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PloS One 2022Efforts are ongoing by researchers globally to develop new drugs or repurpose existing ones for treating COVID-19. Thus, this led to the use of oseltamivir, an antiviral... (Meta-Analysis)
Meta-Analysis
Efforts are ongoing by researchers globally to develop new drugs or repurpose existing ones for treating COVID-19. Thus, this led to the use of oseltamivir, an antiviral drug used for treating influenza A and B viruses, as a trial drug for COVID-19. However, available evidence from clinical studies has shown conflicting results on the effectiveness of oseltamivir in COVID-19 treatment. Therefore, this systematic review and meta-analysis was performed to assess the clinical safety and efficacy of oseltamivir for treating COVID-19. The study was conducted according to the PRISMA guidelines, and the priori protocol was registered in PROSPERO (CRD42021270821). Five databases were searched, the identified records were screened, and followed by the extraction of relevant data. Eight observational studies from four Asian countries were included. A random-effects model was used to pool odds ratios (ORs), mean differences (MD), and their 95% confidence intervals (CI) for the study analysis. Survival was not significantly different between all categories of oseltamivir and the comparison groups analysed. The duration of hospitalisation was significantly shorter in the oseltamivir group following sensitivity analysis (MD -5.95, 95% CI -9.91--1.99 p = 0.003, heterogeneity I2 0%, p = 0.37). The virological, laboratory and radiological response rates were all not in favour of oseltamivir. However, the electrocardiographic safety parameters were found to be better in the oseltamivir group. However, more studies are needed to establish robust evidence on the effectiveness or otherwise of oseltamivir usage for treating COVID-19.
Topics: Humans; Oseltamivir; Antiviral Agents; Influenza, Human; COVID-19 Drug Treatment
PubMed: 36454880
DOI: 10.1371/journal.pone.0277206 -
The World Allergy Organization Journal Feb 2023Omalizumab which downregulates the immunoglobulin E (IgE) receptor site on plasmacytoid dendritic cells and thereby increases interferon-α (INF-α) production, may... (Review)
Review
Omalizumab which downregulates the immunoglobulin E (IgE) receptor site on plasmacytoid dendritic cells and thereby increases interferon-α (INF-α) production, may shorten the duration of viral infections by enhancing the antiviral immunity. A systematic review was conducted to investigate whether previous anti-IgE treatment with omalizumab could protect against SARS-CoV-2 disease ("COVID-19") (infection, disease duration, and severity), and whether IFN-α upregulation could be involved. The research included articles published from March 2020 to January 2022. An accurate search was performed on bibliographic biomedical database (MEDLINE - Pubmed, SCOPUS, EMBASE, BIOMED CENTRAL, Google scholar, COCHRANE LIBRARY, ClinicalTrial.gov) including cohorts, case reports and reviews. Different methods were used, based on the study design, to assess the quality of eligible studies. Several authors link omalizumab to a possible protection against viruses, but they often refer to studies carried out before the pandemic and with viruses other than SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) (eg, rhinoviruses -RV). Few cases of COVID-19 patients treated with omalizumab have been recorded, and, in most of them, no increased susceptibility to severe disease was observed. According to these data, the current indication is to continue omalizumab therapy during the pandemic. Moreover, although omalizumab may enhance the antiviral immune response even for SARS-CoV-2, further studies are needed to confirm this hypothesis. It would be helpful to establish a registry of omalizumab-treated (or in treatment) patients who have developed COVID-19. Finally, randomized controlled trials could be able to demonstrate the effect of omalizumab in protecting against severe SARS-CoV-2, through IFN-α upregulation or other immunological pathways.
PubMed: 36644451
DOI: 10.1016/j.waojou.2023.100741 -
Reviews in Medical Virology Jan 2022It has been demonstrated that lactoferrin (LF) plays a role in host defence, but evidence on its potential antiviral property from clinical studies is fragmented. Our... (Review)
Review
It has been demonstrated that lactoferrin (LF) plays a role in host defence, but evidence on its potential antiviral property from clinical studies is fragmented. Our systematic review aimed at identifying the effects of orally administered LF against virus infections. The systematic search was conducted on PubMed, Scopus, Web of Science, BioRxiv.org and ClinicalTrials.gov from database inception to 7th January 2021. Eligible articles investigated any virus family and provided data on the effects of orally administered LF of any origin in the prevention and/or management of confirmed viral infections in people of any age. A narrative synthesis of the results was performed. Quality was assessed with the Cochrane Risk-Of-Bias and ROBINS-1 tools. A total of 27 records were included, nine of which were registered protocols. We found data on Flaviviridae (n = 10), Retroviridae (n = 3), Coronaviridae (n = 2), Reoviridae (n = 2) and Caliciviridae (n = 1). Most published trials were at high risk of bias. The findings were heterogeneous across and within viral families regarding virological, immunological and biological response, with no clear conclusion. Some weak but positive results were reported about decrease of symptom severity and duration, or reduction in viral loads. Despite high tolerability, the effects of LF as oral supplement are still inconsistent, both in preventing and managing viral infections. Small sample sizes, variety in recruitment and treatment protocols, and low study quality may have contributed to such heterogeneity. Better-designed studies are needed to further investigate its potential benefits against viral infections, including SARS-CoV-2.
Topics: Anti-Infective Agents; COVID-19; Humans; Lactoferrin; SARS-CoV-2; Virus Diseases
PubMed: 34133812
DOI: 10.1002/rmv.2261 -
The Cochrane Database of Systematic... Jul 2014PRO 140 (a humanized form of the PA14 antibody, a monoclonal CCR5 antibody) inhibits CCR5-tropic (R5) type 1 human immunodeficiency virus (HIV). This may be an effective... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
PRO 140 (a humanized form of the PA14 antibody, a monoclonal CCR5 antibody) inhibits CCR5-tropic (R5) type 1 human immunodeficiency virus (HIV). This may be an effective new treatment with the potential to address the limitations of currently available therapies for HIV-infected patients.
OBJECTIVES
We aimed to assess the efficacy, safety, clinical disease progression and immunologic (CD4 count/percentage) and virologic (plasma HIV RNA viral load) markers of PRO 140 for HIV-infected patients in randomized controlled trials (RCTs) and quasi-randomized controlled trials (quasi-RCTs).
SEARCH METHODS
We searched databases including The Cochrane Central Register of Controlled Trials (The Cochrane Library 2014, Issue 4), MEDLINE (PubMed, January 1966 to April 2014), EMBASE (January 1978 to April 2014) and ISI Web of Knowledge (January 1966 to April 2014), online trials registries and other sources. We also screened the reference lists of related literature and eligible studies, and presentations from major HIV/AIDS (human immunodeficiency virus/acquired immunodeficiency syndrome) conferences.
SELECTION CRITERIA
We included RCTs and quasi-RCTs comparing PRO 140 with placebo or other antiretroviral drugs, or different doses of PRO 140 for individuals infected with HIV.
DATA COLLECTION AND ANALYSIS
Two reviewers (L Li and JH Tian) independently screened all retrieved citations and selected eligible studies. Two authors (P Zhang and WQ Jia) independently extracted data. Any disagreements when selecting studies and extracting data were adjudicated by the review mentor (KH Yang). We used Review Manager (RevMan) software for statistical analysis based on an intention-to-treat analysis. We examined heterogeneity using the Chi(2) statistic. We regarded I(2) estimates greater than 50% as moderate or high levels of heterogeneity. According to the level of heterogeneity, we used either a fixed or random-effects model.If significant heterogeneity existed and the reasons could not be found, we reported the results qualitatively.
MAIN RESULTS
We included three trials comparing PRO 140 with placebo in adult patients with HIV infection. Our review indicates that PRO 140 may offer significant dose-dependent HIV-1 RNA suppression with tolerable side effects. PRO 140 2 mg/kg, 5 mg/kg, 10 mg/kg, 162 mg weekly, 324 mg biweekly, and 324 mg weekly showed statistically significant differences in the changes of HIV-1 RNA levels. HIV-1 RNA levels were reduced by intravenous (IV) infusion of PRO 140 2 mg/kg or 5 mg/kg on day 10, 5 mg/kg or 10 mg/kg on day 12, 162 mg weekly, 324 mg biweekly, or 324 mg weekly on day 22. PRO 140 2 mg/kg, 5 mg/kg, 10 mg/kg, 162 mg weekly, 324 mg biweekly, and 324 mg weekly demonstrated greater antiviral response. PRO 140 324 mg weekly, 5 mg/kg, and 10 mg/kg showed more patients with ≦ 400 copies/mL HIV-1 RNA. Only PRO 140 5 mg/kg showed greater change in CD4(+) cell count on day eight. Headache, lymphadenopathy, diarrhoea, fatigue, hypertension, nasal congestion and pruritus were reported to be the most frequent adverse events.
AUTHORS' CONCLUSIONS
Limited evidence from three small trials suggests that PRO 140 might demonstrate potent, short-term, dose-dependent, highly significant antiviral activity. However, as the evidence is insufficient, recommendations cannot yet be made. Larger, longer-term, double-blind RCTs are required to provide conclusive evidence.
Topics: Adult; Anti-HIV Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; CCR5 Receptor Antagonists; Drug Administration Schedule; HIV Antibodies; HIV Infections; HIV-1; Humans; RNA, Viral; Randomized Controlled Trials as Topic
PubMed: 25063928
DOI: 10.1002/14651858.CD008439.pub3 -
Jornal de Pediatria 2019Human immunodeficiency virus infection can result in the early impairment of anthropometric indicators in children and adolescents. However, combined antiretroviral...
OBJECTIVES
Human immunodeficiency virus infection can result in the early impairment of anthropometric indicators in children and adolescents. However, combined antiretroviral therapy has improved, in addition to the immune response and viral infection, the weight and height development in infected individuals. Therefore, the objective was to evaluate the effect of combined antiretroviral on the growth development of human immunodeficiency virus infected children and adolescents.
SOURCE OF DATA
A systematic review was performed. In the study, the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) strategy was used as the eligibility criterion. The MEDLINE-PubMed and LILACS databases were searched using these descriptors: HIV, children, growth, antiretroviral therapy. The objective was defined by the population, intervention, comparison/control, and outcome (PICO) technique. Inclusion and exclusion criteria were applied for study selection.
SYNTHESIS OF DATA
Of the 549 studies indexed in MEDLINE-PubMed and LILACS, 73 were read in full, and 44 were included in the review (33 showed a positive impact of combined antiretroviral therapy on weight/height development, ten on weight gain, and one on height gain in children and adolescents infected with human immunodeficiency virus). However, the increase in growth was not enough to normalize the height of infected children when compared to children of the same age and gender without human immunodeficiency virus infection.
CONCLUSIONS
Combined antiretroviral therapy, which is known to play a role in the improvement of viral and immunological markers, may influence in the weight and height development in children infected with human immunodeficiency virus. The earlier the infection diagnosis and, concomitantly, of malnutrition and the start of combined antiretroviral therapy, the lower the growth impairment when compared to healthy children.
Topics: Adolescent; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Body Height; Body Weight; Child; Child Development; Child, Preschool; Growth; HIV Infections; Humans; Infant; Infant, Newborn; Young Adult
PubMed: 29660296
DOI: 10.1016/j.jped.2018.02.006 -
Experimental and Therapeutic Medicine Nov 2019Sustained virological response (SVR) in hepatitis C virus (HCV) patients treated with pegylated interferon α-2a and ribavirin is associated with reduced insulin...
Sustained virological response (SVR) in hepatitis C virus (HCV) patients treated with pegylated interferon α-2a and ribavirin is associated with reduced insulin resistance (IR), measured as a reduction of homeostasis model assessment (HOMA) scores after 24 weeks of therapy, and reduced fasting serum insulin and serum glucose levels. The present meta-analysis aimed to evaluate the effect of HCV treatment response on IR in HCV patients who achieved SVR and those who did not (non-SVR) after receiving interferon (IFN)-based therapy. The PubMed, Cochrane and Embase databases were searched using combinations of the following search terms: 'HCV', 'hepatitis C', 'interferon', 'antiviral', 'treatment response' and 'insulin resistance'. The incidence of IR, HOMA-IR and HOMA-β, as well as fasting glucose and fasting insulin levels, were summarized in terms of basal values and values after the end of treatment for each study. A total of 8 studies were included in the final analysis. There was no significant difference in the reduction in IR between the SVR and non-SVR groups (odds ratio, 0.995; 95% CI=0.613-1.616; P=0.984). However, the SVR group had a significantly higher mean reduction in HOMA-IR (difference in means=-0.485; 95%CI=-0.713 to -0.256; P<0.001) and HOMA-β (difference in means=-15.448; 95%CI=-23.326 to -7.570; P<0.001) compared to the non-SVR group. In conclusion, HCV patients who achieved SVR after IFN-based therapy exhibited improvement in HOMA-IR and HOMA-β. The present results suggest that clinical management of IR and serum glucose levels may be an important way to impact the therapeutic response in HCV patients.
PubMed: 31602234
DOI: 10.3892/etm.2019.7995 -
Health Technology Assessment... Oct 2014Optimal therapy for children with chronic hepatitis C is unclear. Two treatment regimens are currently licensed in children. (Review)
Review
The clinical effectiveness and cost-effectiveness of peginterferon alfa and ribavirin for the treatment of chronic hepatitis C in children and young people: a systematic review and economic evaluation.
BACKGROUND
Optimal therapy for children with chronic hepatitis C is unclear. Two treatment regimens are currently licensed in children.
OBJECTIVES
To assess the clinical effectiveness and cost-effectiveness of peginterferon alfa-2a (Pegasys®, Roche) and peginterferon alfa-2b [ViraferonPeg®, Merck Sharp & Dohme (MSD)] in combination with ribavirin (RBV), within their licensed indications, for the treatment of chronic hepatitis C virus (HCV) in children and young people aged 3-17 years.
DATA SOURCES
Twelve electronic bibliographic databases, including The Cochrane Library, MEDLINE and EMBASE, were searched from inception to November 2012. Bibliographies of retrieved papers, key hepatitis C websites and symposia and manufacturers' submissions to the National Institute for Health and Care Excellence were also searched, and clinical experts were contacted.
REVIEW METHODS
Systematic reviews of clinical effectiveness and cost-effectiveness were conducted, including studies of health-related quality of life (HRQoL), following standard guidelines to ensure methodological rigour. Clinical effectiveness studies were included if they were in children and young people aged 3-17 years with chronic compensated HCV of any severity, including those with human immunodeficiency virus co-infection and those who were treatment naive or had been previously treated. Eligible interventions were peginterferon alfa-2a or peginterferon alfa-2b, each in combination with RBV, compared against best supportive care (BSC) or against each other, and study designs were randomised controlled trials (RCTs) or non-RCTs, or uncontrolled cohort studies. Outcomes included sustained virological response (SVR) and adverse events. Previously published Markov state-transition economic models of chronic HCV in adults were adapted to estimate the cost-effectiveness of peginterferon alfa-2a and -2b (in combination with RBV), compared with BSC and with one another in children. The model extrapolated the impact of SVR on life expectancy, quality-adjusted life expectancy and lifetime costs. Uncertainty was explored through probabilistic and deterministic sensitivity analyses.
RESULTS
Seven studies [two peginterferon alfa-2a and RBV (Copegus®, Roche), and five peginterferon alfa-2b and RBV (Rebetol®, MSD)] were included in the review of clinical effectiveness. Six were single-arm cohort studies and one was a RCT for which only those data for a single arm met the inclusion criteria. Overall, the studies were relatively small and of generally poor quality. SVR rates ranged from 53% to 66% (peginterferon alfa-2a) and 29% to 75% (peginterferon alfa-2b) (49% to 65% if excluding two studies with very small sample sizes). Rates of non-response and relapse were variable and adverse events were generally mild. No studies of cost-effectiveness or HRQoL in children and young people met the inclusion criteria. HRQoL, utilities and costs of treatment were therefore taken from studies of adults with chronic HCV. From this model, peginterferon alfa (-2a or -2b) in combination with RBV was more effective and had lower lifetime costs than BSC. Peginterferon alfa-2a had slightly lower lifetime costs and higher quality-adjusted life-years than peginterferon alfa-2b; therefore, peginterferon alfa-2b was dominated by peginterferon alfa-2a. Results were robust to changes in the sensitivity analyses.
LIMITATIONS
There were few good quality studies and parameter data had to be taken from adult studies, which is a limitation of the work.
CONCLUSIONS
Treatment of children and young people with peginterferon (alfa-2a or -2b) and RBV may be an effective therapy. Results from the independent Markov model suggest that peginterferon (alfa-2a or -2b) in combination with RBV is cost-effective compared with BSC. However, the available evidence is of poor quality. Future research into the impact of these treatments on growth and quality of life in children and young people is recommended.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42012002743.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Adolescent; Antiviral Agents; Biomarkers; Child; Child Development; Child, Preschool; Clinical Trials as Topic; Cost-Benefit Analysis; Drug Therapy, Combination; Female; Genotype; Hepatitis C, Chronic; Humans; Interferon alpha-2; Interferon-alpha; Liver; Male; Markov Chains; Models, Econometric; Polyethylene Glycols; Quality of Life; Quality-Adjusted Life Years; RNA, Viral; Recombinant Proteins; Ribavirin; Viral Load
PubMed: 25350588
DOI: 10.3310/hta18650 -
Clinical Therapeutics Jun 2022Heavily treatment-experienced (HTE) people with multidrug-resistant HIV-1 have limited treatment options. Treatment with the first-in-class attachment inhibitor...
PURPOSE
Heavily treatment-experienced (HTE) people with multidrug-resistant HIV-1 have limited treatment options. Treatment with the first-in-class attachment inhibitor fostemsavir in addition to optimized background therapy (OBT) resulted in sustained virologic and immunologic responses in HTE participants throughout 96 weeks in the BRIGHTE trial. In the absence of long-term direct comparative evidence between fostemsavir-based and other antiretroviral regimens, this analysis indirectly compares efficacy and safety across relevant available trials, adjusting for demographic and baseline characteristics.
METHODS
A systematic literature review was conducted to identify trials with designs and populations comparable to BRIGHTE. Using matching-adjusted indirect comparison analyses, individual participant data from BRIGHTE were reweighted to create balanced populations across trials, and efficacy and safety outcomes were compared.
FINDINGS
Three comparator trials were identified, 2 of which reflected an optimized therapy without fostemsavir (OBT alone): TMB-301 (ibalizumab and OBT), BENCHMRK-1/-2 (OBT alone), and VIKING-3 (OBT alone). Compared with ibalizumab and OBT (N = 40), fostemsavir and OBT (unadjusted, N = 347; adjusted, N = 236) were associated with numerically higher nonsignificant odds of virologic suppression (odds ratio [OR] = 1.44; 95% CI, 0.74-2.80; P = 0.284) and a similar increase in CD4 cell count of approximately 65 cells/mm from baseline through week 24 (mean difference = 7.05 cells/mm; 95% CI, -60.88 to 74.98 cells/mm; P = 0.834). Compared with OBT from BENCHMRK-1/-2 (N = 237), fostemsavir and OBT (adjusted, N = 126) were associated with significantly higher odds of virologic suppression (OR = 3.26; 95% CI, 2.08-5.11; P < 0.001) and increased CD4 cell count (135.78 cells/mm; 95% CI, 91.93-179.63 cells/mm; P < 0.001) at week 96. Compared with OBT from VIKING-3 (N = 183), fostemsavir and OBT (adjusted, N = 78) were associated with numerically higher odds of virologic suppression (OR = 1.34; 95% CI, 0.78-2.30; P = 0.297) and a modest CD4 cell count increase (26.86 cells/mm; 95% CI, -10.79 to 64.52; P = 0.162) through week 48; however, differences were not significant. All-cause discontinuations and safety comparisons varied across studies.
IMPLICATIONS
Although matching-adjusted indirect comparison analyses have limitations, these results support the use of fostemsavir and OBT as an important treatment option in HTE people with multidrug-resistant HIV-1.
Topics: Anti-HIV Agents; HIV Infections; HIV-1; Humans; Organophosphates; Piperazines; Viral Load
PubMed: 35610081
DOI: 10.1016/j.clinthera.2022.04.007 -
BMC Infectious Diseases Jan 2015The goal of chronic hepatitis C treatment is to remove the virus to avoid progression of HCV-related disease. Sustained virologic response (SVR) is the most widely used... (Review)
Review
BACKGROUND
The goal of chronic hepatitis C treatment is to remove the virus to avoid progression of HCV-related disease. Sustained virologic response (SVR) is the most widely used efficacy endpoint in clinical studies of hepatitis C, and represents the eradication of HCV from the body. The aim of the current review was to examine the long-term clinical, economic and quality of life benefits associated with achieving SVR.
METHODS
A systematic literature review was performed using the PubMed, EMBASE and Cochrane library databases to identify articles examining the clinical, economic and quality of life benefits associated with SVR, published in English language from 2002-2013. For inclusion studies were required to enroll ≥100 patients and to report clinical endpoints including hepatocellular carcinoma, overall- or liver-related mortality, or progression of disease/complications (e.g. portal hypertension, esophageal varices). Review of economic studies on cost/cost-effectiveness of achieving SVR were focused on studies assessing boceprevir/telaprevir plus pegIFN and ribavirin as this represents the current standard of care in several jurisdictions worldwide. Quality of life evidence was required to use validated quality of life instruments and provide a quantitative analysis of the impact of SVR versus no treatment or treatment failure.
RESULTS
SVR is durable with late relapse rates over 4-5 year periods being in the range of 1-2%. Patients who achieve SVR frequently demonstrate some regression of fibrosis/cirrhosis and have a substantially reduced risk for hepatocellular carcinoma (relative risk [RR] 0.1-0.25), liver-related mortality (RR 0.03-0.2) and overall mortality (RR 0.1-0.3) in comparison with no treatment or treatment failure. In the 5 years post-treatment, medical costs for patients achieving SVR are 13-fold lower than patients not achieving SVR. Patients who achieve SVR also have health state utility values that are 0.05 to 0.31 higher than non-responders to treatment.
CONCLUSIONS
SVR represents the fundamental goal of antiviral treatment for patients infected with chronic HCV, so as to reduce risk of liver disease progression. Achievement of SVR has implications beyond those of clearing viral infection; it is associated with improved long-term clinical outcomes, economic benefits and improved health-related quality of life.
Topics: Antiviral Agents; Cost-Benefit Analysis; Global Health; Health Care Costs; Hepatitis C, Chronic; Humans; Quality of Life
PubMed: 25596623
DOI: 10.1186/s12879-015-0748-8 -
Viruses Dec 2022Defective interfering particles (DIPs) are particles containing defective viral genomes (DVGs) generated during viral replication. DIPs have been found in various RNA... (Review)
Review
Defective interfering particles (DIPs) are particles containing defective viral genomes (DVGs) generated during viral replication. DIPs have been found in various RNA viruses, especially in influenza viruses. Evidence indicates that DIPs interfere with the replication and encapsulation of wild-type viruses, namely standard viruses (STVs) that contain full-length viral genomes. DIPs may also activate the innate immune response by stimulating interferon synthesis. In this review, the underlying generation mechanisms and characteristics of influenza virus DIPs are summarized. We also discuss the potential impact of DIPs on the immunogenicity of live attenuated influenza vaccines (LAIVs) and development of influenza vaccines based on NS1 gene-defective DIPs. Finally, we review the antiviral strategies based on influenza virus DIPs that have been used against both influenza virus and SARS-CoV-2. This review provides systematic insights into the theory and application of influenza virus DIPs.
Topics: Humans; Antiviral Agents; Influenza Vaccines; Defective Interfering Viruses; Defective Viruses; COVID-19; SARS-CoV-2; Orthomyxoviridae; Virus Replication
PubMed: 36560777
DOI: 10.3390/v14122773