatasvir without ribavirin for 12 weeks in subjects naïve to previous DAA therapy and with fibrosis F0-F2 or F0-F3, were included in the meta-analysis.
RESULTS
A total of 16 studies enrolling 4,907 subjects met the inclusion criteria and were included in this meta-analysis. The prevalence of SVR by sofosbuvir and velpatasvir was 98% (95% CI 96-99%) in the 4,907 subjects without cirrhosis. The prevalence of SVR was similar considering the 9 clinical studies and the 7 real-world studies (98%, CI 95%: 96-99% and 98%; CI 95%: 96-99%, respectively). Considering the 4 studies enrolling 1,371 subjects without advanced liver fibrosis the prevalence of SVR was also high [96% (95% CI: 94-98%)]. Data indicate a prevalence of SVR ranging to 95-100% according to the different HCV genotypes.
CONCLUSION
Sofosbuvir plus velpatasvir therapeutic regimen was highly effective in HCV patients without advanced liver disease naïve to previous DAA regimen independently the different HCV genotypes.
Topics: Antiviral Agents; Carbamates; Controlled Clinical Trials as Topic; Drug Administration Schedule; Drug Combinations; Female; Hepacivirus; Heterocyclic Compounds, 4 or More Rings; Humans; Liver Cirrhosis; Male; Prognosis; Randomized Controlled Trials as Topic; Severity of Illness Index; Sofosbuvir; Sustained Virologic Response; Treatment Outcome
PubMed: 31124995
DOI: 10.23750/abm.v90i2.8374 -
BMC Infectious Diseases Sep 2021Previous studies reported worsened lipid profiles in patients infected with hepatitis C virus (HCV) during direct-acting antivirals (DAAs) treatment. This study aimed to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous studies reported worsened lipid profiles in patients infected with hepatitis C virus (HCV) during direct-acting antivirals (DAAs) treatment. This study aimed to investigate the effect of sofosbuvir (SOF)-based DAAs on changes in low-density lipoprotein (LDL) in HCV patients.
METHODS
A systematic review of articles published before 31 May 2021 was conducted by searching MEDLINE, Cochrane Library, EMBASE, and CINAHL Plus. Eligible studies were those comparing SOF-based DAAs and non-SOF DAAs for HCV patients and providing numerical data for changes in LDL. Risk of Bias in Non-randomized Studies- of Interventions was used for assessing risk of bias, and meta-analysis was performed for changes in LDL.
RESULTS
Six studies comprising 1248 patients were included, 848 patients treated with SOF-based DAAs and 400 patients with non-SOF DAAs vs. SOF-based DAAs group had significantly greater increases in LDL from baseline to week 4 than non-SOF DAAs group (P = 0.001). However, changes in LDL from baseline to the end of treatment (P = 0.060), to post-treatment week 12 (P = 0.263), and to post-treatment week 24 (P = 0.319) did not significantly differ between the two groups. Further comparison of SOF/ledipasvir with asunaprevir/daclatasvir revealed a similar trend in changes in LDL.
CONCLUSIONS
For HCV patients, SOF-based DAA regimens were associated with rapid and significant increases in LDL during the initial 4 weeks of treatment, and the changes did not sustain after the end of treatment. Potential mechanism might be related to the phosphoramidate side chain of SOF.
Topics: Antiviral Agents; Drug Therapy, Combination; Genotype; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Humans; Lipoproteins, LDL; Ribavirin; Sofosbuvir; Sustained Virologic Response; Treatment Outcome
PubMed: 34548026
DOI: 10.1186/s12879-021-06657-9 -
Journal of Comparative Effectiveness... May 2019Hepatitis C virus (HCV) is a positive-stranded RNA virus which belongs to the family of , predominantly infecting liver hepatocytes. HCV infection is a major cause for...
Hepatitis C virus (HCV) is a positive-stranded RNA virus which belongs to the family of , predominantly infecting liver hepatocytes. HCV infection is a major cause for morbidity worldwide. The primary objective was to evaluate the comparative effectiveness of pan-genotypic therapies for the treatment of patients with HCV infection in Bulgaria. The databases MEDLINE, EMBASE, Cochrane Library, PubMed and clinicaltrials.gov were searched to identify studies evaluating the therapeutic efficacy of sofosbuvir/velpatasvir/voxilaprevir, sofosbuvir/velpatasvir and glecaprevir/pibrentasvir for the treatment of HCV patients. The range of sustained virologic response rates among all genotypes achieved after therapy with sofosbuvir/velpatasvir/voxilaprevir was 92-100% (8-week therapy) in treatment-naive patients and 99-100% (12-week therapy) in experienced patients. The range of sustained virologic response rates with glecaprevir/pibrentasvir was 91-100% (12-week therapy) and 97-100% (12-week therapy) with sofosbuvir/velpatasvir. Sofosbuvir/velpatasvir/voxilaprevir is a noninferior therapy offering a simple and short-term treatment regimen with high efficacy, favorable safety profile and good tolerability.
Topics: Aminoisobutyric Acids; Antiviral Agents; Bulgaria; Carbamates; Cyclopropanes; Drug Therapy, Combination; Genotype; Hepacivirus; Hepatitis C, Chronic; Heterocyclic Compounds, 4 or More Rings; Humans; Lactams, Macrocyclic; Leucine; Macrocyclic Compounds; Proline; Quinoxalines; Sofosbuvir; Sulfonamides; Sustained Virologic Response
PubMed: 30920311
DOI: 10.2217/cer-2018-0143