Meta-Analysis Review

Ribavirin treatment for respiratory syncytial virus infection in patients with haematologic malignancy and haematopoietic stem cell transplant recipients: a systematic review and meta-analysis.

Authors: Kasama Manothummetha, Thanuthong Mongkolkaew, Punyot Tovichayathamrong...

BACKGROUND

Ribavirin use for respiratory syncytial virus (RSV) infection in patients with haematologic malignancies (HM) and haematopoietic stem cell transplant (HSCT) recipients remains controversial.

OBJECTIVES

To summarize the current evidence of ribavirin treatment in association with mortality and progression to lower respiratory tract infection (LRTI) among patients with HM/HSCT with RSV infection.

DATA SOURCES

MEDLINE, Embase, and the Institute for Scientific Information Web of Science.

STUDY ELIGIBILITY CRITERIA

Randomized controlled trials and observational studies investigating the effects of ribavirin, compared with treatment without ribavirin, for RSV infection.

PARTICIPANTS

Patients with HM/HSCT.

INTERVENTIONS

Ribavirin versus no ribavirin.

ASSESSMENT OF RISK OF BIAS

The risk of bias in non-randomized studies of exposure (ROBIN-E).

METHODS OF DATA SYNTHESIS

The random-effects model was used to calculate the pooled OR (pOR) with 95% CI for the pooled effect estimates of ribavirin benefits. Grading of recommendation assessment, development, and evaluation was used to evaluate the certainty of evidence.

RESULTS

One randomized controlled trial and 14 observational studies were included, representing 1125 patients with HM/HSCT. Ribavirin use was not associated with lower all-cause or RSV-associated mortality with pORs [95% CI] of 0.81 [0.40, 1.66], I = 55% (low certainty of evidence) and 0.48 [0.11, 2.15], I = 64% (very low certainty of evidence), respectively. In subgroup analyses, ribavirin use was associated with lower mortality in patients with HM/HSCT with LRTI with pOR [95% CI] of 0.19 [0.07, 0.51], I = 0% (moderate certainty of evidence). In subgroup analyses among studies providing adjusted OR, ribavirin use was associated with lower all-cause mortality with pOR of 0.41 [0.23, 0.74], I = 0% (moderate certainty of evidence). In addition, aerosolized ribavirin was associated with lower progression to LRTI with pOR [95% CI] of 0.27 [0.09, 0.80], I = 71% (low certainty of evidence).

CONCLUSIONS

Ribavirin may be a reasonable option to treat RSV in patients with HM/HSCT in the absence of other effective antiviral agents.

Topics: Humans; Ribavirin; Respiratory Syncytial Virus Infections; Antiviral Agents; Hematologic Neoplasms; Respiratory Tract Infections; Hematopoietic Stem Cell Transplantation

PubMed: 37116860
DOI: 10.1016/j.cmi.2023.04.021

Randomized Controlled Trial

Authors: Lars Krogvold, Ida Maria Mynarek, Erica Ponzi...

Previous studies showed a low-grade enterovirus infection in the pancreatic islets of patients with newly diagnosed type 1 diabetes (T1D). In the Diabetes Virus Detection (DiViD) Intervention, a phase 2, placebo-controlled, randomized, parallel group, double-blind trial, 96 children and adolescents (aged 6-15 years) with new-onset T1D received antiviral treatment with pleconaril and ribavirin (n = 47) or placebo (n = 49) for 6 months, with the aim of preserving β cell function. The primary endpoint was the mean stimulated C-peptide area under the curve (AUC) 12 months after the initiation of treatment (less than 3 weeks after diagnosis) using a mixed linear model. The model used longitudinal log-transformed serum C-peptide AUCs at baseline, at 3 months, 6 months and 1 year. The primary endpoint was met with the serum C-peptide AUC being higher in the pleconaril and ribavirin treatment group compared to the placebo group at 12 months (average marginal effect = 0.057 in the linear mixed model; 95% confidence interval = 0.004-0.11, P = 0.037). The treatment was well tolerated. The results show that antiviral treatment may preserve residual insulin production in children and adolescent with new-onset T1D. This provides a rationale for further evaluating antiviral strategies in the prevention and treatment of T1D. European Union Drug Regulating Authorities Clinical Trials identifier: 2015-003350-41 .

Topics: Child; Adolescent; Humans; Diabetes Mellitus, Type 1; Ribavirin; C-Peptide; Double-Blind Method; Antiviral Agents

PubMed: 37789144
DOI: 10.1038/s41591-023-02576-1

Review

Authors: Volker Kinast, Thomas L Burkard, Daniel Todt...

Hepatitis E virus (HEV) is an underestimated disease, leading to estimated 20 million infections and up to 70,000 deaths annually. Infections are mostly asymptomatic but can reach mortality rates up to 25% in pregnant women or become chronic in immunocompromised patients. The current therapy options are limited to the unspecific antivirals Ribavirin (RBV) and pegylated Interferon-α (pegIFN-α). RBV leads to viral clearance in only 80% of patients treated, and is, similar to pegIFN-α, contraindicated in the major risk group of pregnant women, emphasizing the importance of new therapy options. In this review, we focus on the urgent need and current efforts in HEV drug development. We provide an overview of the current status of HEV antiviral research. Furthermore, we discuss strategies for drug development and the limitations of the approaches with respect to HEV.

Topics: Antiviral Agents; Drug Development; Drug Therapy, Combination; Female; Hepatitis E; Humans; Immunocompromised Host; Interferon-alpha; Pregnancy; Ribavirin

PubMed: 31141919
DOI: 10.3390/v11060485

Authors: Heiner Wedemeyer, Sven Pischke

Topics: Female; Hepatitis E; Humans; Male; Research Design; Ribavirin

PubMed: 25869341
DOI: 10.3238/arztebl.2015.0220b

Review

Authors: Katherine L B Borden

Cancer cells rapidly evolve a multitude of defense mechanisms to evade the effects of the oncologist's drug arsenal. Unfortunately, clinical strategies to overcome these lag far behind. This mismatch likely underlies our inability to implement new durable treatment strategies. Here, a new form of multidrug resistance, inducible drug glucuronidation, is discussed. This form was discovered while developing means to target a specific oncogene, the eukaryotic translation initiation factor 4E (eIF4E), with its inhibitor ribavirin. In two clinical studies, ribavirin treatment led to substantial clinical responses, but all responding patients eventually relapsed. In most cases, this was due to the overexpression of the sonic hedgehog transcription factor Gli1, which elevated the UDP glucuronsyltransferase UGT1A enzymes. UGT1As add glucuronic acid to many drugs. Indeed, these cells are resistant to not only ribavirin, but also Ara-C, and likely other drugs. Inhibition of Gli1 reduced UGT1As, eliminated drug glucuronides, and renewed sensitivity to ribavirin and Ara-C. These studies highlight that cancer cells and their resistant counterparts metabolize drugs differently from each other as well as from normal cells. Likely, these inducible modifications go beyond glucuronidation. Understanding the extent of inducible drug modifications and the pathways that drive expression of the corresponding enzymatic machinery will better position us to finally make resistance futile.

Topics: Drug Resistance, Neoplasm; Eukaryotic Initiation Factor-4E; Glucuronic Acid; Glucuronosyltransferase; Humans; Neoplasms; Ribavirin; Transcription Factors; Zinc Finger Protein GLI1

PubMed: 25477336
DOI: 10.1158/0008-5472.CAN-14-2607

Authors: Didier Samuel

Topics: Antineoplastic Agents; Antiviral Agents; Carcinoma, Hepatocellular; Drug Delivery Systems; Drug Therapy, Combination; Genotype; Hepacivirus; Hepatitis C; Humans; Liver Neoplasms; Ribavirin; Treatment Outcome

PubMed: 19923033
DOI: 10.1016/j.jhep.2009.10.017

Meta-Analysis

Authors: Önder Ergönül, Şiran Keske, Melis Gökçe Çeldir...

We performed a systematic review and meta-analysis on the effectiveness of ribavirin use for the prevention of infection and death of healthcare workers exposed to patients with Crimean-Congo hemorrhagic fever virus (CCHFV) infection. Splashes with blood or bodily fluids (odds ratio [OR] 4.2), being a nurse or physician (OR 2.1), and treating patients who died from CCHFV infection (OR 3.8) were associated with healthcare workers acquiring CCHFV infection; 7% of the workers who received postexposure prophylaxis (PEP) with ribavirin and 89% of those who did not became infected. PEP with ribavirin reduced the odds of infection (OR 0.01, 95% CI 0-0.03), and ribavirin use <48 hours after symptom onset reduced the odds of death (OR 0.03, 95% CI 0-0.58). The odds of death increased 2.4-fold every day without ribavirin treatment. Ribavirin should be recommended as PEP and early treatment for workers at medium-to-high risk for CCHFV infection.

Topics: Antiviral Agents; Global Health; Health Personnel; Hemorrhagic Fever Virus, Crimean-Congo; Hemorrhagic Fever, Crimean; Humans; Post-Exposure Prophylaxis; Ribavirin

PubMed: 30124196
DOI: 10.3201/eid2409.171709

Review

Authors: Emmanuel Thomas, Marc G Ghany, T Jake Liang...

Ribavirin has been used as an antiviral agent for several decades. Although it has activity against numerous viruses, its major use clinically has been in the treatment of respiratory syncytial virus in paediatric patients and chronic HCV infection in both children and adults. This review highlights the clinical application and mechanism of action of ribavirin and discusses the future role of ribavirin in treatment of HCV where there are intense research efforts to improve therapy.

Topics: Animals; Antiviral Agents; Hepatitis C; Humans; Ribavirin

PubMed: 22592135
DOI: 10.3851/IMP2125

Authors: B Bannister

Topics: Animals; Cross Infection; Humans; Lassa Fever; Ribavirin

PubMed: 1995110
DOI: 10.1136/bmj.302.6768.114-b

Authors: Andrew B Janowski, Holly Dudley, David Wang...

BACKGROUND

Recent recognition of invasive astrovirus infections, including encephalitis and viremia in humans, have highlighted the need for effective anti-astrovirus therapeutics. However, there is a paucity of data regarding the in vitro activity of broad-spectrum RNA antivirals against astroviruses, including ribavirin and favipiravir.

OBJECTIVES

We quantified the EC50 values for ribavirin and favipiravir against two human astrovirus strains, astrovirus VA1 (VA1) and human astrovirus 4 (HAstV4).

STUDY DESIGN

Caco-2 cells were infected with VA1 or HAstV4 in the presence of ribavirin or favipiravir (dose range 0.1-1000 μM), and the cells were maintained in media containing the drugs for 72 h. Viral RNA was extracted and quantified by qRT-PCR. As a surrogate for cytotoxicity, cellular adenosine triphosphate (ATP) from each drug treatment was also measured.

RESULTS

VA1 replication was inhibited 10-100-fold by both ribavirin (EC50 = 154 μM) and favipiravir (EC50 = 246 μM). In contrast, ribavirin inhibited HAstV4 replication (EC50 = 268 μM) but favipiravir only reduced replication by 44% at the highest dose. Mild reductions in ATP (17-31%) was only observed at the highest concentration of ribavirin (1000 μM) and no significant decrease in ATP was detected for any concentration of favipiravir.

CONCLUSIONS

Ribavirin inhibited both human astrovirus species and favipiravir was only active against VA1. In the future, the in vivo efficacy of these drugs could be tested with development of an animal model of human astrovirus infection.

Topics: Amides; Antiviral Agents; Caco-2 Cells; Humans; Mamastrovirus; Pyrazines; Ribavirin; Virus Replication

PubMed: 31864069
DOI: 10.1016/j.jcv.2019.104247