-
Immunity, Inflammation and Disease Apr 2024This systematic review and meta-analysis aimed to compare the effectiveness and safety of molnupiravir and sotrovimab in the treatment of patients with coronavirus... (Meta-Analysis)
Meta-Analysis Comparative Study Review
BACKGROUND AND AIM
This systematic review and meta-analysis aimed to compare the effectiveness and safety of molnupiravir and sotrovimab in the treatment of patients with coronavirus disease 2019 (COVID-19).
METHODS
Cochrane Library, Web of Science, PubMed, medRxiv, and Google Scholar were systematically searched to identify relevant evidence up to December 2023. The risk of bias was assessed using the risk of bias in nonrandomized studies of interventions tool. Data were analyzed using Comprehensive Meta-Analysis (CMA).
RESULTS
Our search identified and included 13 studies involving 16166 patients. The meta-analysis revealed a significant difference between the molnupiravir and sotrovimab groups in terms of the mortality rate (odds ratio [OR] = 2.07, 95% confidence interval [CI]: 1.16, 3.70). However, no significant difference was observed between the two groups in terms of hospitalization rate (OR = 0.71, 95% CI: 0.47, 1.06), death or hospitalization rate (OR = 1.51, 95% CI: 0.81, 2.83), and intensive care unit admission (OR = 0.59, 95% CI: 0.07, 4.84). In terms of safety, molnupiravir was associated with a higher incidence of adverse events (OR = 1.67, 95% CI: 1.21, 2.30).
CONCLUSION
The current findings indicate that sotrovimab may be more effective than molnupiravir in reducing the mortality rate in COVID-19 patients. However, no statistical difference was observed between the two treatments for other effectiveness outcomes. The certainty of evidence for these findings was rated as low or moderate. Further research is required to provide a better comparison of these interventions in treating COVID-19 patients.
Topics: Humans; COVID-19 Drug Treatment; Hydroxylamines; Cytidine; Antiviral Agents; SARS-CoV-2; Antibodies, Monoclonal, Humanized; COVID-19; Treatment Outcome; Hospitalization; Antibodies, Neutralizing
PubMed: 38652021
DOI: 10.1002/iid3.1262 -
PloS One 2024Pretreatment drug resistance (PDR) could occur in antiretroviral treatment (ART) naïve individuals, those previously exposed to ART, or individuals re-initiating ARV... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Pretreatment drug resistance (PDR) could occur in antiretroviral treatment (ART) naïve individuals, those previously exposed to ART, or individuals re-initiating ARV after a long period of interruption. Few studies have shown its association with virological outcomes, although inconsistent. The objective of this review was to provide a synthesis of the association between PDR and virological outcomes (virological failure or suppression).
METHODS
This report is presented following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The method was subdivided into three main phases: record identification, screening, and report inclusion. Record identification consisted of an initial search with search term "HIV pretreatment drug resistance". Another search was done using terms "Pretreatment drug resistance OR pre-treatment drug resistance OR Pretreatment drug resist* OR pre-treatment drug resist* OR pretreatment antiretroviral resistance OR pretreatment medic* OR pretreatment medic* resist*" and a list of all the countries in sub-Saharan Africa. After the electronic search, studies were screened from full list based on their title and abstract and then full articles retrieved and studies were assessed based on set criteria. Inclusion criteria involved observational studies that report the association between PDR and virological failure. Data from trials that reported the association were also included. Published articles like modelling studies and reviews, and studies with data that had been previously included in the review were excluded. The Mantel Haenszel method with odds ratios was used for synthesis (meta-analyses) with the weights of each study which depends on the number of events and totals.
RESULTS
A total of 733 records(studies) were obtained from all database search of which 74 reported on PDR, virological outcomes in sub-Saharan Africa (SSA). Out of the 74 articles, 11 were excluded and 26 did not explicitly report data needed, and 5 did not meet the inclusion criteria. Of the remaining 32 studies, 19 studies that had complete data on the number of participants with PDR and no PDR according to virological failure (VF) were included in the metanalyses. The pooled results from eleven (13) of these studies showed those with PDR had higher odds of virological failure compared to those without PDR OR 3.64[95% CI 2.93, 4.52]. The result was similar when stratified in adults and in children. In six (6) studies that had Virological suppression (VS) as outcome, there was a reduction in the odds of VS in those with PDR compared to those without PDR, OR 0.42 (95% CI 0.30, 0.58).
CONCLUSION
In conclusion, this systematic review indicates that PDR increases the risk of virological failure in sub-Saharan Africa. The risk could be reduced by PDR monitoring for NNRTIs and INSTIs.
Topics: Adult; Child; Humans; Anti-HIV Agents; HIV Infections; HIV-1; Anti-Retroviral Agents; Africa South of the Sahara; Drug Resistance, Viral; Viral Load
PubMed: 38626183
DOI: 10.1371/journal.pone.0300456 -
World Journal of Gastroenterology Mar 2024Direct-acting antiviral agents (DAAs) are highly effective treatment for chronic hepatitis C (CHC) with a significant rate of sustained virologic response (SVR). The... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Direct-acting antiviral agents (DAAs) are highly effective treatment for chronic hepatitis C (CHC) with a significant rate of sustained virologic response (SVR). The achievement of SVR is crucial to prevent additional liver damage and slow down fibrosis progression. The assessment of fibrosis degree can be performed with transient elastography, magnetic resonance elastography or shear-wave elastography (SWE). Liver elastography could function as a predictor for hepatocellular carcinoma (HCC) in CHC patients treated with DAAs.
AIM
To explore the predictive value of SWE for HCC development after complete clearance of hepatitis C virus (HCV).
METHODS
A comprehensive literature search of clinical studies was performed to identify the ability of SWE to predict HCC occurrence after HCV clearance. In accordance with the study protocol, a qualitative and quantitative analysis of the evidence was planned.
RESULTS
At baseline and after 12 wk of follow-up, a trend was shown towards greater liver stiffness (LS) in those who go on to develop HCC compared to those who do not [baseline LS standardized mean difference (SMD): 1.15, 95% confidence interval (95%CI): 020-2.50; LS SMD after 12 wk: 0.83, 95%CI: 0.33-1.98]. The absence of a statistically significant difference between the mean LS in those who developed HCC or not may be related to the inability to correct for confounding factors and the absence of raw source data. There was a statistically significant LS SMD at 24 wk of follow-up between patients who developed HCC not (0.64; 95%CI: 0.04-1.24).
CONCLUSION
SWE could be a promising tool for prediction of HCC occurrence in patients treated with DAAs. Further studies with larger cohorts and standardized timing of elastographic evaluation are needed to confirm these data.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Hepacivirus; Elasticity Imaging Techniques; Antiviral Agents; Hepatitis C, Chronic; Sustained Virologic Response; Fibrosis; Liver Cirrhosis; Hepatitis C
PubMed: 38596502
DOI: 10.3748/wjg.v30.i10.1450 -
Journal of Viral Hepatitis Jul 2024The impact of concurrent fatty liver (FL) on response to antiviral therapy in chronic hepatitis B (CHB) patients has not been well characterized. We aimed to... (Meta-Analysis)
Meta-Analysis
The impact of concurrent fatty liver (FL) on response to antiviral therapy in chronic hepatitis B (CHB) patients has not been well characterized. We aimed to systematically review and analyse antiviral treatment response in CHB patients with and without FL. We searched PubMed, Embase, Web of Science and the Cochrane Library databases from inception to 31 May 2023 for relevant studies. Biochemical response (BR), complete viral suppression (CVS) and hepatitis B e antigen (HBeAg) seroconversion in CHB patients with FL (CHB-FL) and without FL (non-FL CHB) were compared. In an initial pool of 2101 citations, a total of 10 studies involving 2108 patients were included. After 12 weeks of treatment, CHB-FL patients as compared with non-FL CHB patients had lower BR rate (48.37% [108/227] vs. 72.98% [126/174], p = .04) but similar trend for CVS (36.86% [80/227] vs. 68.81% [114/174], p = .05) and similar rates of HBeAg seroconversion (6.59% [7/103] vs. 7.40% [7/110], p = .89). However, at week 48, there were no statistically significant differences between CHB-FL and non-FL CHB patients in any of the outcomes, including BR (60.03% [213/471] vs. 69.37% [314/717], p = .67), CVS (65.63% [459/746] vs. 73.81% [743/1132], p = .27) and HBeAg seroconversion (10.01% [30/275] vs. 14.06% [65/453], p = .58) with similar findings for week 96. BR rate was lower in CHB-FL patients after 12 weeks of antiviral treatment. However, after a longer follow-up of either 48 or 96 weeks, no statistically significant differences were observed in BR, CVS or HBeAg seroconversion rates between CHB patients with and without FL.
Topics: Humans; Hepatitis B, Chronic; Antiviral Agents; Hepatitis B e Antigens; Treatment Outcome; Fatty Liver; Seroconversion; Hepatitis B virus; DNA, Viral
PubMed: 38590002
DOI: 10.1111/jvh.13942 -
The Lancet. Microbe May 2024Surrogates of antiviral efficacy are needed for COVID-19. We aimed to investigate the relationship between the virological effect of treatment and clinical efficacy as... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Surrogates of antiviral efficacy are needed for COVID-19. We aimed to investigate the relationship between the virological effect of treatment and clinical efficacy as measured by progression to severe disease in outpatients treated for mild-to-moderate COVID-19.
METHODS
In this systematic review and meta-analysis, we searched PubMed, Scopus, and medRxiv from database inception to Aug 16, 2023, for randomised placebo-controlled trials that tested virus-directed treatments (ie, any monoclonal antibodies, convalescent plasma, or antivirals) in non-hospitalised individuals with COVID-19. We only included studies that reported both clinical outcomes (ie, rate of disease progression to hospitalisation or death) and virological outcomes (ie, viral load within the first 7 days of treatment). We extracted summary data from eligible reports, with discrepancies resolved through discussion. We used an established meta-regression model with random effects to assess the association between clinical efficacy and virological treatment effect, and calculated I to quantify residual study heterogeneity.
FINDINGS
We identified 1718 unique studies, of which 22 (with a total of 16 684 participants) met the inclusion criteria, and were in primarily unvaccinated individuals. Risk of bias was assessed as low in 19 of 22 studies for clinical outcomes, whereas for virological outcomes, a high risk of bias was assessed in 11 studies, some risk in ten studies, and a low risk in one study. The unadjusted relative risk of disease progression for each extra log copies per mL reduction in viral load in treated compared with placebo groups was 0·12 (95% CI 0·04-0·34; p<0·0001) on day 3, 0·20 (0·08-0·50; p=0·0006) on day 5, and 0·53 (0·30-0·94; p=0·030) on day 7. The residual heterogeneity in our meta-regression was estimated as low (I=0% [0-53] on day 3, 0% [0-71] on day 5, and 0% [0-43] on day 7).
INTERPRETATION
Despite the aggregation of studies with differing designs, and evidence of risk of bias in some virological outcomes, this review provides evidence that treatment-induced acceleration of viral clearance within the first 5 days after treatment is a potential surrogate of clinical efficacy to prevent hospitalisation with COVID-19. This work supports the use of viral clearance as an early phase clinical trial endpoint of therapeutic efficacy.
FUNDING
Australian Government Department of Health, Medical Research Future Fund, and Australian National Health and Medical Research Council.
Topics: Humans; COVID-19; Antiviral Agents; Viral Load; SARS-CoV-2; Treatment Outcome; COVID-19 Drug Treatment; Outpatients; Immunization, Passive; Randomized Controlled Trials as Topic; COVID-19 Serotherapy; Disease Progression; Hospitalization
PubMed: 38583464
DOI: 10.1016/S2666-5247(23)00398-1 -
Expert Opinion on Drug Metabolism &... Apr 2024Since COVID-19 patients are often polytreated, monitoring drug-drug interaction (DDIs) is necessary. We evaluated whether drugs used after the second COVID-19 pandemic...
INTRODUCTION
Since COVID-19 patients are often polytreated, monitoring drug-drug interaction (DDIs) is necessary. We evaluated whether drugs used after the second COVID-19 pandemic wave were associated with DDI-related adverse events and the role of drug interaction checkers in identifying them.
METHODS
The study (PROSPERO-ID: CRD42024507634) included: 1) consulting the drug interaction checkers Drugs.com, Liverpool COVID-19 Interactions, LexiComp, Medscape, and Micromedex; 2) systematic review; 3) reviewed studies analysis; 4) evaluating drug interaction checkers potential to anticipate DDI-related adverse events.The systematic review was performed searching PubMed, Scopus, ScienceDirect, and Cochrane databases from 1 March 2022 to 11 November 2023. Observational studies, and clinical trials were included. Article without reporting direct association between DDIs and adverse events were excluded. The risk of bias was assessed by Newcastle-Ottawa scale.
RESULTS
The most frequent DDIs involved nirmatrelvir/ritonavir (N/R) and fluvoxamine. Fifteen studies, including 150 patients and 35 DDI-related outcomes, were analyzed. The most frequent DDIs involved tacrolimus with N/R, resulting in creatinine increase.Eighty percent of reported DDI-related adverse events would have been identified by all drug-interaction checkers, while the remaining 20% by at least 2 of them.
CONCLUSIONS
Drug interaction checkers are useful but show inconsistencies. Multiple sources are needed to tailor treatment in the context of COVID-19.
Topics: Humans; Antiviral Agents; COVID-19; COVID-19 Drug Treatment; Drug Interactions; Drug-Related Side Effects and Adverse Reactions
PubMed: 38568077
DOI: 10.1080/17425255.2024.2339397 -
The Journal of the Association of...Clinical trials of pre-exposure prophylaxis (PrEP) to prevent HIV infection have established its efficacy as upwards of 99%. Despite this, the effectiveness of this...
Clinical trials of pre-exposure prophylaxis (PrEP) to prevent HIV infection have established its efficacy as upwards of 99%. Despite this, the effectiveness of this medication has been shown to be diminished by individual factors, such as medication adherence. We completed a systematic review to identify and describe interventions to improve oral PrEP adherence. Overall, 16 articles were located. Two of the articles reported on results from the same trial and were collapsed for analysis, bringing the total to 15 studies. Twelve unique PrEP adherence interventions were tested, with the most common intervention being the use of mobile phone technology, which was used in 7 (46%) of the studies. Ten (67%) studies found that medication adherence improved when participants received an intervention to support adherence. Adherence intervention strategies effectively improved PrEP adherence. Further research into PrEP adherence interventions is warranted, particularly among diverse groups.
Topics: Humans; HIV Infections; Pre-Exposure Prophylaxis; Medication Adherence; Anti-HIV Agents; Administration, Oral; Cell Phone; Male
PubMed: 38564213
DOI: 10.1097/JNC.0000000000000460 -
AIDS and Behavior Jul 2024Implementation of pre-exposure prophylaxis (PrEP) to prevent HIV transmission is suboptimal in the United States. To date, the literature has focused on identifying...
Implementation of pre-exposure prophylaxis (PrEP) to prevent HIV transmission is suboptimal in the United States. To date, the literature has focused on identifying determinants of PrEP use, with a lesser focus on developing and testing change methods to improve PrEP implementation. Moreover, the change methods available for improving the uptake and sustained use of PrEP have not been systematically categorized. To summarize the state of the literature, we conducted a systematic review of the implementation strategies used to improve PrEP implementation among delivery systems and providers, as well as the adjunctive interventions used to improve the uptake and persistent adherence to PrEP among patients. Between November 2020 and January 2021, we searched Ovid MEDLINE, PsycINFO, and Web of Science for peer reviewed articles. We identified 44 change methods (18 implementation strategies and 26 adjunctive interventions) across a variety of clinical and community-based service settings. We coded implementation strategies and adjunctive interventions in accordance with established taxonomies and reporting guidelines. Most studies focused on improving patient adherence to PrEP and most conducted pilot trials. Just over one-third of included studies demonstrated a positive effect on outcomes. In order to end the human immunodeficiency virus (HIV) epidemic in the U.S., future, large scale HIV prevention research is needed that develops and evaluates implementation strategies and adjunctive interventions for target populations disproportionately affected by HIV.
Topics: Humans; Pre-Exposure Prophylaxis; HIV Infections; United States; Anti-HIV Agents; Medication Adherence
PubMed: 38564136
DOI: 10.1007/s10461-024-04331-0 -
Diseases (Basel, Switzerland) Feb 2024Plasma collected from people recovered from COVID-19 (COVID-19 convalescent plasma, CCP) was the first antibody-based therapy employed to fight the pandemic. CCP was,... (Review)
Review
Safety and Efficacy of Convalescent Plasma Combined with Other Pharmaceutical Agents for Treatment of COVID-19 in Hospitalized Patients: A Systematic Review and Meta-Analysis.
Plasma collected from people recovered from COVID-19 (COVID-19 convalescent plasma, CCP) was the first antibody-based therapy employed to fight the pandemic. CCP was, however, often employed in combination with other drugs, such as the antiviral remdesivir and glucocorticoids. The possible effect of such interaction has never been investigated systematically. To assess the safety and efficacy of CCP combined with other agents for treatment of patients hospitalized for COVID-19, a systematic literature search using appropriate Medical Subject Heading (MeSH) terms was performed through PubMed, EMBASE, Cochrane central, medRxiv and bioRxiv. The main outcomes considered were mortality and safety of CCP combined with other treatments versus CCP alone. This review was carried out in accordance with Cochrane methodology including risk of bias assessment and grading of the quality of evidence. Measure of treatment effect was the risk ratio (RR) together with 95% confidence intervals (CIs). A total of 11 studies (8 randomized controlled trials [RCTs] and 3 observational) were included in the systematic review, 4 studies with CCP combined with remdesivir and 6 studies with CCP combined with corticosteroids, all involving hospitalized patients. One RCT reported information on both remdesivir and steroids use with CCP. The use of CCP combined with remdesivir was associated with a significantly reduced risk of death (RR 0.74; 95% CI 0.56-0.97; = 0.03; moderate certainty of evidence), while the use of steroids with CCP did not modify the mortality risk (RR 0.72; 95% CI 0.34-1.51; = 0.38; very low certainty of evidence). Not enough safety data were retrieved form the systematic literature analysis. The current evidence from the literature suggests a potential beneficial effect on mortality of combined CCP plus remdesivir compared to CCP alone in hospitalized COVID-19 patients. No significant clinical interaction was found between CCP and steroids.
PubMed: 38534965
DOI: 10.3390/diseases12030041 -
Drug and Therapeutics Bulletin Mar 2024Hanula R, Bortolussi-Courval É, Mendel A, et al. Evaluation of oseltamivir used to prevent hospitalization in outpatients with influenza: a systematic review and... (Meta-Analysis)
Meta-Analysis
Hanula R, Bortolussi-Courval É, Mendel A, et al. Evaluation of oseltamivir used to prevent hospitalization in outpatients with influenza: a systematic review and meta-analysis. JAMA Internal Medicine 2024;184:18-27.
Topics: Humans; Oseltamivir; Influenza, Human; Antiviral Agents; Treatment Outcome; Hospitalization
PubMed: 38527768
DOI: 10.1136/dtb.2024.000016