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BMC Infectious Diseases Oct 2023To compare the effectiveness of seven major interventions [Bulevirtide (BLV), Interferon (IFN), Nucleoside analogs (NAs), BLV + IFN, BLV + NAs, IFN + NAs,... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To compare the effectiveness of seven major interventions [Bulevirtide (BLV), Interferon (IFN), Nucleoside analogs (NAs), BLV + IFN, BLV + NAs, IFN + NAs, and Placebo] to treat chronic hepatitis D.
METHODS
We followed PRISMA-NMA guidelines, searched databases (Cochrane Library, PubMed, EMBASE, and Web Of Science) for eligible randomized controlled trials (RCTs), and applied STATA17.0 software to execute the meta-analysis.
RESULTS
We included 14 randomized controlled trials (814 patients) comparing seven different interventions. The results of the network meta-analysis showed that: ① Sustained virological response (after 24 weeks of follow-up): Four intervention groups (BLV + IFN, IFN alone, IFN + NAs, and NAs alone) were effective (relative risk (RR) = 13.30, 95% confidence interval (Cl) [1.68,105.32], RR = 12.13, 95% Cl [1.46,101.04], RR = 5.05, 95% Cl [1.68,15.19], RR = 5.03, 95% Cl [1.66,15.20]), with no statistically significant differences between the four groups. The top three in probability rankings were: BLV + NAs, BLV + IFN, and BLV alone (surface under the cumulative ranking curve (SUCRA) = 86.8%, 80.3%, and 48.4%; ② Sustained biochemical response (after 24 weeks of follow-up): BLV + IFN and IFN were superior to BLV (RR = 14.71, 95% Cl [1.14,189.07], RR = 16.67, 95% Cl [1.39,199.52]). The top three were BLV alone, BLV + NAs, and BLV + IFN (SUCRA = 86.9%,81.2%, and 64.3%). ③ Histological response: NAs were superior to BLV (RR = 2.08, 95% Cl [1.10,3.93]), whereas the difference between other treatment regimens was not statistically significant, and the top three in the probability ranking were BLV alone, BLV + NAs, and BLV + IFN (SUCRA = 75.6%, 75.6%, and 61.8%).
CONCLUSIONS
IFN, IFN + BLV, and IFN + NAs were effective in clearing HDV RNA and normalizing alanine aminotransferase levels; however, IFN and IFN + NAs had a high rate of viral relapse at 24 weeks post-treatment follow-up. There was no additional benefit of adding NAs to IFN therapy for chronic hepatitis D; however, the combination of IFN + BLV significantly improved short-term HDV RNA clearance, which showed strong synergistic effects. The seven regimens included in the study did not contribute significantly to liver histological improvement. Therefore, the IFN + BLV combination has the most potential as a treatment option to improve the long-term prognosis or even cure chronic hepatitis D.
TRIAL REGISTRATION
This systematic evaluation and meta-analysis was registered with PROSPERO under the registration number: CRD42022314544.).
Topics: Humans; Network Meta-Analysis; Hepatitis D, Chronic; Randomized Controlled Trials as Topic; Interferons; RNA; Antiviral Agents
PubMed: 37880598
DOI: 10.1186/s12879-023-08718-7 -
American Journal of Kidney Diseases :... Oct 2023Direct-acting antiviral (DAA) treatment of hepatitis C virus (HCV) infection in patients with chronic kidney disease (CKD) has made transplantation of kidneys from... (Meta-Analysis)
Meta-Analysis
Kidney Transplantation From Hepatitis C Virus-Infected Donors to Uninfected Recipients: A Systematic Review for the KDIGO 2022 Hepatitis C Clinical Practice Guideline Update.
RATIONALE & OBJECTIVE
Direct-acting antiviral (DAA) treatment of hepatitis C virus (HCV) infection in patients with chronic kidney disease (CKD) has made transplantation of kidneys from HCV-infected donors to uninfected recipients (D+/R-) feasible. To facilitate an update to the 2018 KDIGO guideline for patients with CKD and HCV, we conducted a systematic review of HCV D+/R-kidney transplantation coupled with DAA treatment.
STUDY DESIGN
Systematic review and meta-analysis.
SETTING & STUDY POPULATIONS
We included studies of HCV D+/R-kidney transplantations that used any DAA protocol.
SELECTION CRITERIA FOR STUDIES
Based on a search of PubMed, Embase, Cochrane, CINAHL, and ClinicalTrials.gov through February 1, 2022, conferences from 2019 to 2021, and the 2018 KDIGO HCV guideline we identified single-group (D+/R-) or comparative studies of D+/R-versus D-/R-kidney transplantation.
DATA EXTRACTION
Conducted in SRDR-Plus with review by a second researcher.
ANALYTICAL APPROACH
Maximum likelihood meta-analyses; the certainty of evidence was assessed per GRADE (Grading of Recommendations Assessment, Development and Evaluation).
RESULTS
We identified 16 studies (N=557). A sustained viral response at 12 weeks after treatment (SVR12) was observed in 97.7% (95% CI, 96.3%-98.8%). Ultrashort duration treatment (≤8 days) resulted in viremia requiring standard-course DAA treatment in some patients, all of whom achieved SVR12 after 1 or rarely 2 DAA courses. Serious adverse events from DAA treatment were rare after D+/R-transplantation (0.4% [95% CI, 0.1%-2.8%]). At≥1 year after D+/R-transplantation, recipient death occurred in 2.1% (95% CI, 0.9-3.7) and allograft survival was 97.6% (95% CI, 95.7%-98.9%). Estimated glomerular filtration rate 1 year after transplantation ranged from 46 to 74mL/min/1.73m.
LIMITATIONS
Analyses were generally based on low-certainty evidence. Uncertainty exists about the long-term safety and efficacy of D+/R-transplantation. Few studies investigated ultrashort treatment courses.
CONCLUSIONS
Kidney transplantation from HCV-infected donors to uninfected recipients followed by DAA treatment appears to be safe and associated with excellent 1-year clinical outcomes.
PLAIN-LANGUAGE SUMMARY
Due to the high efficacy of direct-acting antivirals (DAA), the use of kidneys from HCV-infected deceased donors may increase rates of kidney transplantation. We conducted a systematic review for the 2022 KDIGO Clinical Practice Guideline on Hepatitis C to evaluate the safety and efficacy of kidney transplantation from HCV-infected donors to uninfected recipients (D+/R-) followed by DAA therapy. Sixteen studies comprising 557 patients revealed high rates of sustained viral response, low rates of adverse events, and excellent patient and allograft survival 1 year after transplantation. Kidney transplantation from HCV-infected deceased donors to uninfected recipients treated with DAA appears safe and effective. Future studies should investigate shorter treatment durations, monitor safety, and obtain longer-term efficacy data.
Topics: Humans; Antiviral Agents; Hepacivirus; Kidney Transplantation; Hepatitis C, Chronic; Hepatitis C; Renal Insufficiency, Chronic; Tissue Donors
PubMed: 37061019
DOI: 10.1053/j.ajkd.2022.12.019 -
American Journal of TherapeuticsNirmatrelvir/ritonavir (NMV/r) is an oral antiviral drug used to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in patients aged 12 years or older at high...
BACKGROUND
Nirmatrelvir/ritonavir (NMV/r) is an oral antiviral drug used to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in patients aged 12 years or older at high risk of progression to severe disease (eg, hospitalization and death). Despite being the preferred option for outpatient treatment in the majority of countries worldwide, NMV/r is currently underutilized in real-world clinical practice.
AREAS OF UNCERTAINTY
As numerous real-world studies have described patient outcomes following treatment with NMV/r, this systematic literature review provides a comprehensive summary of evidence on NMV/r effectiveness against hospitalization and mortality further organized by clinically meaningful categories, such as acute versus longer-term follow-up, age, underlying health conditions, and vaccination status, to help inform health care decision making.
DATA SOURCES
We searched Embase and PubMed (December 22, 2021-March 31, 2023) and congress abstracts (December 1, 2021-December 31, 2022) for reports describing NMV/r effectiveness.
THERAPEUTIC ADVANCES
In total, 18 real-world studies met final selection criteria. The evidence showed that NMV/r significantly reduced postinfection risk of all-cause and COVID-19-related hospitalization and mortality in both acute (≤30 days) (21%-92%) and longer-term (>30 days) (1%-61%) follow-up. The reduction in postinfection risk was higher when treatment was received within 5 days of symptom onset. Real-world effectiveness of NMV/r treatment was observed regardless of age, underlying high-risk conditions, and vaccination status.
CONCLUSION
The systematic literature review findings demonstrated the effectiveness of NMV/r against hospitalization and mortality during the Omicron period among individuals at high risk of progression to severe COVID-19 disease.
Topics: Humans; Antiviral Agents; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Hospitalization; Ritonavir; SARS-CoV-2; Treatment Outcome
PubMed: 38691664
DOI: 10.1097/MJT.0000000000001744 -
BMJ Open Apr 2024To evaluate oral pre-exposure prophylaxis (PrEP) uptake, retention and adherence among female sex workers (FSWs) receiving care through community and facility delivery... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate oral pre-exposure prophylaxis (PrEP) uptake, retention and adherence among female sex workers (FSWs) receiving care through community and facility delivery models in sub-Saharan Africa (SSA).
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
We searched online databases (PubMed, MEDLINE, SCOPUS, EMBASE, Google Scholar, Cochrane Database of Systematic Reviews and Web of Science) between January 2012 and 3 April 2022.
ELIGIBILITY CRITERIA FOR STUDIES
Randomised controlled trials, cohort studies, cross-sectional studies and quasi-experimental studies with PrEP uptake, adherence and retention outcomes among FSWs in SSA.
DATA EXTRACTION AND SYNTHESIS
Seven coders extracted data. The framework of the Cochrane Consumers and Communication Review Group guided data synthesis. The Risk of Bias In Non-Randomized Studies of Interventions tool was used to evaluate the risk of bias. Meta-analysis was conducted using a random-effects model. A narrative synthesis was performed to analyse the primary outcomes of PrEP uptake, adherence and retention.
RESULTS
Of 8538 records evaluated, 23 studies with 40 669 FSWs were included in this analysis. The pooled proportion of FSWs initiating PrEP was 70% (95% CI: 56% to 85%) in studies that reported on facility-based models and 49% (95% CI: 10% to 87%) in community-based models. At 6 months, the pooled proportion of FSWs retained was 66% (95% CI: 15% to 100%) for facility-based models and 83% (95% CI: 75% to 91%) for community-based models. Factors associated with increased PrEP uptake were visiting a sex worker programme (adjusted OR (aOR) 2.92; 95% CI: 1.91 to 4.46), having ≥10 clients per day (aOR 1.71; 95% CI: 1.06 to 2.76) and lack of access to free healthcare in government-run health clinics (relative risk: 1.16; 95% CI: 1.06 to 1.26).
CONCLUSIONS
A hybrid approach incorporating both facility-based strategies for increasing uptake and community-based strategies for improving retention and adherence may effectively improve PrEP coverage among FSWs.
PROSPERO REGISTRATION NUMBER
CRD42020219363.
Topics: Humans; Sex Workers; Female; Pre-Exposure Prophylaxis; HIV Infections; Africa South of the Sahara; Medication Adherence; Anti-HIV Agents
PubMed: 38670600
DOI: 10.1136/bmjopen-2023-076545 -
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 -
International Health May 2024We performed a systematic review to generate evidence on the association between cumulative human immunodeficiency virus (HIV) viraemia and health outcomes.
BACKGROUND
We performed a systematic review to generate evidence on the association between cumulative human immunodeficiency virus (HIV) viraemia and health outcomes.
METHODS
Quantitative studies reporting on HIV cumulative viraemia (CV) and its association with health outcomes among people living with HIV (PLHIV) on antiretroviral treatment (ART) were included. We searched MEDLINE via PubMed, Embase, Scopus and Web of Science and conference abstracts from 1 January 2008 to 1 August 2022.
RESULTS
The systematic review included 26 studies. The association between CV and mortality depended on the study population, methods used to calculate CV and its level. Higher CV was not consistently associated with greater risk of acquire immunodeficiency syndrome-defining clinical conditions. However, four studies present a strong relationship between CV and cardiovascular disease. The risk was not confirmed in relation of increased hazards of stroke. Studies that assessed the effect of CV on the risk of cancer reported a positive association between CV and malignancy, although the effect may differ for different types of cancer.
CONCLUSIONS
CV is associated with adverse health outcomes in PLHIV on ART, especially at higher levels. However, its role in clinical and programmatic monitoring and management of PLHIV on ART is yet to be established.
Topics: Humans; HIV Infections; Viremia; Anti-HIV Agents; Anti-Retroviral Agents
PubMed: 37823452
DOI: 10.1093/inthealth/ihad093 -
Nutrients May 2024Palmitoylethanolamide (PEA) emerged over the years as a promising approach in the management of chronic pain. Despite the fact that the efficacy of micron-size PEA... (Meta-Analysis)
Meta-Analysis Review
Palmitoylethanolamide (PEA) emerged over the years as a promising approach in the management of chronic pain. Despite the fact that the efficacy of micron-size PEA formulations appears to be time-dependent, the optimal timing has not yet been elucidated. This systematic review and meta-analysis aim to estimate the possible advantage of an extended treatment in the relief of chronic pain. The literature search was conducted consulting scientific databases, to identify clinical trials in which micron-size PEA was administered for at least 60 days, and pain assessed by the Visual Analogue Scale (VAS) or Numeric Rating Scale (NRS). Nine studies matched the required criteria, for a total of 742 patients involved. The meta-analysis showed a statistically and clinically significant pain intensity reduction after 60 days of micron-size PEA supplementation, compared to 30 days (1.36 points, < 0.01). The secondary analysis revealed a weighted NRS/VAS score decrease of 2.08 points within the first month of treatment. These two obtained scores corresponded to a 35.1% pain intensity reduction within the first month, followed by a further 35.4% during the second month. Overall, these results confirm the clinically relevant and time-depended pain-relieving effect of micron-size PEA and therefore the advantage of an extended treatment, especially in patient with incomplete pain management.
Topics: Palmitic Acids; Humans; Amides; Ethanolamines; Chronic Pain; Pain Measurement; Administration, Oral; Treatment Outcome; Analgesics
PubMed: 38892586
DOI: 10.3390/nu16111653 -
BMJ Open Nov 2023As countries have scaled up access to antiretroviral therapy (ART) for HIV, attrition rates of up to 30% annually have created a large pool of individuals who initiate...
OBJECTIVES
As countries have scaled up access to antiretroviral therapy (ART) for HIV, attrition rates of up to 30% annually have created a large pool of individuals who initiate treatment with prior ART experience. Little is known about the proportion of non-naïve reinitiators within the population presenting for treatment initiation.
DESIGN
Systematic review of published articles and abstracts reporting proportions of non-naïve adult patients initiating ART in sub-Saharan Africa.
DATA SOURCES
PubMed, Embase Elsevier, Web of Science Core Collection, International AIDS Society conferences, Conference on Retroviruses and Opportunistic Infections conferences.
ELIGIBILITY CRITERIA
Clinical trials and observational studies; reporting on adults in sub-Saharan Africa who initiated lifelong ART; published in English between 1 January 2018 and 11 July 2023 and with data collected after January 2016. Initiator self-report, laboratory discernment of antiretroviral metabolites, and viral suppression at initiation or in the medical record were accepted as evidence of prior exposure.
DATA EXTRACTION AND SYNTHESIS
We captured study and sample characteristics, proportions with previous ART exposure and the indicator of previous exposure reported. We report results of each eligible study, estimate the risk of bias and identify gaps in the literature.
RESULTS
Of 2740 articles, 11 articles describing 12 cohorts contained sufficient information for the review. Proportions of initiators with evidence of prior ART use ranged from 5% (self-report only) to 53% (presence of ART metabolites in hair or blood sample). The vast majority of screened studies did not report naïve/non-naïve status. Metrics used to determine and report non-naïve proportions were inconsistent and difficult to interpret.
CONCLUSIONS
The proportion of patients initiating HIV treatment who are truly ART naïve is not well documented. It is likely that 20%-50% of ART patients who present for ART are reinitiators. Standard reporting metrics and diligence in reporting are needed, as is research to understand the reluctance of patients to report prior ART exposure.
PROSPERO REGISTRATION NUMBER
CRD42022324136.
Topics: Humans; Adult; Anti-HIV Agents; HIV Infections; Anti-Retroviral Agents; Health Services Accessibility; Africa South of the Sahara
PubMed: 37984944
DOI: 10.1136/bmjopen-2022-071283 -
Journal of Veterinary Internal Medicine 2024Equine herpes virus type 1 (EHV-1) infection in horses is associated with upper respiratory disease, neurological disease, abortions, and neonatal death. (Review)
Review
BACKGROUND
Equine herpes virus type 1 (EHV-1) infection in horses is associated with upper respiratory disease, neurological disease, abortions, and neonatal death.
REVIEW QUESTION
Does pharmacological therapy decrease either the incidence or severity of disease or infection caused by EHV-1 in domesticated horses?
METHODS
A systematic review was preformed searching AGRICOLA, CAB Abstracts, Cochrane, PubMed, Web of Science, and WHO Global Health Index Medicus Regional Databases to identify articles published before February 15, 2021. Selection criteria were original research reports published in peer reviewed journals, and studies investigating in vivo use of therapeutic agents for prevention or treatment of EHV-1 in horses. Outcomes assessed included measures related to clinical outcomes that reflect symptomatic EHV-1 infection or virus infection. We evaluated risk of bias and performed a GRADE evaluation of the quality of evidence for interventions.
RESULTS
A total of 7009 unique studies were identified, of which 9 met the inclusion criteria. Two studies evaluated valacyclovir or small interfering RNAs, and single studies evaluated the use of a Parapoxvirus ovis-based immunomodulator, human alpha interferon, an herbal supplement, a cytosine analog, and heparin. The level of evidence ranged between randomized controlled studies and observational trials. The risk of bias was moderate to high and sample sizes were small. Most studies reported either no benefit or minimal efficacy of the intervention tested.
CONCLUSIONS AND CLINICAL IMPORTANCE
Our review indicates minimal or limited benefit either as a prophylactic or post-exposure treatment for any of the studied interventions in the mitigation of EHV-1-associated disease outcome.
Topics: Animals; Horses; Herpesvirus 1, Equid; Horse Diseases; Herpesviridae Infections; Antiviral Agents; Valacyclovir
PubMed: 38380685
DOI: 10.1111/jvim.17016 -
Journal of Preventive Medicine and... Jan 2024The effectiveness and efficiency of pre-exposure prophylaxis (PrEP) in reducing the transmission of human immunodeficiency virus (HIV) among men who have sex with men... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The effectiveness and efficiency of pre-exposure prophylaxis (PrEP) in reducing the transmission of human immunodeficiency virus (HIV) among men who have sex with men (MSM) relies on how widely it is adopted and adhered to, particularly among high-risk groups of MSM. The meta-analysis aimed to collect and analyze existing evidence on various factors related to PrEP adherence in MSM, including demographic characteristics, sexual behaviors, substance use, and psychosocial factors.
METHODS
The meta-analysis followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The search included articles published between January 2018 and December 2022, obtained from the PubMed, ScienceDirect, and Scopus databases. The studies that were included in the analysis reported the proportion of MSM who demonstrated adherence to PrEP and underwent quality appraisal using the Newcastle-Ottawa Scale.
RESULTS
Of the 268 studies initially identified, only 12 met the inclusion criteria and were included in the final meta-analysis. The findings indicated that education (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.12 to 2.40), number of sexual partners (OR, 1.16; 95% CI, 1.02 to 1.31), engaging in sexual activities with an human immunodeficiency virus-positive partner (OR, 1.59; 95% CI, 1.16 to 2.26), substance use (OR, 0.83; 95% CI, 0.70 to 0.99), and lower levels of depression (OR, 0.55; 95% CI, 0.37 to 0.82) were associated with higher rates of PrEP adherence among MSM.
CONCLUSIONS
Despite these findings, further research is necessary to investigate PrEP adherence more comprehensively. The findings of this meta-analysis can be utilized to inform interventions aimed at improving PrEP adherence among MSM and provide directions for future research in this area.
Topics: Male; Humans; Homosexuality, Male; Pre-Exposure Prophylaxis; Safe Sex; HIV Infections; Anti-HIV Agents; Sexual and Gender Minorities; Sexual Behavior; Substance-Related Disorders
PubMed: 38147821
DOI: 10.3961/jpmph.23.345