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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 -
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 -
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 -
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 -
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 -
Blood Advances May 2024Cytoreductive therapy is not routinely recommended for younger patients with polycythemia vera (PV) due to concern that treatment toxicity may outweigh therapeutic... (Meta-Analysis)
Meta-Analysis
Cytoreductive therapy is not routinely recommended for younger patients with polycythemia vera (PV) due to concern that treatment toxicity may outweigh therapeutic benefits. However, no systematic data support this approach. To support objective risk/benefit assessment of cytoreductive drugs in patients with PV aged <60 years (PV<60), this systematic review and meta-analysis was conducted to evaluate toxicity and disease-related complications in PV<60 treated with interferon alfa (rIFN-α) or hydroxyurea (HU). A search of PubMed, Scopus, Web of Science and Embase identified 693 unique studies with relevant keywords, of which 14 met inclusion criteria and were selected for analysis. The weighted average age of patients treated with rIFN-α was 48 years (n = 744 patients; 12 studies) and for HU was 56 years (n = 1397; 8 studies). The weighted average duration of treatment for either drug was 4.5 years. Using a Bayesian hierarchical model, the pooled annual rate of discontinuation due to toxicity was 5.2% for patients receiving rIFN-α (n = 587; 95% confidence interval [CI], 2.2-8.2) and 3.6% for HU (n = 1097; CI, 1-6.2). The average complete hematologic response for rIFN-α and HU was 62% and 52%, respectively. Patients experienced thrombotic events at a pooled annual rate of 0.79% and 1.26%; secondary myelofibrosis at 1.06% and 1.62%; acute myeloid leukemia at 0.14% and 0.26%; and death at 0.87% and 2.65%, respectively. No treatment-related deaths were reported. With acceptable rates of nonfatal toxicity, cytoreductive treatment, particularly with disease-modifying rIFN-α, may benefit PV<60. Future randomized trials prioritizing inclusion of PV<60 are needed to establish a long-term benefit of early cytoreductive treatment in these patients.
Topics: Humans; Polycythemia Vera; Treatment Outcome; Interferon-alpha; Hydroxyurea; Adult; Middle Aged; Cytoreduction Surgical Procedures; Age Factors
PubMed: 38507746
DOI: 10.1182/bloodadvances.2023012459 -
Journal of the International AIDS... Mar 2024Disengagement from antiretroviral therapy (ART) care is an important reason why people living with HIV do not achieve viral load suppression become unwell.
INTRODUCTION
Disengagement from antiretroviral therapy (ART) care is an important reason why people living with HIV do not achieve viral load suppression become unwell.
METHODS
We searched two databases and conference abstracts from January 2015 to December 2022 for studies which reported reasons for disengagement from ART care. We included quantitative (mainly surveys) and qualitative (in-depth interviews or focus groups) studies conducted after "treat all" or "Option B+" policy adoption. We used an inductive approach to categorize reasons: we report how often reasons were reported in studies and developed a conceptual framework for reasons.
RESULTS
We identified 21 studies which reported reasons for disengaging from ART care in the "Treat All" era, mostly in African countries: six studies in the general population of persons living with HIV, nine in pregnant or postpartum women and six in selected populations (one each in people who use drugs, isolated indigenous communities, men, women, adolescents and men who have sex with men). Reasons reported were: side effects or other antiretroviral tablet issues (15 studies); lack of perceived benefit of ART (13 studies); psychological, mental health or drug use (13 studies); concerns about stigma or confidentiality (14 studies); lack of social or family support (12 studies); socio-economic reasons (16 studies); health facility-related reasons (11 studies); and acute proximal events such as unexpected mobility (12 studies). The most common reasons for disengagement were unexpected events, socio-economic reasons, ART side effects or lack of perceived benefit of ART. Conceptually, studies described underlying vulnerability factors (individual, interpersonal, structural and healthcare) but that often unexpected proximal events (e.g. unanticipated mobility) acted as the trigger for disengagement to occur.
DISCUSSION
People disengage from ART care for individual, interpersonal, structural and healthcare reasons, and these reasons overlap and interact with each other. While HIV programmes cannot predict and address all events that may lead to disengagement, an approach that recognizes that such shocks will happen could help.
CONCLUSIONS
Health services should focus on ways to encourage clients to engage with care by making ART services welcoming, person-centred and more flexible alongside offering adherence interventions, such as counselling and peer support.
Topics: Adolescent; Female; Humans; Male; Pregnancy; Anti-Retroviral Agents; Developing Countries; HIV Infections; Sexual and Gender Minorities; Medication Adherence; Patient Dropouts
PubMed: 38494657
DOI: 10.1002/jia2.26230 -
Canadian Journal of Gastroenterology &... 2024People living with hepatitis C infection (HCV) have a significant impact on the global healthcare system, with high rates of inpatient service use. Direct-acting... (Review)
Review
BACKGROUND
People living with hepatitis C infection (HCV) have a significant impact on the global healthcare system, with high rates of inpatient service use. Direct-acting antivirals (DAAs) have the potential to alleviate this burden; however, the evidence on the impact of HCV infection and hospital outcomes is undetermined. This systematic review aims to assess this research gap, including how DAAs may modify the relationship between HCV infection and hospital-related outcomes.
METHODS
We searched five databases up to August 2022 to identify relevant studies evaluating the impact of HCV infection on hospital-related outcomes. We created an electronic database of potentially eligible articles, removed duplicates, and then independently screened titles, abstracts, and full-text articles.
RESULTS
A total of 57 studies were included. Analysis of the included studies found an association between HCV infection and increased number of hospitalizations, length of stay, and readmissions. There was less consistent evidence of a relationship between HCV and in-hospital mortality. Only four studies examined the impact of DAAs, which showed that DAAs were associated with a reduction in hospitalizations and mortality. In the 14 studies available among people living with HIV, HCV coinfection similarly increased hospitalization, but there was less evidence for the other hospital-related outcomes.
CONCLUSIONS
There is good to high-quality evidence that HCV negatively impacts hospital-related outcomes, primarily through increased hospitalizations, length of stay, and readmissions. Given the paucity of studies on the effect of DAAs on hospital outcomes, future research is needed to understand their impact on hospital-related outcomes.
Topics: Humans; Antiviral Agents; Hepacivirus; Hepatitis C, Chronic; Hepatitis C; Hospitals
PubMed: 38487594
DOI: 10.1155/2024/3325609