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Objective We compared the efficacy of four treatment strategies for chronic hepatitis B (CHB): tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), tenofovir amibufenamide (TMF), and TDF-to-TAF switch strategies strategy. We conducted a network meta-analysis to provide evidence-based clinical guidance. Methods We systematically retrieved PubMed, Web of Science, Cochrane Library, Embase, and China National Knowledge Infrastructure (CNKI) databases up to April 2025 for randomized controlled trials (RCTs) and cohort studies. We assessed literature quality using the Cochrane Risk of Bias (ROB) tool and Newcastle-Ottawa Scale (NOS). Stata 17 was employed for network meta-analysis, focusing on virological response rate, hepatitis B surface antigen (HBsAg) clearance rate, hepatitis B e antigen (HBeAg) clearance rate, and alanine aminotransferase (ALT) normalization rate. Results Virological response did not differ between TMF monotherapy and TDF-to-TAF switch (OR = -0.03; 95% CI -0.42 to 0.36). HBsAg clearance was similar between TAF and TMF (95% CI: -1.17-1.14). For the rate of HBeAg loss, both TAF and TMF exhibited favorable therapeutic effects. For ALT normalization rate, TMF monotherapy was the most effective, with an average effect size of 0.11 (95% CI: -0.14-0.37), while TDF monotherapy was generally inferior to the other three treatment strategies. Conclusion Our findings may help guide the selection of individualized CHB treatment strategies. However, given the limited evidence and potential bias, these results are preliminary and must be interpreted with caution. For regimens such as TMF that lack robust data, well-established alternatives should be preferred. Long-term, multi-endpoint studies are required to confirm both efficacy and safety before routine clinical adoption.

Accurate Terminal Aerodrome Forecasts (TAFs) are essential for aviation safety and operational efficiency worldwide. This study develops an AI framework for automated TAF generation, including data preprocessing, model development, and evaluation. Using GFS and ECMWF datasets from 2020–2023 and real TAF forecasts from Brno International Airport the study explores the effectiveness of ML approaches for wind speed and visibility prediction. Principal Component Analysis (PCA) efficiently reduced dimensionality for wind speed predictors but proved less effective for visibility, highlighting its complex nature. Feature importance analysis identified initial observations and seasonal patterns as dominant predictors, underscoring the influence of data quality. Regression models for wind speed met ICAO standards. While Gradient Boosting (GB) classification outperformed human forecasts in raw accuracy, it suffered from poor probability calibration due to dataset imbalance. A critical evaluation of accuracy metrics – such as log-loss and F1-score – revealed their advantages and limitations, particularly in handling imbalanced datasets and probabilistic forecasting. Beyond its empirical findings, the study provides a theoretical foundation for integrating machine learning (ML) into TAF generation, discussing methodological considerations and the interaction between model performance and forecast interpretability. Future research is recommended to focus on the local models, explore advanced models, and expand the framework to diverse climatic conditions.

Introduction: Given the availability of a growing number of HIV treatment options, it becomes essential to have a clear understanding of the related economic-organizational evidence, to operate informed and conscious choices. The study aims to define the economic and organizational impact related to a consolidated use of Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF), within the Italian National Healthcare Service (NHS), for the treatment of both naïve and experienced HIV individuals. Materials and methods: A budget impact analysis was developed assuming the NHS perspective and considering a 36-month time horizon. Scenario A, representative of the current situation of consumption of the different therapeutic alternatives (derived from the most update guidelines), was compared with Scenario B, assuming a greater adoption of BIC/FTC/TAF. An organizational impact analysis was conducted to define any advantages for hospitals, devoted to the management of any ART-related adverse events. Results: The BIA revealed an economic saving of 0.97% (26,040,271.36 €) given a higher penetration rate for BIC/FTC/TAF, for the treatment of HIV individuals assuming ART in Italy. From an organizational perspective, a greater BIC/FTC/TAF administration would generate a reduction in the overall hospital accesses devoted to the management of adverse events, generating an overall saving of 245,938 hours, considering the time spent by the healthcare professionals involved in the care and treatment of individuals with HIV. Conclusions: BIC/FTC/TAF represent an interesting possibility for the rapid initiation of ART, as well as for switches, being able to optimize the clinical pathway of a patient with HIV, from an economic and organizational perspective.

PurposeTo determine whether changing from a tenofovir disoproxil fumarate (TDF)- to a tenofovir alafenamide fumarate (TAF)-containing regimen is correlated with weight changes in a human immunodeficiency virus (HIV)-positive adult cohort.MethodsRetrospective analysis was conducted of data gathered from routine care in a university hospital in Munich, Germany, between July 2015 and June 2017. Data from patients’ charts were extracted and a two-step approach was applied. First, weight/BMI progression within 1 year after initiation of either TDF or TAF was compared. Subsequently, weight measurements within subjects changing from a TDF- to a TAF-containing antiretroviral regimen were analyzed by means of a repeated measurements general linear model.ResultsAfter 360 days of initiating TAF, patients showed a mean (± standard deviation) percentual weight increase of 3.17 ± 0.21, whereas after 360 days of initiating TDF, patients only showed a mean (± standard deviation) percentual weight increase of 0.55 ± 0.17. The repeated measurements general linear model for within-subjects design showed a statistically significant correlation in weight after changing from a TDF to a TAF containing antiretroviral regimen. The weight difference between the two measurements while on TDF was not statistically significant, but every measure after switching to TAF was significantly higher than the previous.ConclusionChanging from a TDF- to a TAF-containing regimen is correlated with weight gain in this retrospectively analyzed real-world cohort in Munich, Germany.

HIV-1 is a chronic disease managed by strictly adhering to daily antiretroviral therapy (ART). However, not all people living with HIV-1 have access to ART, and those with access may not adhere to treatment regimens increasing viral load and disease progression. Here, a subcutaneous nanofluidic implant was used as a long-acting (LA) drug delivery platform to address these issues. The device was loaded with tenofovir alafenamide (TAF) and implanted in treatment-naïve simian HIV (SHIV)-positive nonhuman primates (NHP) for a month. We monitored intracellular tenofovir-diphosphate (TFV-DP) concentration in the target cells, peripheral blood mononuclear cells (PBMC). The concentrations of TFV-DP were maintained at a median of 391.0 fmol/106 cells (IQR, 243.0 to 509.0 fmol/106 cells) for the duration of the study. Further, we achieved drug penetration into lymphatic tissues, known for persistent HIV-1 replication. Moreover, we observed a first-phase viral load decay of −1.14 ± 0.81 log10 copies/mL (95% CI, −0.30 to −2.23 log10 copies/mL), similar to −1.08 log10 copies/mL decay observed in humans. Thus, LA TAF delivered from our nanofluidic implant had similar effects as oral TAF dosing with a lower dose, with potential as a platform for LA ART.

The urgent response to the COVID-19 pandemic required accelerated evaluation of many approved drugs as potential antiviral agents against the causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Using cell-based, biochemical, and modeling approaches, we studied the approved HIV-1 nucleoside/tide reverse transcriptase inhibitors (NRTIs) tenofovir (TFV) and emtricitabine (FTC), as well as prodrugs tenofovir alafenamide (TAF) and tenofovir disoproxilfumarate (TDF) for their antiviral effect against SARS-CoV-2. A comprehensive set of in vitro data indicates that TFV, TAF, TDF, and FTC are inactive against SARS-CoV-2. None of the NRTIs showed antiviral activity in SARS-CoV-2 infected A549-hACE2 cells or in primary normal human lung bronchial epithelial (NHBE) cells at concentrations up to 50 µM TAF, TDF, FTC, or 500 µM TFV. These results are corroborated by the low incorporation efficiency of respective NTP analogs by the SARS-CoV-2 RNA-dependent-RNA polymerase (RdRp), and lack of the RdRp inhibition. Structural modeling further demonstrated poor fitting of these NRTI active metabolites at the SARS-CoV-2 RdRp active site. Our data indicate that the HIV-1 NRTIs are unlikely direct-antivirals against SARS-CoV-2, and clinicians and researchers should exercise caution when exploring ideas of using these and other NRTIs to treat or prevent COVID-19.

Tenofovir disoproxil fumarate (TDF) seems to prevent hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV). However, the mechanism is still little known. This study aimed to investigate the the roles and mechanisms of TDF, tenofovir alafenamide fumarate (TAF), and entecavir (ETV) on the malignant characteristics of liver cancer cells. Using the wound-healing assays, transwell assays, matrigel transwell assays, and cell counting kit-8 (CCK-8) assays, it was possible to identify that TDF/TAF, inhibited migration, invasion, and proliferation of HepG2 cells and Huh7 cells. To investigate the mechanisms, we performed TOP/FOP-Flash system, Western blot, and RT-qPCR assays of liver cancer cells cultured with TDF/TAF and found a lower activity of Wnt/β-catenin signaling pathway compared with control cells. Finally, Hepatitis C virus p7 trans-regulated protein 3 (p7TP3), a tumor suppressor in liver cancers, was significantly increased in HepG2 cells and Huh7 cells that treated with TDF/TAF. However, entecavir (ETV)-treated liver cancer cells showed no significant difference in the malignant characteristics of liver cancer cells, activity of Wnt/β-catenin signaling pathway, and expression of p7TP3, compared with the control groups. To conclude, TDF/TAF maybe novel promising therapeutic strategy for liver cancers, including HCC and hepatoblastoma, via Wnt/β-catenin signaling pathway, by up-regulating expression of the tumor suppressor, p7TP3.

Long-acting (LA) HIV pre-exposure prophylaxis (PrEP) offers the potential to improve adherence by lowering the burden of daily or on-demand regimens of antiretroviral (ARV) drugs. This paper details the fabrication and in vitro performance of a subcutaneous and trocar-compatible implant for the LA delivery of tenofovir alafenamide (TAF). The reservoir-style implant comprises an extruded tube of a biodegradable polymer, poly(ε-caprolactone) (PCL), filled with a formulation of TAF and castor oil excipient. Parameters that affect the daily release rates of TAF are described, including the surface area of the implant, the thickness of the PCL tube walls (between 45 and 200 µm), and the properties of the PCL (e.g., crystallinity). In vitro studies show a linear relationship between daily release rates and surface area, demonstrating a membrane-controlled release mechanism from extruded PCL tubes. Release rates of TAF from the implant are inversely proportional to the wall thickness, with release rates between approximately 0.91 and 0.15 mg/day for 45 and 200 µm, respectively. The sustained release of TAF at 0.28 ± 0.06 mg/day over the course of 180 days in vitro was achieved. Progress in the development of this implant platform addresses the need for new biomedical approaches to the LA delivery of ARV drugs.

BackgroundThe aim of this randomized clinical trial (RCT) was to compare immunological changes in virally suppressed people living with HIV (PLWH) switching from a three-drug regimen (3DR) to a two-drug regimen (2DR).MethodsAn open-label, prospective RCT enrolling PLWH receiving a 3DR who switched to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or dolutegravir/lamivudine (DTG/3TC) was performed. Blood was taken at baseline and months 6 and 12. The primary outcome was the change in CD4+ or CD8+ T-cell counts and CD4/CD8 ratio over time points. The secondary outcomes were the changes in immunological and inflammatory parameters. Parametric mixed-linear models with random intercepts and slopes were fitted separately for each marker after controlling for potential confounders.ResultsBetween the two arms (33 PLWH each), there was no difference in CD4+ or CD8+ T cells, CD4/CD8 ratio, and IL-6 trajectories. PLWH switching to DTG/3TC had increased levels of both transitional memory and terminally differentiated CD4+ T cells (arm–time interaction p-value = 0.02) and to a lesser extent for the corresponding CD8+ T-cell subsets (p = 0.09). Significantly lower levels of non-classical monocytes were detected in the B/F/TAF arm at T6 (diff = −6.7 cells/mm3; 95% CI; −16, +2.6; p-value for interaction between arm and time = 0.03). All differences were attenuated at T12.ConclusionNo evidence for a difference in absolute CD4+ and CD8+ T-cell counts, CD4/CD8 ratio, and IL-6 trajectories by study arm over 12 months was found. PLWH on DTG/3TC showed higher levels of terminally differentiated and exhausted CD4+ and CD8+ T lymphocytes and non-classical monocytes at T6. Further studies are warranted to better understand the clinical impact of our results.Clinical Trial Registrationhttps://clinicaltrials.gov, identifier NCT04054089.

Template activating factor-I (TAF-I) is a multifunctional protein involved in various biological processes including the inhibition of histone acetylation, DNA replication, cell cycle regulation, and oncogenesis. Two main TAF-I isoforms with different N-termini, TAF-Iα and TAF-Iβ (SET), are expressed in cells. There are numerous data about functional properties of TAF-Iβ, whereas the effects of TAF-Iα remain largely unexplored. Here, we employed focus formation and cell proliferation assays, TUNEL staining, cytological analysis, and RT-qPCR to compare the effects of human TAF-Iα and TAF-Iβ genes, transiently expressed in Rat2 cells and in Misgurnus fossilis loaches. We found that both TAF-I isoforms possessed equal oncogenic potential in these systems. Furthermore, an overexpression of human TAF-Iα and TAF-Iβ in Rat2 cells promoted their proliferation. Accordingly, the mitotic index was increased in the transgenic loaches expressing human TAF-Iα or TAF-Iβ. TUNEL assay as well as downregulation of p53 gene and upregulation of bcl-2 gene in these transgenic loaches demonstrated that both isoforms suppressed apoptosis. Thus, TAF-Iα isoform exerts the same oncogenic potential as TAF-Iβ, likely by suppressing the apoptosis and promoting cell proliferation.