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Annals of Clinical Microbiology and... Aug 2023Since the beginning of the COVID-19 pandemic, therapeutic options for treating COVID-19 have been investigated at different stages of clinical manifestations.... (Review)
Review
Pan-American Guidelines for the treatment of SARS-CoV-2/COVID-19: a joint evidence-based guideline of the Brazilian Society of Infectious Diseases (SBI) and the Pan-American Association of Infectious Diseases (API).
BACKGROUND
Since the beginning of the COVID-19 pandemic, therapeutic options for treating COVID-19 have been investigated at different stages of clinical manifestations. Considering the particular impact of COVID-19 in the Americas, this document aims to present recommendations for the pharmacological treatment of COVID-19 specific to this population.
METHODS
Fifteen experts, members of the Brazilian Society of Infectious Diseases (SBI) and the Pan-American Association of Infectious Diseases (API) make up the panel responsible for developing this guideline. Questions were formulated regarding prophylaxis and treatment of COVID-19 in outpatient and inpatient settings. The outcomes considered in decision-making were mortality, hospitalisation, need for mechanical ventilation, symptomatic COVID-19 episodes, and adverse events. In addition, a systematic review of randomised controlled trials was conducted. The quality of evidence assessment and guideline development process followed the GRADE system.
RESULTS
Nine technologies were evaluated, and ten recommendations were made, including the use of tixagevimab + cilgavimab in the prophylaxis of COVID-19, tixagevimab + cilgavimab, molnupiravir, nirmatrelvir + ritonavir, and remdesivir in the treatment of outpatients, and remdesivir, baricitinib, and tocilizumab in the treatment of hospitalised patients with severe COVID-19. The use of hydroxychloroquine or chloroquine and ivermectin was discouraged.
CONCLUSION
This guideline provides recommendations for treating patients in the Americas following the principles of evidence-based medicine. The recommendations present a set of drugs that have proven effective in the prophylaxis and treatment of COVID-19, emphasising the strong recommendation for the use of nirmatrelvir/ritonavir in outpatients as the lack of benefit from the use of hydroxychloroquine and ivermectin.
Topics: Humans; United States; COVID-19; SARS-CoV-2; Ritonavir; Hydroxychloroquine; Pandemics; Brazil; Ivermectin; Communicable Diseases; Antiviral Agents
PubMed: 37550690
DOI: 10.1186/s12941-023-00623-w -
The Journal of Infectious Diseases Aug 2023This study aims to comparatively analyze clinical features, treatment, and patient outcomes between the previous and the 2022 mpox (monkeypox) outbreaks. (Meta-Analysis)
Meta-Analysis
BACKGROUND
This study aims to comparatively analyze clinical features, treatment, and patient outcomes between the previous and the 2022 mpox (monkeypox) outbreaks.
METHODS
Five bibliographic databases were searched for studies reporting clinical features, management, and patient outcomes of mpox. Systematic review and meta-analysis were performed.
RESULTS
In total, 73 studies were included in the systematic review, of which 33 studies were subjected to meta-analysis. Previous outbreaks substantially affected children, whereas the 2022 outbreak primarily affected male adults, of which 94.66% (95% confidence interval [CI], 88.03-98.95) were men who have sex with men. Furthermore, 72.47% (95% CI, 51.04-89.71) reported high-risk sexual activity and the overall human immunodeficiency virus (HIV) prevalence was 37.65% (95% CI, 30.09-45.50). Skin lesions remain the typical symptom; however, their anatomic distribution differed. Systemic manifestations were common, but rectal pain was unique to the 2022 outbreak. The estimated overall fatality during past outbreaks in Africa was 4.61% (95% CI, 2.39%-7.35%), whereas 6.34% (95% CI, 3.35%-10.10%) of patients from the 2022 outbreak required hospitalization. Antiviral treatment, in particular tecovirimat, has been prescribed for a subset of patients, but the efficacy remains inconclusive.
CONCLUSIONS
These findings are important for better understanding the disease and guiding adequate response to mpox outbreaks.
Topics: Adult; Child; Humans; Male; Female; Homosexuality, Male; Mpox (monkeypox); Sexual and Gender Minorities; Antiviral Agents; Disease Outbreaks; Pelvic Pain
PubMed: 36735342
DOI: 10.1093/infdis/jiad034 -
PloS One 2024The aim of this study was to assess the effectiveness and safety of azvudine in treating coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The aim of this study was to assess the effectiveness and safety of azvudine in treating coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2).
METHODS
A search was carried out in PubMed, Cochrane Library, Web of Science, medRxiv, and Google Scholar until October 20, 2023. The Cochrane risk of bias tools were used to assess the quality of included studies. Comprehensive Meta-Analysis software was used to analyze data.
RESULTS
Twenty-one studies including 10,011 patients were examined. The meta-analysis results showed that azvudine and standard of care/placebo (SOC/PBO) were significantly different concerning mortality rate (risk ratio [RR] = 0.48, 95% confidence interval [CI]: 0.40 to 0.57) and negative polymerase chain reaction (PCR) conversion time (standard mean difference = - 0.75, 95% CI: -1.29 to-0.21). However, the two groups did not show significant differences concerning hospital stay, intensive care unit (ICU) admission, and need for mechanical ventilation (P > 0.05). On the other hand, azvudine and nirmatrelvir-ritonavir were significantly different in mortality rate (RR = 0.73, 95% CI: 0.58 to 0.92), ICU admission (RR = 0.41, 95% CI: 0.21 to 0.78), and need for mechanical ventilation (RR = 0.67, 95% CI: 0.51 to 0.89), but the two treatments were not significantly different in negative PCR conversion time, and hospital stay (P > 0.05). The incidence of adverse events between groups was not significant (P > 0.05). The certainty of evidence was rated as low or moderate.
CONCLUSIONS
The antiviral effectiveness of azvudine against SARS-COV-2 is questionable with regard to the certainty of evidence. Further research should be conducted to establish the effectiveness and safety of azvudine in COVID-19.
Topics: Humans; COVID-19 Drug Treatment; Antiviral Agents; SARS-CoV-2; COVID-19; Treatment Outcome
PubMed: 38870134
DOI: 10.1371/journal.pone.0298772 -
The American Journal of Tropical... Jan 2024Seasonal malaria chemoprevention (SMC) for children under 5 years of age for up to four monthly cycles during malaria transmission season was recommended by the WHO in... (Meta-Analysis)
Meta-Analysis
Seasonal malaria chemoprevention (SMC) for children under 5 years of age for up to four monthly cycles during malaria transmission season was recommended by the WHO in 2012 and has been implemented in 13 countries in the Sahel, reaching more than 30 million children annually. Malaria control programs implementing SMC have asked the WHO to consider expanding the age range or number of monthly cycles. We conducted a systematic review and meta-analysis of SMC among children up to 15 years of age and up to six monthly cycles. Twelve randomized studies were included, with outcomes stratified by age (< 5/≥ 5 years), by three or four versus five or six cycles, and by drug where possible. Drug regimens included sulfadoxine-pyrimethamine + amodiaquine, amodiaquine-artesunate, and sulfadoxine-pyrimethamine + artesunate. Included studies were all conducted in Sahelian countries in which high-grade resistance to sulfadoxine-pyrimethamine was rare and in zones with parasite prevalence ranging from 1% to 79%. Seasonal malaria chemoprevention resulted in substantial reductions in uncomplicated malaria incidence measured during that transmission season (rate ratio: 0.27, 95% CI: 0.25-0.29 among children < 5 years; rate ratio: 0.27, 95% CI: 0.25-0.30 among children ≥ 5 years) and in the prevalence of malaria parasitemia measured within 4-6 weeks from the final SMC cycle (risk ratio: 0.38, 95% CI: 0.34-0.43 among children < 5 years; risk ratio: 0.23, 95% CI: 0.11-0.48 among children ≥ 5 years). In high-transmission zones, SMC resulted in a moderately reduced risk of any anemia (risk ratio: 0.77, 95% CI: 0.72-0.83 among children < 5 years; risk ratio: 0.70, 95% CI: 0.52-0.95 among children ≥ 5 years [one study]). Children < 10 years of age had a moderate reduction in severe malaria (risk ratio: 0.53, 95% CI: 0.37-0.76) but no evidence of a mortality reduction. The evidence suggests that in areas in which sulfadoxine-pyrimethamine and amodiaquine remained efficacious, SMC effectively reduced malaria disease burden among children both < 5 and ≥ 5 years old and that the number of cycles should be commensurate with the length of the transmission season, up to six cycles.
Topics: Child; Child, Preschool; Humans; Amodiaquine; Antimalarials; Artesunate; Chemoprevention; Drug Combinations; Malaria; Pyrimethamine; Seasons; Sulfadoxine; Adolescent
PubMed: 38081050
DOI: 10.4269/ajtmh.23-0481 -
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 -
Virology Journal Oct 2023Ethiopia is among the highly HIV-affected countries, with reported 12,000 and 12,000 AIDS-related deaths and incidents as per reports from 2021. Although the country has... (Review)
Review
BACKGROUND
Ethiopia is among the highly HIV-affected countries, with reported 12,000 and 12,000 AIDS-related deaths and incidents as per reports from 2021. Although the country has made a promising progress in antiretroviral therapy, recent studies have indicated that pretreatment drug resistance (PDR) is alarmingly increasing, which has become a challenge for the effectiveness of HIV treatment. Epidemiologic data on PDR is necessary to help establish ART regimens with good efficacy. Thus, this systematic review aimed to determine the trend analysis of PDR among ART-naïve individuals along with HIV variant dynamics in Ethiopia.
METHOD
HIV-1 pol sequences from studies conducted between 2003 and 2018 among ART-naïve Ethiopian individuals were retrieved from GenBank and analyzed for the presence of PDR mutations (PDRM) along with the analysis of HIV-1 variant dynamics. The Calibrated Population Resistance (CPR) tool Version 8.1 and the REGA HIV-1 Subtyping Tool Version 3 were used to determine the PDRM and HIV-1 genetic diversity, respectively.
RESULT
We identified nine studies and analyzed 1070 retrieved HIV-1 pol sequences in this systematic review. The pooled prevalence of PDR was 4.8% (51/1070), including 1.4% (15/1070), 2.8% (30/1070), and 0.8% (9/1070) for nucleoside reverse transcriptase inhibitor (NRTI), non-NRTI (NNRTI), and protease inhibitor (PI) resistance, respectively. NRTI and NNRTI concurrent PDRM were observed among 0.2% (2/799) of the analyzed sequences. The overall PDR prevalence has been increasing over the years. Though the prevalence of the NNRTI, NRTI, and PI PDR also increased over the years, the NNRTI increment was more pronounced than the others, reaching 7.84% in 2018 from 2.19% in 2003. The majority (97%; 1038/1070) of the genetic diversity was HIV-1 subtype C virus, followed by subtype C' (2%; 20/1038) and other subtypes (1%; 10/1038).
CONCLUSIONS
According to this systematic review, the overall pooled prevalence of PDR is low. Despite the low prevalence, there has been an increasing trend of PDR over the years, which implies the need for routine surveillance of PDRMs along with preventive measures. Hence, this supports the recently endorsed transition of ART regimens from NNRTI to integrase strand transfer inhibitor-based regimens recommended by the WHO. In addition, this finding underscores the need for routine baseline genotypic drug resistance testing for all newly diagnosed HIV-infected patients before initiating treatment to halt the upward trend of PDR.
Topics: Humans; HIV-1; Anti-HIV Agents; HIV Infections; Reverse Transcriptase Inhibitors; HIV Seropositivity; Mutation; Genotype; Drug Resistance, Viral; Prevalence; Sequence Analysis
PubMed: 37880705
DOI: 10.1186/s12985-023-02205-w -
Revista Paulista de Pediatria : Orgao... 2023To investigate the impact of tenofovir disoproxil fumarate on bone mineral density and bone mineral content in children and adolescents infected with the human...
OBJECTIVE
To investigate the impact of tenofovir disoproxil fumarate on bone mineral density and bone mineral content in children and adolescents infected with the human immunodeficiency virus.
DATA SOURCE
The search procedure was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. The search was carried out until April 2022 in Medical Literature Analysis and Retrieval System Online (Medline), Embase, Cochrane Central, Latin American and Caribbean Health Sciences Literature, Web of Science, Scopus, and MedRxiv. The combination of terms used was: (Children OR Youth OR Teenagers) AND HIV AND (Tenofovir OR "Antiretroviral therapy") AND ("Bone density" OR Osteoporosis OR Osteopenia). The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO, CRD42022312851).
DATA SYNTHESIS
The initial searches resulted in 1156 papers. After the exclusion of duplicate studies, three blinded reviewers analyzed the title and abstract of 563 papers, of which 57 remained to be read in full. Only nine papers met the eligibility criteria and were included in descriptive and risk-of-bias analyses. Regarding study design, four were cross-sectional, three were longitudinal before-after studies without a control group, and two were prospective cohorts. Among these nine papers, seven showed no significant association between tenofovir disoproxil fumarate use and reduced bone mass in young people. However, these papers did not have high methodological quality.
CONCLUSIONS
Although most of the selected papers found no harmful effect of tenofovir disoproxil fumarate on bone mass, further primary research with higher methodological quality is needed so robust scientific evidences can be obtained.
Topics: Adolescent; Humans; Child; Tenofovir; Bone Density; HIV; Adenine; HIV Infections
PubMed: 37971172
DOI: 10.1590/1984-0462/2024/42/2023042 -
Viruses Feb 2024There are an increasing number of articles focused on the prevalence and clinical impact of pretreatment HIV drug resistance (PDR) detected by Sanger sequencing (SGS).... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There are an increasing number of articles focused on the prevalence and clinical impact of pretreatment HIV drug resistance (PDR) detected by Sanger sequencing (SGS). PDR may contribute to the increased likelihood of virologic failure and the emergence of new resistance mutations. As SGS is gradually replaced by next-generation sequencing (NGS), it is necessary to assess the levels of PDR using NGS in ART-naïve patients systematically. NGS can detect the viral variants (low-abundance drug-resistant HIV-1 variants (LA-DRVs)) of virus quasi-species at levels below 20% that SGS may fail to detect. NGS has the potential to optimize current HIV drug resistance surveillance methods and inform future research directions. As the NGS technique has high sensitivity, it is highly likely that the level of pretreatment resistance would be underestimated using conventional techniques.
METHODS
For the systematic review and meta-analysis, we searched for original studies published in PubMed, Web of Science, Scopus, and Embase before 30 March 2023 that focused exclusively on the application of NGS in the detection of HIV drug resistance. Pooled prevalence estimates were calculated using a random effects model using the 'meta' package in R (version 4.2.3). We described drug resistance detected at five thresholds (>1%, 2%, 5%, 10%, and 20% of virus quasi-species). Chi-squared tests were used to analyze differences between the overall prevalence of PDR reported by SGS and NGS.
RESULTS
A total of 39 eligible studies were selected. The studies included a total of 15,242 ART-naïve individuals living with HIV. The prevalence of PDR was inversely correlated with the mutation detection threshold. The overall prevalence of PDR was 29.74% at the 1% threshold, 22.43% at the 2% threshold, 15.47% at the 5% threshold, 12.95% at the 10% threshold, and 11.08% at the 20% threshold. The prevalence of PDR to INSTIs was 1.22% (95%CI: 0.58-2.57), which is the lowest among the values for all antiretroviral drugs. The prevalence of LA-DRVs was 9.45%. At the 2% and 20% detection threshold, the prevalence of PDR was 22.43% and 11.08%, respectively. Resistance to PIs and INSTIs increased 5.52-fold and 7.08-fold, respectively, in those with a PDR threshold of 2% compared with those with PDR at 20%. However, resistance to NRTIs and NNRTIs increased 2.50-fold and 2.37-fold, respectively. There was a significant difference between the 2% and 5% threshold for detecting HIV drug resistance. There was no statistically significant difference between the results reported by SGS and NGS when using the 20% threshold for reporting resistance mutations.
CONCLUSION
In this study, we found that next-generation sequencing facilitates a more sensitive detection of HIV-1 drug resistance than SGS. The high prevalence of PDR emphasizes the importance of baseline resistance and assessing the threshold for optimal clinical detection using NGS.
Topics: Humans; HIV-1; Anti-HIV Agents; HIV Infections; Genotype; Drug Resistance, Viral; HIV Seropositivity; High-Throughput Nucleotide Sequencing; Prevalence; Mutation
PubMed: 38400015
DOI: 10.3390/v16020239 -
European Journal of Medical Research Jan 2024During the COVID-19 pandemic, some populations, including immunocompromised patients, could not tolerate COVID-19 vaccination or had low responses. Evusheld is a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
During the COVID-19 pandemic, some populations, including immunocompromised patients, could not tolerate COVID-19 vaccination or had low responses. Evusheld is a combined neutralizing monoclonal antibody containing tixagevimab and cilgavimab. The World Health Organization (WHO) has approved this combination as pre-exposure prophylaxis (PrEP) and treatment for immunocompromised patients. With the new variant, the (WHO) recommended an increase in dose from 300 to 600 mg with a booster dose after 6 months. The target of this review was to compare the efficacy of the two doses, 300 mg and 600 mg of tixagevimab/cilgavimab (Evusheld) as prophylaxis for higher-risk individuals to reveal if there is a significant difference in efficacy between those two doses of the drug.
METHODS
In this study, electronic databases (PubMed, Web of Science core collection, Scopus, and Cochran) were investigated for articles up to 31/12/2022 in English using a well-established search strategy. We included studies conducted in immunocompromised patients (aged ≥ 12 years) (WHO) received Evusheld as prophylaxis or treatment for COVID-19. After excluding studies inconsistent with the selection criteria, 24 were involved, 22 of which were included in the meta-analysis. We analyzed the data by using RevMan 5.4 program software.
RESULTS
In the double-arm subgroup analysis, Evusheld 600 mg, administered as prophylaxis, showed no significant difference in the COVID-19 infection rate, mortality rate, or needed hospitalization rate compared with the dose of 300 mg (p = 0.13, p = 0.29, and p = 0.25, respectively). In the single-arm subgroup analysis, Evusheld 600 mg, administered as prophylaxis, showed a significant decrease in the COVID-19 infection rate and the hospitalization rate compared with the dose of 300 mg (p = 0.0001, p = 0.007, respectively). As a treatment, Evusheld showed a significant decrease in the mortality rate over the placebo group (p = 0.01) in COVID-19 patients.
CONCLUSION
This result indicated that Evusheld was an effective prophylactic and therapeutic drug for COVID-19 infection, especially for immunocompromised patients, but there was no considerable variation between the high and low doses. Further prospective and randomized controlled trials (RCTs) with increased population sizes are necessary to show the valuable benefit of the high dose of Evusheld in COVID-19 prevention and treatment and to compare the difference between the two doses within adverse events.
Topics: Humans; Antibodies, Monoclonal; COVID-19; Immunocompromised Host; COVID-19 Drug Treatment; Drug Combinations; Antibodies, Neutralizing
PubMed: 38183123
DOI: 10.1186/s40001-023-01549-x -
BMC Pulmonary Medicine Nov 2023Numerous studies have demonstrated the potential of pirfenidone to enhance the prognosis of patients afflicted with idiopathic pulmonary fibrosis (IPF). Although... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Numerous studies have demonstrated the potential of pirfenidone to enhance the prognosis of patients afflicted with idiopathic pulmonary fibrosis (IPF). Although N-acetylcysteine (NAC) is utilized as an antioxidant in IPF treatment, the combination of NAC and pirfenidone has produced inconsistent outcomes in certain studies. To assess the clinical effectiveness and safety of NAC plus pirfenidone (designated as the treatment group) versus pirfenidone monotherapy (designated as the control group), we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs).
METHODS
RCTs of NAC plus pirfenidone were reviewed searching from databases and networks of unpublished and published studies in any language. Using pair-wise meta-analysis, changes in pulmonary function test (PFT) parameters and safety were evaluated.
RESULTS
Two independent reviewers selected and obtained data from 5 RCTs (n = 398), comprising 1 study from Japan, 1 from Europe, and 3 from China. NAS plus pirfenidone as compared to pirfenidone monotherapy for IPF may not reduce the incidence of skin effects(RR 1.26 [95%CI 0.64 to 2.45]) and mortality(RR 0.35 [95%CI 0.07 to 1.68])(both moderate certainty). NAS plus pirfenidone as compared to pirfenidone monotherapy for IPF may not reduce the incidence of at least one side effects(RR 1.00 [95%CI 0.84 to 1.19]; low certainty),severe side effects(RR 0.67 [95%CI 0.30 to 1.47]; low certainty) and gastrointestinal effects(RR 0.67 [95%CI 0.41 to 1.09]; low certainty) with possibly no effect in Δ%DLco(SMD -0.17 [95%CI -0.15 to 0.48]; low certainty). Meanwhile, the effect of NAS plus pirfenidone as compared to pirfenidone monotherapy on ΔFVC(SMD 0.18 [95%CI -0.68 to 1.05]), Δ%FVC(SMD -2.62 [95%CI -5.82 to 0.59]) and Δ6MWT(SMD -0.35 [95%CI -0.98 to 0.28]) is uncertain(extremely low certainty).
CONCLUSION
Moderate certainty evidence suggests that NAS plus pirfenidone, compared to pirfenidone monotherapy for IPF, does not reduce the incidence of skin effects and mortality.
Topics: Humans; Acetylcysteine; Pyridones; Treatment Outcome; Idiopathic Pulmonary Fibrosis
PubMed: 38031002
DOI: 10.1186/s12890-023-02778-w