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Hematology (Amsterdam, Netherlands) Dec 2024To explore the efficacy and safety of venetoclax-based combination therapy for older patients with newly diagnosed acute myeloid leukemia (AML). (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To explore the efficacy and safety of venetoclax-based combination therapy for older patients with newly diagnosed acute myeloid leukemia (AML).
METHODS
We performed a systematic review and meta-analysis of clinical trials comparing venetoclax plus hypomethylating agents (HMAs) or low-dose cytarabine (LDAC) with mono-HMAs or LDAC. The random or fixed effects model was applied to the studies based on heterogeneity. Dichotomous data were summarized using the risk ratio (RR) and 95% confidence interval (CI). Continuous variable data were reported as weighted mean differences (WMDs).
RESULTS
Nine studies, including a total of 1232 patients, were included in this meta-analysis. Thec complete remission (CR)/complete remission with incomplete hematological recovery (CRi) rate of the venetoclax (Ven) + azacytidine (Aza) group was significantly greater than that of the Aza monotherapy group (RR: 2.42; 95% CI: 1.85-3.15; < 0.001). Similarly, the CR/CRi rate of the Ven + LDAC group was also significantly greater than that of the LDAC monotherapy group (RR: 2.57; 95% CI: 1.58-4.17; = 0.00). The same results were observed for OS among these groups. However, the incidence of febrile neutropenia was greater in the Ven + Aza group than in the Ven + Decitabine (Dec) or monotherapy Aza group (RR: 0.69; 95% CI: 0.53-0.90; = 0.006 and RR: 2.19; 95% CI: 1.58-3.03; < 0.001, respectively). In addition, the Ven + LDAC group had significantly greater rates of constipation, diarrhea, nausea, and vomiting than the LDAC monotherapy group, with RRs and CIs of 0.61 (95% CI 0.44-0.83, = 0.002), 1.81 (95% CI 1.22-2.67, = 0.003), 1.39 (95% CI 1.06-1.82, = 0.016), and 1.80 (95% CI 1.19-2.72, = 0.005), respectively.
CONCLUSION
Venetoclax combined with azacitidine, decitabine, or LDAC significantly improved the CR/CRi and OS of patients with previously untreated AML. However, venetoclax plus azacitidine or LDAC was more likely to lead to increased febrile neutropenia and gastrointestinal toxicity.
Topics: Humans; Bridged Bicyclo Compounds, Heterocyclic; Sulfonamides; Leukemia, Myeloid, Acute; Antineoplastic Combined Chemotherapy Protocols; Azacitidine; Treatment Outcome; Aged; Cytarabine
PubMed: 38703055
DOI: 10.1080/16078454.2024.2343604 -
BMC Infectious Diseases May 2024Despite antiretroviral treatment (ART), the human immunodeficiency virus (HIV) continues to pose a considerable health burden in resource-poor countries. This systematic... (Meta-Analysis)
Meta-Analysis
Mortality and its predictors among human immunodeficiency virus-infected children younger than 15 years receiving antiretroviral therapy in Ethiopia: a systematic review and meta-analysis.
BACKGROUND
Despite antiretroviral treatment (ART), the human immunodeficiency virus (HIV) continues to pose a considerable health burden in resource-poor countries. This systematic review and meta-analysis aimed to determine the pooled incidence density of mortality and identify potential predictors among HIV-infected children receiving ART, from studies conducted in various parts of Ethiopia.
METHODS
A comprehensive database search was made in Excerpta Medica, PubMed, Web of Science, African Journals Online, Google Scholar, and Scopus. We reported results following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020. Excel Spreadsheet and STATA Version 14 software were used for data abstraction and meta-analysis, respectively. Statistical heterogeneity among studies was assessed using I statistics. Meta-regression and subgroup analysis were performed to further explore the sources of statistical heterogeneity. Moreover, publication bias and a leave-out-one sensitivity analysis were performed.
RESULTS
Twenty-two articles involving 8,731 participants met inclusion criteria and were included. The pooled incidence density of mortality was 3.08 (95% confidence interval (CI), 2.52 to 3.64) per 100 child years. Predictors of mortality were living in rural areas (hazard ratio (HR), 2.18 [95% CI, 1.20 to 3.98]), poor adherence to ART (HR, 2.85 [ 95% CI, 1.39 to 5.88]), failure to initiate co-trimoxazole preventive therapy (HR, 2.16 [95% CI, 1.52 to 3.07]), anemia (HR, 2.28 [95% CI, 1.51 to 3.45]), opportunistic infections (HR, 1.52 [ 95% CI, 1.15 to 2.00]), underweight (HR, 1.74 [95% CI, 1.26 to 2.41]), wasting (HR, 2.54 [95% CI, 1.56 to 4.16]), stunting (HR, 2.02 [95% CI, 1.63 to 2.51]), World Health Organization classified HIV clinical stages III and IV (HR, 1.71 [95% CI, 1.42 to 2.05]), and Nevirapine-based regimens (HR, 3.91 [95% CI, 3.09 to 4.95]).
CONCLUSIONS
This study found that the overall mortality rate among HIV-infected children after ART initiation was high. Therefore, high-level commitment and involvement of responsible caregivers, healthcare providers, social workers, and program managers are of paramount importance to identify these risk factors and thus enhance the survival of HIV-infected children receiving ART.
Topics: Humans; Ethiopia; HIV Infections; Child; Child, Preschool; Adolescent; Infant; Anti-HIV Agents; Female; Male; Incidence; Anti-Retroviral Agents; Risk Factors
PubMed: 38702591
DOI: 10.1186/s12879-024-09366-1 -
The Cochrane Database of Systematic... May 2024The risk of cytomegalovirus (CMV) infection in solid organ transplant recipients has resulted in the frequent use of prophylaxis to prevent the clinical syndrome... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The risk of cytomegalovirus (CMV) infection in solid organ transplant recipients has resulted in the frequent use of prophylaxis to prevent the clinical syndrome associated with CMV infection. This is an update of a review first published in 2005 and updated in 2008 and 2013.
OBJECTIVES
To determine the benefits and harms of antiviral medications to prevent CMV disease and all-cause death in solid organ transplant recipients.
SEARCH METHODS
We contacted the information specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 5 February 2024 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs comparing antiviral medications with placebo or no treatment, comparing different antiviral medications or different regimens of the same antiviral medications for CMV prophylaxis in recipients of any solid organ transplant. Studies examining pre-emptive therapy for CMV infection are studied in a separate review and were excluded from this review.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed study eligibility, risk of bias and extracted data. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
MAIN RESULTS
This 2024 update found four new studies, bringing the total number of included studies to 41 (5054 participants). The risk of bias was high or unclear across most studies, with a low risk of bias for sequence generation (12), allocation concealment (12), blinding (11) and selective outcome reporting (9) in fewer studies. There is high-certainty evidence that prophylaxis with aciclovir, ganciclovir or valaciclovir compared with placebo or no treatment is more effective in preventing CMV disease (19 studies: RR 0.42, 95% CI 0.34 to 0.52), all-cause death (17 studies: RR 0.63, 95% CI 0.43 to 0.92), and CMV infection (17 studies: RR 0.61, 95% CI 0.48 to 0.77). There is moderate-certainty evidence that prophylaxis probably reduces death from CMV disease (7 studies: RR 0.26, 95% CI 0.08 to 0.78). Prophylaxis reduces the risk of herpes simplex and herpes zoster disease, bacterial and protozoal infections but probably makes little to no difference to fungal infection, acute rejection or graft loss. No apparent differences in adverse events with aciclovir, ganciclovir or valaciclovir compared with placebo or no treatment were found. There is high certainty evidence that ganciclovir, when compared with aciclovir, is more effective in preventing CMV disease (7 studies: RR 0.37, 95% CI 0.23 to 0.60). There may be little to no difference in any outcome between valganciclovir and IV ganciclovir compared with oral ganciclovir (low certainty evidence). The efficacy and adverse effects of valganciclovir or ganciclovir were probably no different to valaciclovir in three studies (moderate certainty evidence). There is moderate certainty evidence that extended duration prophylaxis probably reduces the risk of CMV disease compared with three months of therapy (2 studies: RR 0.20, 95% CI 0.12 to 0.35), with probably little to no difference in rates of adverse events. Low certainty evidence suggests that 450 mg/day valganciclovir compared with 900 mg/day valganciclovir results in little to no difference in all-cause death, CMV infection, acute rejection, and graft loss (no information on adverse events). Maribavir may increase CMV infection compared with ganciclovir (1 study: RR 1.34, 95% CI: 1.10 to 1.65; moderate certainty evidence); however, little to no difference between the two treatments were found for CMV disease, all-cause death, acute rejection, and adverse events at six months (low certainty evidence).
AUTHORS' CONCLUSIONS
Prophylaxis with antiviral medications reduces CMV disease and CMV-associated death, compared with placebo or no treatment, in solid organ transplant recipients. These data support the continued routine use of antiviral prophylaxis in CMV-positive recipients and CMV-negative recipients of CMV-positive organ transplants.
Topics: Humans; Acyclovir; Antiviral Agents; Bias; Cause of Death; Cytomegalovirus Infections; Ganciclovir; Organ Transplantation; Postoperative Complications; Randomized Controlled Trials as Topic; Transplant Recipients; Valacyclovir; Valganciclovir
PubMed: 38700045
DOI: 10.1002/14651858.CD003774.pub5 -
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 -
Viruses Mar 2024The post-transcriptional regulatory element (PRE) is present in all HBV mRNAs and plays a major role in their stability, nuclear export, and enhancement of viral gene... (Review)
Review
The post-transcriptional regulatory element (PRE) is present in all HBV mRNAs and plays a major role in their stability, nuclear export, and enhancement of viral gene expression. Understanding PRE's structure, function, and mode of action is essential to leverage its potential as a therapeutic target. A wide range of PRE-based reagents and tools have been developed and assessed in preclinical and clinical settings for therapeutic and biotechnology applications. This manuscript aims to provide a systematic review of the characteristics and mechanism of action of PRE, as well as elucidating its current applications in basic and clinical research. Finally, we discuss the promising opportunities that PRE may provide to antiviral development, viral biology, and potentially beyond.
Topics: Animals; Humans; Antiviral Agents; Gene Expression Regulation, Viral; Hepatitis B; Hepatitis B virus; RNA Processing, Post-Transcriptional; RNA, Messenger; RNA, Viral
PubMed: 38675871
DOI: 10.3390/v16040528 -
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 -
PloS One 2024The prevalence of hepatitis C virus (HCV) among people who inject drugs (PWID) is between 50-70%. Prior systematic reviews demonstrated that PWID have similar direct... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The prevalence of hepatitis C virus (HCV) among people who inject drugs (PWID) is between 50-70%. Prior systematic reviews demonstrated that PWID have similar direct acting antiviral treatment outcomes compared to non-PWID; however, reviews have not examined treatment outcomes by housing status. Given the links between housing and health, identifying gaps in HCV treatment can guide future interventions.
METHODS
We conducted a systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched six databases for articles from 2014 onward. Two reviewers conducted title/abstract screenings, full-text review, and data extraction. We extracted effect measures for treatment initiation, adherence, completion, success, and reinfection by housing status. Studies underwent quality and certainty assessments, and we performed meta-analyses as appropriate.
RESULTS
Our search yielded 473 studies, eight of which met inclusion criteria. Only the treatment initiation outcome had sufficient measures for meta-analysis. Using a random-effects model, we found those with unstable housing had 0.40 (0.26, 0.62) times the odds of initiating treatment compared to those with stable housing. Other outcomes were not amenable for meta-analysis due to a limited number of studies or differing outcome definitions.
CONCLUSIONS
Among PWID, unstable housing appears to be a barrier to HCV treatment initiation; however, the existing data is limited for treatment initiation and the other outcomes we examined. There is a need for more informative studies to better understand HCV treatment among those with unstable housing. Specifically, future studies should better define housing status beyond a binary, static measure to capture the nuances and complexity of housing and its subsequent impact on HCV treatment. Additionally, researchers should meaningfully consider whether the outcome(s) of interest are being accurately measured for individuals experiencing unstable housing.
Topics: Humans; Hepatitis C; Housing; Substance Abuse, Intravenous; Treatment Outcome; Antiviral Agents; Hepacivirus
PubMed: 38669250
DOI: 10.1371/journal.pone.0302471 -
Journal of Investigative Medicine : the... May 2024Advances in human immunodeficiency virus (HIV) treatment, including combination antiretroviral therapy (cART), have transformed HIV into a chronic condition. Kidney... (Review)
Review
Advances in human immunodeficiency virus (HIV) treatment, including combination antiretroviral therapy (cART), have transformed HIV into a chronic condition. Kidney diseases cause morbidity and mortality in patients living with HIV (PLWH), though cART has permitted kidney transplants with acceptable post-transplant graft and patient survival. Risk of allograft rejection remains high, which may be related to interactions between cART, specifically protease inhibitors (PI), and immunosuppressants prescribed post-transplant. This systematic review evaluates renal transplant outcomes in PLWH treated with PI- vs non-PI-based cART. A search strategy was generated with terms related to renal transplant, HIV, and cART and run on PubMed, Embase, Scopus, and Cochrane. Studies were evaluated using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines on Covidence by two reviewers and then evaluated for bias. Of 803 studies, 9 were included. Included papers were prospective or retrospective cohort studies or chart reviews of adult patients. Outcome measures included acute graft rejection, graft survival, and patient survival. One study had significant results demonstrating that PI-based therapy was correlated with increased graft rejection rates. Two studies demonstrated significant graft survival benefit to non-PI-based therapy, while one demonstrated significant benefit to PI-based therapy. Two studies found significant patient survival benefit to non-PI-based therapy. For each outcome measure, remaining data suggested improved outcomes with non-PI-based therapies without achieving statistical significance. The results demonstrate superior outcomes in PLWH taking non-PI-based cART, though the paucity of significant results suggests that PLWH who require PI-based cART for virological control may continue their regimen safely post-kidney transplant.
PubMed: 38666448
DOI: 10.1177/10815589241252595 -
PloS One 2024Despite policy initiatives and strategic measures highly focused on preventing mother-to-child transmission through the implementation of the Option B+ program,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite policy initiatives and strategic measures highly focused on preventing mother-to-child transmission through the implementation of the Option B+ program, adherence to the treatment is still challenging. The level of adherence and determinants of Option B+ program utilization reported by different studies were highly inconsistent in Ethiopia. Hence, this systematic review and meta-analysis aimed to estimate the pooled prevalence of adherence to the Option B+ program and its predictors among HIV-positive women in Ethiopia.
METHODS
PubMed, Google Scholar, EMBASE, HINAR, Scopus, and Web of Sciences were searched for published articles from March 2010 to March 2022. The pooled prevalence of adherence was estimated using a weighted DerSimonian-Laird random effect model. The I2 statistics was used to identify the degree of heterogeneity. Publication bias was also assessed using the funnel plot and Egger's regression test.
RESULTS
A total of 15 studies were included. The pooled estimate of the option B+ program among HIV-positive women in Ethiopia was 81.58% (95% CI: 77.33-85.84). Getting social and financial support (AOR = 3.73, 95% CI: 2.12, 6.58), disclosure of HIV status to partners (AOR = 2.05, 95% CI: 1.75, 2.41), time to reach a health facility (AOR = 0.33, 95% CI: 0.16, 0.67), receiving counseling on drug side effects (AOR = 4.09, 95% CI: 2.74, 6.11), experience of drug side effects (AOR = 0.17, 95% CI: 0.08, 0.36), and knowledge (AOR = 4.73, 95% CI: 2.62, 8.51) were significantly associated with adherence to the Option B+ program.
CONCLUSION
This meta-analysis showed that the level of adherence to the Option B+ program in Ethiopia is lower than the 95% level of adherence planned to be achieved in 2020. Social and financial support, disclosure of HIV status, time to reach the health facility, counseling, drug side effects, and knowledge of PMTCT were significantly associated with option B+ adherence. The findings of this meta-analysis highlight that governmental, non-governmental, and other stakeholders need to design an effective strategy to scale up the level of disclosing one's own HIV status, access health facilities, improve knowledge of PMTCT, and counsel the potential side effects of Option B+ drugs, and advocate the program to reduce the multidimensional burden of HIV/AIDS.
TRIAL REGISTRATION
Prospero registration: CRD42022320947. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022320947.
Topics: Humans; Ethiopia; Female; HIV Infections; Infectious Disease Transmission, Vertical; Pregnancy; Anti-HIV Agents
PubMed: 38662634
DOI: 10.1371/journal.pone.0298119 -
Reviews in Medical Virology May 2024Serious adverse events following vaccination include medical complications that require hospitalisation. The live varicella vaccine that was approved by the Food and... (Review)
Review
Serious adverse events following vaccination include medical complications that require hospitalisation. The live varicella vaccine that was approved by the Food and Drug Administration in the United States in 1995 has an excellent safety record. Since the vaccine is a live virus, adverse events are more common in immunocompromised children who are vaccinated inadvertently. This review includes only serious adverse events in children considered to be immunocompetent. The serious adverse event called varicella vaccine meningitis was first reported in a hospitalised immunocompetent child in 2008. When we carried out a literature search, we found 15 cases of immunocompetent children and adolescents with varicella vaccine meningitis; the median age was 11 years. Eight of the children had received two varicella vaccinations. Most of the children also had a concomitant herpes zoster rash, although three did not. The children lived in the United States, Greece, Germany, Switzerland, and Japan. During our literature search, we found five additional cases of serious neurological events in immunocompetent children; these included 4 cases of progressive herpes zoster and one case of acute retinitis. Pulses of enteral corticosteroids as well as a lack of herpes simplex virus antibody may be risk factors for reactivation in immunocompetent children. All 20 children with adverse events were treated with acyclovir and recovered; 19 were hospitalised and one child was managed as an outpatient. Even though the number of neurological adverse events remains exceedingly low following varicella vaccination, we recommend documentation of those caused by the vaccine virus.
Topics: Adolescent; Child; Child, Preschool; Female; Humans; Male; Acyclovir; Antiviral Agents; Chickenpox; Chickenpox Vaccine; Herpesvirus 3, Human; Meningitis, Viral; Nervous System Diseases; Vaccination; Virus Activation
PubMed: 38658176
DOI: 10.1002/rmv.2538