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Journal of Medical Virology Apr 2023At present, there are some differences in the research results of nirmatrelvir-ritonavir compared with other antiviral drugs for the treatment of COVID-19 patients. We... (Comparative Study)
Comparative Study Meta-Analysis
At present, there are some differences in the research results of nirmatrelvir-ritonavir compared with other antiviral drugs for the treatment of COVID-19 patients. We aimed to evaluate the efficacy and safety of nirmatrelvir-ritonavir compared with other antiviral drugs and the impact of different antiviral drugs on the short- and long-term effects of COVID-19. PubMed, Embase, CENTRAL (Cochrane Central Register of Controlled Trials), Web of Science, Google Scholar, and MedRxiv were searched to identify relevant studies from inception to March 30, 2023. We conducted a meta-analysis to estimate the effects of nirmatrelvir-ritonavir compared with other antiviral drugs for the treatment of COVID-19 patients and safety outcomes. The RoB1 and ROBINS-I were used to assess the bias risk of the included studies. Revman 5.4 software was used for meta-analysis (PROSPERO Code No: CRD42023397816). Twelve studies were included, including 30 588 COVID-19 patients, of whom 13 402 received nirmatrelvir-ritonavir. The meta-analysis results showed that the nirmatrelvir-ritonavir group had a lower proportion of patients than the control group in terms of long-term mortality (odds ratio [OR] = 0.29, 95% confidence interval [CI]: 0.13-0.66), hospitalization (OR = 0.44, 95% CI: 0.37-0.53, short term; OR = 0.52, 95% CI: 0.36-0.77, long term), and disease progression (OR = 0.56, 95% CI: 0.38-0.83, short term; OR = 0.60, 95% CI: 0.48-0.74, long term), and nirmatrelvir ritonavir showed little difference in safety compared to the control group. Nirmatrelvir-ritonavir can reduce the mortality and hospitalization of COVID-19 patients compared with other antiviral drugs. Further large-scale studies remain to validate these findings.
Topics: Antiviral Agents; COVID-19 Drug Treatment; Drug Combinations; Lactams; Leucine; Nitriles; Proline; COVID-19; Humans
PubMed: 37183808
DOI: 10.1002/jmv.28732 -
The Journal of Infectious Diseases Aug 2022Since the widespread adoption of palivizumab prophylaxis in Europe, there have been a number of clinical practice guidelines (CPGs) published for the prevention of...
BACKGROUND
Since the widespread adoption of palivizumab prophylaxis in Europe, there have been a number of clinical practice guidelines (CPGs) published for the prevention of respiratory syncytial virus (RSV) infection in children. The aim of this systematic review was to identify CPGs for the prevention of RSV infection across Europe.
METHODS
We performed a systematic literature search and contacted European influenza and respiratory virus networks and public health institutions, to identify national CPGs for the prevention of RSV infection. The Reporting Items for practice Guidelines in Healthcare (RIGHT) Statement checklist was applied to extract data and review the quality of reporting.
RESULTS
A total of 20 national CPGs were identified, all published between 2000 and 2018. The greatest discrepancy between guidelines was the recommendations for palivizumab prophylaxis for premature infants, with recommendations varying by gestational age. All guidelines recommended or considered the use of palivizumab in infants with bronchopulmonary dysplasia, 85% (n = 17) in children with congenital heart disease (CHD), and 60% (n = 12) in children with severe combined immunodeficiency.
CONCLUSIONS
We recommend that agencies publishing RSV prevention guidelines adopt the RIGHT reporting requirements when updating these guidelines to improve the presentation of the evidence-base for decisions.
Topics: Antibodies, Monoclonal, Humanized; Antiviral Agents; Child; Hospitalization; Humans; Infant; Infant, Newborn; Palivizumab; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses
PubMed: 35333332
DOI: 10.1093/infdis/jiac059 -
Viruses Nov 2023Acute hepatitis B infection is associated with severe liver disease and chronic sequelae in some cases. The purpose of this review was to determine the efficacy of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acute hepatitis B infection is associated with severe liver disease and chronic sequelae in some cases. The purpose of this review was to determine the efficacy of nucleoside analogues (NA) (lamivudine versus entecavir) compared to placebo or no intervention for treating acute primary HBV infection.
METHODS
A meta-analysis for drug intervention was performed, following a fixed-effect model. Randomized controlled trials (RCTs) and quasi-randomized studies that evaluated the outcomes of NA in acute hepatitis B infection were included. The following outcomes were considered: virological cure (PCR negative), elimination of acute infection (seroconversion of HBsAg), mortality, and serious adverse events.
RESULTS
Five trials with 627 adult participants with severe acute hepatitis B defined by biochemical and serologic parameters were included. Virological cure did not favor any intervention: OR 0.96, 95% CI 0.54 to 1.7 ( = 0.90), I2 = 58%. Seroconversion of HBsAg to negative favored placebo/standard-of-care compared to lamivudine: OR 0.54, 95% CI 0.33 to 0.9 ( = 0.02), I2 = 31%. The only trial that compared entecavir and lamivudine favored entecavir over lamivudine (OR: 3.64, 95% CI 1.31-10.13; 90 participants). Adverse events were mild.
CONCLUSION
There is insufficient evidence that NA obtain superior efficacy compared with placebo/standard-of-care in patients with acute viral hepatitis, based on low quality evidence.
Topics: Adult; Humans; Lamivudine; Antiviral Agents; Hepatitis B Surface Antigens; Hepatitis B; Hepatitis B virus; Hepatitis B, Chronic; Treatment Outcome; DNA, Viral
PubMed: 38005918
DOI: 10.3390/v15112241 -
Medicina (Kaunas, Lithuania) Mar 2023: The study of clinical pharmacokinetics of inhaled antivirals is particularly important as it helps one to understand the therapeutic efficacy of these drugs and how... (Review)
Review
: The study of clinical pharmacokinetics of inhaled antivirals is particularly important as it helps one to understand the therapeutic efficacy of these drugs and how best to use them in the treatment of respiratory viral infections such as influenza and the current COVID-19 pandemic. The article presents a systematic review of the available pharmacokinetic data of inhaled antivirals in humans, which could be beneficial for clinicians in adjusting doses for diseased populations. : This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. A comprehensive literature search was conducted using multiple databases, and studies were screened by two independent reviewers to assess their eligibility. Data were extracted from the eligible studies and assessed for quality using appropriate tools. : This systematic review evaluated the pharmacokinetic parameters of inhaled antiviral drugs. The review analyzed 17 studies, which included Zanamivir, Laninamivir, and Ribavirin with 901 participants, and found that the non-compartmental approach was used in most studies for the pharmacokinetic analysis. The outcomes of most studies were to assess clinical pharmacokinetic parameters such as the Cmax, AUC, and t1/2 of inhaled antivirals. : Overall, the studies found that the inhaled antiviral drugs were well tolerated and exhibited favorable pharmacokinetic profiles. The review provides valuable information on the use of these drugs for the treatment of influenza and other viral respiratory infections.
Topics: Humans; Antiviral Agents; Influenza, Human; Pandemics; COVID-19; Zanamivir
PubMed: 37109600
DOI: 10.3390/medicina59040642 -
Antiviral Research Jan 2024Remdesivir, molnupiravir, and nirmatrelvir/ritonavir are three antiviral agents approved by FDA emergency authorization for treating mild to moderate symptomatic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Remdesivir, molnupiravir, and nirmatrelvir/ritonavir are three antiviral agents approved by FDA emergency authorization for treating mild to moderate symptomatic COVID-19 adult outpatients at high risk for hospitalization and death.
OBJECTIVES
To compare the efficacy and safety of these antivirals based on updated published RCT and real-world data.
STUDY DESIGN
This systematic review followed the preferred reporting items for systematic reviews and meta-analysis framework guidelines. We searched all publications up to January 2023. RRs and 95% CIs for death, hospitalization, and adverse events were calculated.
RESULTS
Six RCTs and seven cohort studies were included, with 1,456,523 participants, of whom 50,979 were treated with antivirals. Remdesivir was associated with the lowest probability of hospitalization and death compared to nirmatrelvir/ritonavir and molnupiravir (P-scores 0.99 and 0.90, respectively, for remdesivir, 0.64 and 0.55, respectively for nirmatrelvir/ritonavir, and 0.26 and 0.49, respectively for molnupiravir). Based on indirect comparisons, remdesivir was associated with a statistically significant decreased risk for hospitalization compared to molnupiravir (RR 0.09; 95% CI 0.02-0.40) and to nirmatrelvir/ritonavir (RR 0.11; 95% CI 0.03-0.73). No statistically significant difference was found between antivirals in the mortality risk reduction and the risk for side effects.
CONCLUSIONS
This is the most comprehensive network meta-analysis integrating RCTs and real-world data. In our indirect comparison, remdesivir was associated with the highest efficacy in preventing hospitalization among high risk symptomatic COVID-19 outpatients, compared to nirmatrelvir/ritonavir and molnupiravir. This finding supports current guidelines, and may have importance when deciding which antiviral to use, together with other important factors.
Topics: Adult; Humans; COVID-19; Network Meta-Analysis; Outpatients; Ritonavir; Antiviral Agents; Hydroxylamines; Cytidine; Nitriles; Lactams; Proline; Leucine
PubMed: 38056602
DOI: 10.1016/j.antiviral.2023.105768 -
Viruses Jun 2023About 5% of chronic hepatitis C (CHC) patients experienced treatment failure with direct-acting antiviral (DAA) treatment. The global data on the practice and treatment... (Meta-Analysis)
Meta-Analysis Review
About 5% of chronic hepatitis C (CHC) patients experienced treatment failure with direct-acting antiviral (DAA) treatment. The global data on the practice and treatment outcomes of Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX) in DAA-experienced CHC patients remains sparse. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of SOF/VEL/VOX as a salvage treatment in DAA-experienced CHC patients. We searched five electronic databases from inception to 31 January 2023. The study outcomes were SVR12 and treatment-related adverse effects, with subgroup analysis performed based on genotype, cirrhosis, HCC, prior SOF/VEL exposure, and region. We identified and analyzed data from 24 studies (2877 DAA-experienced CHC patients); 17.2% had prior SOF/VEL exposure, 25% received ribavirin with SOF/VEL/VOX, and 42% had pre-treatment resistance-associated substitution (RAS) testing performed. Eastern Mediterranean had a higher pooled SVR12 than the America and Europe regions ( < 0.05). Predictors of SOF/VEL/VOX failure were genotype 3, active HCC, baseline cirrhosis, and prior SOF/VEL. Baseline RAS mutation and ribavirin supplementation were not associated with higher SVR12. Treatment discontinuation because of drug-related adverse events was uncommon (10 studies, 0.2%). In summary, SOF/VEL/VOX is efficacious and safe for retreatment in DAA-experienced CHC patients, even with RAS mutation. Our findings support SOF/VEL/VOX as a first-line rescue treatment for DAA-experienced CHC patients.
Topics: Humans; Antiviral Agents; Sofosbuvir; Hepacivirus; Hepatitis C, Chronic; Ribavirin; Carcinoma, Hepatocellular; Sustained Virologic Response; Liver Neoplasms; Treatment Outcome; Hepatitis C; Genotype; Drug Therapy, Combination
PubMed: 37515176
DOI: 10.3390/v15071489 -
Journal of Hepatology Apr 2023Hepatitis B core-related antigen (HBcrAg) is a new biomarker for chronic hepatitis B (CHB) whose performance has not been critically or systematically appraised. Herein,...
BACKGROUND & AIMS
Hepatitis B core-related antigen (HBcrAg) is a new biomarker for chronic hepatitis B (CHB) whose performance has not been critically or systematically appraised. Herein, we performed a systematic review to determine its clinical utility.
METHODS
We evaluated the biological pathway of HBcrAg and performed a systematic review of PubMed for clinical trials, cohort studies, and case-control studies that evaluated the clinical utility of HBcrAg. The effectiveness of HBcrAg in predicting HBV-specific clinical events (e.g. HBeAg seroconversion, phases of CHB, HBsAg loss, treatment response, and relapse after stopping therapy) was examined using receiver-operating characteristic curves. The correlation coefficients of HBcrAg with HBV DNA, quantitative HBsAg (qHBsAg), HBV RNA, and cccDNA were summarised from published studies. Median values were used as estimates.
RESULTS
HBcrAg consists of three precore/core protein products: HBcAg, HBeAg, and a 22 kDa precore protein. HBcrAg assays have been associated with false-positive rates of 9.3% and false-negative rates of between 12-35% for CHB. The new iTACT-HBcrAg is more sensitive but does not reduce the false-positive rate. A PubMed search found 248 papers on HBcrAg, of which 59 were suitable for analysis. The clinical performance of HBcrAg was evaluated using AUROC analyses, with median AUROCs of 0.860 for HBeAg seroconversion, 0.867 for predicting HBeAg(-) hepatitis, 0.645 for HBsAg loss, 0.757 for treatment response, and 0.688 for relapse after stopping therapy. The median correlation coefficient (r) was 0.630 with HBV DNA, 0.414 with qHBsAg, 0.619 with HBV RNA and 0.550 with cccDNA. Correlation decreased during antiviral therapy, but combined biomarkers improved performance.
CONCLUSIONS
HBcrAg has a mixed performance and has a poor correlation with HBsAg loss and antiviral therapy, hence HBcrAg results should be interpreted with caution.
IMPACT AND IMPLICATIONS
Hepatitis B core-related antigen (HBcrAg) has been used to assess management of patients with chronic hepatitis B (CHB) without a systematic and critical Sreview of its performance. Our finding that HBcrAg had a false-positive rate of 9% and a false-negative rate of 12-35% raises concerns, although larger studies are needed for validation. A systematic review showed that the performance of HBcrAg was variable depending on the CHB endpoint; it was excellent at predicting HBeAg seroconversion and HBeAg-negative chronic hepatitis (vs. chronic infection), which should be its main use, but it was poor for relapse after stopping antiviral therapy and for HBsAg loss. HBcrAg results should be interpreted with considerable caution, particularly by physicians, researchers, guideline committees and agencies that approve diagnostic tests.
Topics: Humans; Hepatitis B Core Antigens; Hepatitis B, Chronic; Hepatitis B Surface Antigens; Hepatitis B e Antigens; DNA, Viral; Biomarkers; Antiviral Agents; RNA; Hepatitis B virus
PubMed: 36586590
DOI: 10.1016/j.jhep.2022.12.017 -
Reviews in Medical Virology Jan 2024This review assesses the antiviral potential of melatonin through comprehensive analysis of studies across human subjects, animal models, cell cultures, and in-silico... (Review)
Review
This review assesses the antiviral potential of melatonin through comprehensive analysis of studies across human subjects, animal models, cell cultures, and in-silico simulations. The search strategy targeted relevant research until 22 June 2023, resulting in 20 primary studies after screening and deduplication. The findings highlight strong evidence supporting antiviral properties of melatonin. In silico studies identify melatonin as a candidate against SARS-CoV-2, reducing cytokine storm-related respiratory responses. Cell culture experiments reveal its multifaceted effects on different viruses including respiratory syncytial virus, anti-dengue virus, transmissible gastroenteritis virus, and encephalomyocarditis virus. Animal studies show melatonin reduces mortality and viral replication in various infections such as Venezuelan equine encephalomyelitis and COVID-19. Clinical trials show how it could be evaluated, but with no conclusive evidence of efficacy and safety so far from large, double-blind placebo-controlled trials. These insights showcase the potential of melatonin as a versatile antiviral agent with immunomodulatory, antioxidant, anti-inflammatory and antiviral properties. In summary, our review highlights melatonin's promising antiviral properties across diverse settings. Melatonin's immunomodulatory and antiviral potential makes it a compelling candidate for further investigation, emphasising the need for rigorous clinical trials to establish its safety and efficacy against viral infections.
Topics: Animals; Humans; Antiviral Agents; COVID-19; Melatonin; Randomized Controlled Trials as Topic; SARS-CoV-2; Virus Diseases
PubMed: 38126924
DOI: 10.1002/rmv.2499 -
Zeitschrift Fur Naturforschung. C,... Sep 2023Suppressors of cytokine signaling (SOCSs) are implicated in viral infection and host antiviral innate immune response. Recent studies demonstrate that viruses can hijack... (Review)
Review
Suppressors of cytokine signaling (SOCSs) are implicated in viral infection and host antiviral innate immune response. Recent studies demonstrate that viruses can hijack SOCSs to inhibit Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway, block the production and signaling of interferons (IFNs). At the same time, viruses can hijack SOCS to regulate non-IFN factors to evade antiviral response. Host cells can also regulate SOCSs to resist viral infection. The competition of the control of SOCSs may largely determine the fate of viral infection and the susceptibility or resistance of host cells, which is of significance for development of novel antiviral therapies targeting SOCSs. Accumulating evidence reveal that the regulation and function of SOCSs by viruses and host cells are very complicated, which is determined by characteristics of both viruses and host cell types. This report presents a systematic review to evaluate the roles of SOCSs in viral infection and host antiviral responses. One of messages worth attention is that all eight SOCS members should be investigated to accurately characterize their roles and relative contribution in each viral infection, which may help identify the most effective SOCS to be used in "individualized" antiviral therapy.
Topics: Humans; Virus Diseases; Antiviral Agents; Signal Transduction; Immunity, Innate
PubMed: 37233326
DOI: 10.1515/znc-2023-0024 -
Survey of Ophthalmology 2024Acute retinal necrosis is a progressive intraocular inflammatory syndrome characterized by diffuse necrotizing retinitis that can lead to a poor visual outcome, mainly... (Meta-Analysis)
Meta-Analysis Review
Acute retinal necrosis is a progressive intraocular inflammatory syndrome characterized by diffuse necrotizing retinitis that can lead to a poor visual outcome, mainly from retinal detachment. The antiviral treatment approach for acute retinal necrosis varies as there are no established guidelines. We summarize the outcomes of acute retinal necrosis with available antiviral treatments. Electronic searches were conducted in PubMed/MEDLINE, EMBASE, Scopus, and Google Scholar for interventional and observational studies. Meta-analysis was performed to evaluate the pooled proportion of the predefined selected outcomes. This study was registered in PROSPERO (CRD42022320987). Thirty-four studies with a total of 963 participants and 1,090 eyes were included in the final analysis. The estimated varicella-zoster virus and herpes simplex virus polymerase chain reaction-positive cases were 63% (95% CI: 55-71%) and 35% (95% CI: 28-42%), respectively. The 3 main antiviral treatment approaches identified were oral antivirals alone, intravenous antivirals alone, and a combination of systemic (oral or intravenous) and intravitreal antivirals. The overall pooled estimated proportions of visual acuity improvement, recurrence, and retinal detachment were 37% (95% CI: 27-47%), 14% (95% CI: 8-21%), and 43% (95% CI: 38-50%), respectively. Patients treated with systemic and intravitreal antivirals showed a trend towards better visual outcomes than those treated with systemic antivirals (oral or intravenous) alone, even though this analysis was not statistically significant (test for subgroup differences P = 0.83).
Topics: Humans; Retinal Necrosis Syndrome, Acute; Antiviral Agents; Acyclovir; Eye Infections, Viral; Retinal Detachment; Retrospective Studies
PubMed: 37774799
DOI: 10.1016/j.survophthal.2023.09.004