Risk of dyslipidaemia in people living with HIV who are taking tenofovir alafenamide: a systematic review and meta-analysis.

INTRODUCTION: Among many antiretroviral drugs, tenofovir alafenamide is used extensively in combination regimens of tenofovir/emtricitabine or tenofovir/emtricitabine/bictegravir. However, concerns have arisen about the potential of tenofovir alafenamide to exacerbate hyperlipidaemia. This meta-analysis evaluates the relationship between tenofovir alafenamide use and lipid-profile alterations in people living with HIV. METHODS: We searched PubMed, Ovid MEDLINE, EMBASE and the Cochrane Library to identify studies on changes in cholesterol levels (e.g. total cholesterol, low-density and high-density lipoprotein cholesterol, and triglycerides) in people living with HIV who received treatment with a regimen containing tenofovir alafenamide (data collected 31 March 2023, review completed 30 July 2023). Potential risk factors for worsening lipid profile during treatment with tenofovir alafenamide were also evaluated. RESULTS: Sixty-five studies involving 39,713 people living with HIV were selected. Significant increases in total cholesterol, low-density and high-density lipoprotein cholesterol, and triglycerides were observed after treatment with tenofovir alafenamide. Specifically, low-density lipoprotein cholesterol (+12.31 mg/dl) and total cholesterol (+18.86 mg/dl) increased markedly from the third month of tenofovir alafenamide use, with significant elevations observed across all time points up to 36 months. Comparatively, tenofovir alafenamide regimens resulted in higher lipid levels than tenofovir disoproxil fumarate regimens at 12 months of use. Notably, discontinuation of the tenofovir alafenamide regimen led to significant decreases in low-density lipoprotein cholesterol (-9.31 mg/dl) and total cholesterol (-8.91 mg/dl). Additionally, tenofovir alafenamide use was associated with increased bodyweight (+1.38 kg; 95% confidence interval: 0.92-1.84), which became more pronounced over time. Meta-regression analysis identified young age, male sex and low body mass index as risk factors for worsening cholesterol levels in individuals treated with tenofovir alafenamide. CONCLUSIONS: Tenofovir alafenamide use in people living with HIV is associated with significant alterations in lipid profile.

Role of tenofovir dipivoxil in gut microbiota recovery from HBV-infection induced dysbiosis.

BACKGROUND: Studies have found dysbiosis of the gut microbiota in individuals infected with the hepatitis B virus (HBV). Tenofovir dipivoxil (TDF) is one of the preferred oral antiviral drugs used for the treatment of chronic hepatitis B (CHB), but the extent to which TDF is able to affect the gut microbiota and inflammatory factors of a patient remains largely unexplored. In this study, we collected stool samples from HBV patients prior to medication and from CHB patients treated with TDF. RESULTS: The gut microbiota and inflammatory factors were assessed in 42 healthy subjects (HC group), 109 HBV-infected subjects, including 48 CHB patients who were not medicated with nucleoside analogue drugs (No-NAs group), and 61 CHB patients who were medicated with TDF (TDF group). 16 S rRNA sequencing revealed that TDF treatment caused significant changes in the gut microbiota of HBV-infected individuals; however, the gut microbiota of HBV-infected individuals did not fully recover to a pre-dysbiosis state. The relative abundance of Bacteroidota gradually decreased from the HC group to the No-NAs and TDF groups. The relative abundance of Fusobacteriota was significantly higher in the No-NAs group than in the HC group. At the genus level, Dialister, Eubacterium_hallii_group, Halomonas, Collinsella, Sphingomonas, Xanthomonadaceae_unclassified, and Rhizobiaceae_unclassified were overrepresented; while the abundance of Bacteroides and Fusobacterium decreased significantly in the No-NAs and TDF groups. CONCLUSIONS: This study showed that TDF treatment significantly improved the regulation of the gut microbiota and aided in dysbiosis recovery. We did not observe significant improvement in serum inflammatory factor concentrations, which may be related to the relatively short duration of TDF administration in this study.

Preparation of tenofovir amibufenamide fumarate spherical particles to improve tableting performance and sticking propensity by designing a spherical crystallization process.

Tenofovir amibufenamide fumarate (TMF) is the first oral drug developed in Asia for the treatment of adult patients with chronic viral hepatitis B, however, further applications are limited by poor tableting performance and high sticking propensity. In this work, the spherulitic growth process of TMF has been designed and explored with the help of molecular dynamics simulation and process analysis technologies (ATR-FTIR, FBRM and EasyViewer). The spherical particles with high bulk density, good flowability and uniform particle size distribution are prepared by a simple quenching process. More importantly, experimental results show that spherical particles have higher average tensile strength (100.8% increase), higher plastic deformability and lower amount of punch sticking (87.4% decrease in 30 tablets) compared to the commercial powder products. These contributions not only shed light on the design principle of drug spherulitic growth processes, but also provide guidance for the manufacture of high-quality tablet products.

Tenofovir versus entecavir on long-term prognosis in hepatocellular carcinoma patients with concurrent metabolic dysfunction-associated steatotic liver disease and hepatitis B.

BACKGROUND: Currently, there remains ongoing controversy about the selection of postoperative antiviral drugs for hepatocellular carcinoma (HCC) patients with concurrent metabolic dysfunction-associated steatotic liver disease (MASLD) and hepatitis B virus (HBV) infection (HPMH) who underwent hepatectomy. METHOD: A multivariate Cox proportional hazards model and a propensity score matching (PSM) analysis were implemented to ensure equal baseline characteristics. The Kaplan‒Meier survival curves were employed for prognosis comparison between the two groups. RESULTS: This study included 225 HPMH who all received post-hepatectomy antiviral therapy; with 107 in the tenofovir disoproxil fumarate (TDF) group and 118 in the entecavir (ETV) group. In the entire cohort, according to the multivariate analysis, patients in the TDF group showed better recurrence-free survival (RFS) (HR = 0.78; 95% CI, 0.55-0.95; p = 0.030) and overall survival (OS) (HR = 0.52; 95% CI, 0.30-0.97; p = 0.021) than those in the ETV group. After executing a PSM analysis, Kaplan‒Meier survival curve analysis disclosed significant differences for both RFS and OS between the two groups (p = 0.03 and p = 0.01, respectively). CONCLUSIONS: In summary, our study suggests a more significant association of TDF in improving RFS and OS than ETV in HPMH who underwent hepatectomy through multivariate and PSM analysis. These findings indicate that the choice of antiviral drugs in HPHM holds crucial significance in guiding patient long-term prognosis.

Prospective Analysis of Safety and Efficacy of Tenofovir Alafenamide Fumarate (TAF) in European Real-World Patients with Chronic Hepatitis B: A Single-Centre Real-Word Cohort Study.

Background: Tenofovir alafenamide (TAF) is a novel prodrug of tenofovir for the treatment of chronic hepatitis B (CHB) that has shown a favourable renal safety profile while offering suppression of HBV DNA similar to tenofovir disoproxil fumarate (TDF). We aimed to study changes in markers of HBV replication and renal function in a real-world setting in European patients. Methods: In our prospective single-arm, non-interventional observational study, HBeAg-positive and HBeAg-negative patients with chronic HBV mono-infection receiving TAF as their first or following line treatment were enrolled. HBV DNA, HBsAg, markers of bone metabolism, and renal function were determined at baseline and every consecutive 3 months. Results: A total of 50 patients (70% male) were included. The mean duration of TAF treatment was 18 (3-36) months. In 20 patients with detectable HBV DNA at baseline, median serum levels of HBV DNA log10 changed from 2.33 (0.766-6.47) to 1.04 IU/mL at the end of observation and became undetectable in 11 patients. Median HBsAg log10 decreased from 3.37 (0.88-5.10) to 2.39 (1.52-4.19) IU/mL. During the entire observation period, the renal function parameters remained stable in patients with normal renal function and even in those with renal dysfunction. Mild adverse events were reported by 14 patients (28%). Conclusions: TAF was a safe and effective treatment, also in patients with decreased renal function.

Effects of tenofovir alafenamide fumarate on serum lipid profiles in patients with chronic hepatitis B.

BACKGROUND: Concerns have been raised regarding changes in lipid profiles among patients with chronic hepatitis B (CHB) during tenofovir alafenamide fumarate (TAF) treatment. We aimed to evaluate the effect of TAF treatment on the lipid profiles of patients with CHB. METHODS: A total of 430 patients with CHB from three hospitals were retrospectively included, including 158 patients treated with TAF and 272 patients treated with tenofovir disoproxil fumarate (TDF). RESULTS: In this multicenter cohort, the cumulative incidence of dyslipidemia was notably higher in the TAF group than in the TDF group (P < 0.001). After TAF treatment, a significant elevation was observed in triglyceride (TG) levels (from 0.83 mmol/L to 1.02 mmol/L, P < 0.001) and total cholesterol (TC) levels (from 4.16 mmol/L to 4.32 mmol/L, P < 0.001). Similar changes in TG and TC levels were observed in the TAF group after propensity score matching (PSM). The TG levels (from 0.83 mmol/L to 1.04 mmol/L, P < 0.001) and TC levels (from 4.16 mmol/L to 4.38 mmol/L, P < 0.001) were both increased significantly compared to the baseline levels in the PSM cohort of patients treated with TAF. TAF treatment was independently associated with elevated TG levels (HR = 2.800, 95% CI: 1.334-5.876, P = 0.006) and TC levels (HR = 9.045, 95% CI: 3.836-21.328, P < 0.001). CONCLUSIONS: Compared with TDF treatment, TAF treatment was associated with dyslipidemia in patients with CHB. Close monitoring of lipid profiles is needed in patients with CHB who received TAF treatment.

Comparative efficacy and safety of tenofovir amibufenamide vs tenofovir alafenamide in the initial 48-week treatment of high viral load chronic hepatitis B: A single-centre retrospective study.

BACKGROUND/AIM: Tenofovir amibufenamide (TMF) employs innovative ProTide technology and a methylation strategy to enhance the lipid solubility and plasma stability of the amide bond, providing advantages over tenofovir alafenamide (TAF). Despite promising Phase III clinical trial results demonstrating its antiviral efficacy, real-world data on TMF remains scarce. This study evaluates the antiviral efficacy and safety of TMF compared to TAF as the initial treatment in patients with high viral loads of chronic hepatitis B (CHB). METHODS: We retrospectively collected clinical data from March 1 2022 to June 30 2022 for highly viremic CHB patients who received either TMF (n = 58) or TAF (n = 32) as their initial monotherapy at Beijing YouAn Hospital. To understand the efficacy and safety of TMF over 48 weeks, we compared the virological response rates and HBeAg/HBsAg serological clearance rates between TMF and TAF groups. Also, the changes in serum creatinine, eGFR and serum lipid levels were assessed. RESULTS: Baseline median HBV DNA levels were 7.85 (6.89, 8.36) IgIU/ml for TMF and 7.44 (6.89, 8.03) IgIU/ml for TAF. Median ALT levels were 102.0 (56.0, 210.0) U/L for TMF and 195.0 (73.5, 371.0) U/L for TAF, with HBeAg positivity rates of 70.7% and 75.0%, respectively. At 48 weeks, virological response rates (HBV DNA <10 IU/ml) were 43.5% (20/46) for TMF and 42.9% (12/28) for TAF (p = 1.000). ALT normalization rates were 87.9% for TMF and 90.6% for TAF (p = .969), and HBeAg serological clearance rates were 21.1% and 18.2%, respectively (p = 1.000). No patients achieved HBsAg clearance. Compared with the baseline, LDL-C levels increased, while eGFR decreased, with no significant differences in serum creatinine, triglycerides and total cholesterol levels noted at week 48 for both TMF and TAF groups. CONCLUSION: TMF demonstrates comparable antiviral efficacy to TAF when used as initial therapy in highly viremic CHB patients, with similar impacts on renal function and lipid profiles.

Tenofovir versus entecavir on the prognosis of hepatitis B virus-related hepatocellular carcinoma: a reconstructed individual patient data meta-analysis.

Background: Hepatitis B, often leading to Hepatocellular carcinoma (HCC), poses a major global health challenge. While Tenofovir (TDF) and Entecavir (ETV) are potent treatments, their comparative effectiveness in improving recurrence-free survival (RFS) and overall survival (OS) rates in HBV-related HCC is not well-established. Methods: We conducted an individual patient data meta-analysis using survival data from randomized trials and high-quality propensity score-matched studies to compare the impact of Tenofovir (TDF) and Entecavir (ETV) on RFS and OS in HBV-related HCC patients. Data from six databases and gray literature up to 30 August 2023, were analyzed, utilizing Kaplan-Meier curves, stratified Cox models, and shared frailty models for survival rate assessment and to address between-study heterogeneity. The study employed restricted mean survival time analysis to evaluate differences in RFS and OS between TDF-treated and ETV-treated patients. Additionally, landmark analyses compared early (<2 years) and late (≥2 years) tumor recurrence in these cohorts. Results: This study incorporated seven research articles, covering 4,602 patients with HBV-related HCC (2,082 on TDF and 2,520 on ETV). Within the overall cohort, TDF recipients demonstrated significantly higher RFS (p = 0.042) and OS (p < 0.001) than those on ETV. The stratified Cox model revealed significantly improved OS for the TDF group compared to the ETV group (hazard ratio, 0.756; 95% confidence interval, 0.639-0.896; p = 0.001), a result corroborated by the shared frailty model. Over a follow-up period of 1-8 years, no significant difference was noted in the mean time to death between the TDF and ETV groups. The rates of early recurrence did not significantly differ between the groups (p = 0.735). However, TDF treatment was significantly associated with a reduced risk of late recurrence compared to ETV (p < 0.001). In the HCC resection subgroup, the disparities in OS, early, and late recurrence rates between the two treatments paralleled those seen in the overall cohort. Conclusion: Compared to ETV, TDF may enhance OS and reduce late tumor recurrence risk in HBV-related HCC patients receiving curative treatment. However, there was no statistically significant distinction in the timing of tumor recurrence and mortality between patients administered TDF and those prescribed ETV. Systematic Review Registration: http://www.crd.york.ac.uk/prospero/.

Lipid and glucose profiles in pregnant women with HIV on tenofovir-based antiretroviral therapy.

OBJECTIVE: Tenofovir alafenamide (TAF)-based antiretroviral therapy (ART) regimens have been associated with adverse changes in lipid and glucose profiles compared with tenofovir disoproxil fumarate (TDF)-based ART, but data in pregnancy is limited. We evaluated metabolic markers in pregnant women with HIV after starting TAF- vs TDF-based ART. METHODS: We analyzed data within the IMPAACT 2010/VESTED trial, which demonstrated better pregnancy outcomes in pregnant women randomized to initiate TAF/Emtricitabine/Dolutegravir (TAF/FTC+DTG; n=217) or TDF/FTC+DTG (n=215). We measured non-fasting plasma concentrations of glucose, total-cholesterol, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), lipoprotein (a), and triglycerides from samples collected eight weeks after enrollment. We employed linear regression models to estimate by-arm mean differences. RESULTS: 219 participants enrolled in the DTG arms in Zimbabwe and Uganda: 109 in the TAF/FTC+DTG and 110 in the TDF/FTC+DTG arms. At study entry, mean gestational age was 22.6 weeks, median HIV-1 RNA was 711 copies/mL, and mean age was 25.8 years. By eight weeks, mean total cholesterol was 12 mg/dL higher in women randomized to TAF/FTC+DTG versus TDF/FTC+DTG (95% CI 3.8, 21.1). Pregnant women in the TAF/FTC+DTG arm had higher mean LDL-C (7.1 mg/dL, 95% CI 0.2, 14.0), triglycerides (12.3 mg/dL, 95% CI 1.8, 22.7), lipoprotein (a) (7.3 mg/dL, 95% CI 1.1, 13.6), and lower mean HDL-C (2.8 mg/dL, 95% CI 0.1, 5.6) compared to the TDF/FTC+DTG arm. CONCLUSION: Pregnant women randomized to start TAF/FTC+DTG had higher lipids than those randomized to TDF/FTC+DTG within eight weeks of ART initiation. However, lipid levels were within normal reference ranges.

Integrated PrEP and STI Services for Transgender Women in Uganda: Qualitative Findings from a Randomized Trial.

Tenofovir alafenamide fumarate (F/TAF) pre-exposure prophylaxis (PrEP) is understudied in sub-Saharan Africa. The Tandika PrEP study was a randomized trial that evaluated same-day F/TAF initiation, the impact of drug-level feedback on PrEP adherence, and integrated PrEP and sexually transmitted infection (STI) services for HIV-negative transgender women (TGW) in Uganda (NCT04491422). From April 2022-February 2023, a qualitative sub-study of 30 in-depth interviews explored (1) perspectives on same-day initiation of F/TAF PrEP, (2) experiences of urine tenofovir testing and drug-level feedback, and (3) descriptions of self-collection of samples for STI testing. Qualitative data were analyzed using an inductive content analytic approach. Integrated PrEP/STI services were valued by TGW because the convenience of urine testing motivated adherence and allowed for tenofovir and STI detection. (1) Preferred characteristics: F/TAF-based PrEP was easy to take and not readily identifiable as an HIV-related medication, resulting in less stigma than the better-known tenofovir disoproxil fumarate (F/TDF). Weight gain associated with F/TAF use was viewed positively by TGW as a symbol of health and prosperity in African settings. (2) Adherence motivation: PrEP adherence was motivated by a desire not to disappoint healthcare workers; TGW reciprocated adherence support and drug-level feedback by taking PrEP. (3) Facilitating adherence and STI care: Urine testing enhanced STI detection and treatment. Utilization of urine for tenofovir and STI testing motivated the uptake of HIV/STI care, emphasizing the importance of integrated PrEP and STI services. Integrating PrEP/STI services into differentiated delivery models could increase prevention uptake in this vulnerable population.

A systematic review and meta-analysis comparing the impact of tenofovir and entecavir on the prognosis of hepatitis B virus-related hepatocellular carcinoma patients undergoing liver resection.

Background: Tenofovir (TDF) and entecavir (ETV) are highly effective and well-tolerated nucleos(t)ide analogs commonly prescribed for hepatitis B virus (HBV) treatment. Yet, it is unclear whether survival outcomes differ for HBV-related hepatocellular carcinoma (HCC) patients treated with ETV and TDF. Thus, this meta-analysis aimed to compare the prognostic effectiveness of ETV and TDF in HBV-related HCC patients. Methods: We comprehensively searched four databases, PubMed, Web of Science, Embase, and the Cochrane Library, to identify pertinent studies utilizing keywords "entecavir," "tenofovir," "hepatocellular carcinoma," and "liver resection." Our primary outcomes of interest encompassed overall survival (OS), recurrence-free survival (RFS), early recurrence, and late recurrence. The statistical effect size for these measures was expressed in terms of hazard ratios (HRs). Results: Our search yielded 10 studies encompassing 11 datasets involving 7,400 patients. Our meta-analysis revealed that patients treated with TDF achieved better OS (HR = 0.53; 95% confidence interval [CI] = 0.40-0.70, p < 0.0001), RFS (HR = 0.68; 95% CI = 0.57-0.80; p < 0.0001), early recurrence (HR = 0.80; 95% CI = 0.67-0.94; p < 0.0077), and late recurrence (HR = 0.64; 95% CI = 0.43-0.97; p = 0.0368). We detected publication bias potentially affecting OS but not RFS. Conclusion: Our findings demonstrated that TDF outperformed ETV regarding RFS for HBV-related HCC patients. However, to bolster the evidence and establish more conclusive conclusions, further validation via extensive and high-quality randomized controlled trials is essential. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#recordDetails, identifier CRD 42024542579.

Comparing pill counts and patient self-reports versus DBS tenofovir concentrations as ART adherence measurements with virologic outcomes and HIV drug resistance in a cohort of adolescents and young adults failing ART in Harare, Zimbabwe.

BACKGROUND: Monitoring adherence presents a challenge in adolescents and it is prudent to explore several options for determining their level of adherence. This study sought to determine ART adherence levels in adolescents and young adults (on a tenofovir-containing regimen) failing ART as measured by self-reports, pill counts and DBS tenofovir concentrations and to compare levels of agreement among the methods and determine the ability of each method to predict virological suppression. METHODS: This was a cohort study involving 107 adolescents and young adults between 10 and 24 years failing ART with viral load > 400copies/ml at enrolment. Pill count (PC) records, self-reports (SR) and DBS tenofovir concentrations (done by liquid Chromatography with tandem mass spectrometry (LC-MS/MS)) were used to determine adherence in adolescent participants failing ART in Harare. The latter was used as the reference method with a cut-off of 64 ng/ml. Determination of DBS tenofovir concentrations was also performed to rule out inadequate viral response due to low cumulative drug exposure despite high adherence (≥90 %). Longitudinal analysis was performed to determine the correlation of viral loads (VL) with adherence. The Kappa (k) coefficient was used to evaluate the level of agreement among the 3 methods. RESULTS: Poor level of agreement was found between PC records and DBS tenofovir concentrations (k = -0.115). Moderate agreement was found between DBS and SR methods (k = 0.0557). Slight agreement was found between PC and SR methods (k = 0.0078). Adherence was dependent on age at HIV diagnosis (p = 0.0184) and ART initiation (p = 0.0265). Participants who were adherent were six times more likely to be suppressed at end point than their non-adherent counterparts (OR=5.7 CI 2.1 - 16.5, p < 0.0001). CONCLUSIONS: Self-reported measure of adherence and pill counts exhibited poor agreement with the reference method used i.e. DBS tenofovir concentrations and are thus not effective methods of predicting virological suppression. TRIAL IDENTIFICATION: Participants in the present study were a subset of those in the PESU intervention ClinicalTrials.gov Identifier: NCT02833441.

Functional cure induced by tenofovir alafenamide plus peginterferon-alpha-2b in young children with chronic hepatitis B: a case series study.

BACKGROUND AND AIMS: Data on the safety and effectiveness of tenofovir alafenamide (TAF) plus peginterferon-alpha (Peg-IFN-α) in children with chronic hepatitis B (CHB) are lacking. The current study aimed to present the characteristics of four pediatric CHB patients who obtained a functional cure by using TAF and Peg-IFN-α. METHODS: In this case series study initiated in May 2019, ten children who had no clinical symptoms or signs received response-guided (HBV DNA undetectable, hepatitis B e antigen [HBeAg] loss or seroconversion, and hepatitis B surface antigen [HBsAg] loss or seroconversion) and functional cure-targeted (HBsAg loss or seroconversion) TAF (25 mg/d, orally) plus Peg-IFN-α-2b (180 µg/1.73m2, subcutaneously, once weekly) in combination (9/10) or sequential (1/10) therapy. The safety and effectiveness of these treatments were monitored. RESULTS: As of April 2024, four out of ten children obtained a functional cure after a mean of 31.5 months of treatment, and the other six children are still undergoing treatment. These four cured children, aged 2, 4, 8, and 6 years, were all HBeAg-positive and had alanine aminotransferase levels of 80, 47, 114, and 40 U/L; HBV DNA levels of 71200000, 93000000, 8220, and 96700000 IU/mL; and HBsAg levels of 39442.8, 15431.2, 22, and 33013.1 IU/mL, respectively. During treatment, all the children (10/10) experienced mild or moderate adverse events, including flu-like symptoms, anorexia, fatigue, and cytopenia. Notably, growth retardation (8/10) was the most significant adverse event; and it occurred in three cured children (3/4) treated with combination therapy and was present to a low degree in the other cured child (1/4) treated with sequential therapy. Fortunately, all three cured children recovered to or exceeded the normal growth levels at 9 months posttreatment. CONCLUSIONS: TAF plus Peg-IFN-α-2b therapy is potentially safe and effective for pediatric CHB patients, which may provide important insights for future clinical practice and study designs targeting functional cures for children with CHB.

Metabolic, Mitochondrial, and Inflammatory Effects of Efavirenz, Emtricitabine, and Tenofovir Disoproxil Fumarate in Asymptomatic Antiretroviral-Naïve People with HIV.

This study aimed to comprehensively assess the metabolic, mitochondrial, and inflammatory effects of first-line efavirenz, emtricitabine, and tenofovir disoproxil fumarate (EFV/FTC/TDF) single-tablet regimen (STR) relative to untreated asymptomatic HIV infection. To this end, we analyzed 29 people with HIV (PWH) treated for at least one year with this regimen vs. 33 antiretroviral-naïve PWH. Excellent therapeutic activity was accompanied by significant alterations in metabolic parameters. The treatment group showed increased plasmatic levels of glucose, total cholesterol and its fractions (LDL and HDL), triglycerides, and hepatic enzymes (GGT, ALP); conversely, bilirubin levels (total and indirect fraction) decreased in the treated cohort. Mitochondrial performance was preserved overall and treatment administration even promoted the recovery of mitochondrial DNA (mtDNA) content depleted by the virus, although this was not accompanied by the recovery in some of their encoded proteins (since cytochrome c oxidase II was significantly decreased). Inflammatory profile (TNFα, IL-6), ameliorated after treatment in accordance with viral reduction and the recovery of TNFα levels correlated to mtDNA cell restoration. Thus, although this regimen causes subclinical metabolic alterations, its antiviral and anti-inflammatory properties may be associated with partial improvement in mitochondrial function.

Safety of Tenofovir Disoproxil Fumarate Among Breastfeeding Infants of Patients With Chronic Hepatitis B: A Systematic Review.

An integral component to achieving worldwide chronic hepatitis B (CHB) elimination is addressing vertical transmission. Guidelines differ in their recommendations for breastfeeding while on tenofovir disoproxil fumarate (TDF). To conduct a systematic review of published studies analysing the concentration of tenofovir (TFV) in the breast milk of mothers receiving TDF and determining infant exposure from breastfeeding. We conducted a systematic literature search of studies evaluating infant safety from the breast milk of breastfeeding mothers receiving TDF for any indication that reported a TFV breast milk concentration. Daily infant exposure was used to calculate the relative dose of TFV in infants. Other pertinent information collected was the concentration of TFV in maternal and infant plasma, the duration of therapy of TDF and the indication for TDF. We identified 10 studies including 443 patients-266 of whom were mothers, and the remaining were infants-that reported the TFV concentration of breast milk in breastfeeding mothers receiving TDF. A total of 654 breast milk samples were included. The mean TFV concentration from all the studies that reported a median concentration of TFV was 4.8 ng/mL (95% CI [3.8, 5.8]). The mean infant exposure of TFV from breast milk was 0.56 µg/kg/day (95% CI [0.44, 0.68]). The mean relative dose was determined to be 0.01% of the weight-based recommended infant dose. Infant plasma levels of TFV were also collected. This was undetectable in a majority of the studies that reported it. Based on the negligible infant exposure of TFV while breastfeeding, from a pharmacologic and toxicity standpoint, maternal dosing of TDF appears safe for breastfeeding infants.

Comparative evaluation of adverse drug reactions for tenofovir alafenamide and tenofovir disoproxil fumarate using the FAERS Database: a disproportionality analysis.

BACKGROUND: Tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) are widely used nucleoside reverse transcriptase inhibitors (NRTIs), necessitating a thorough understanding of their safety profiles to ensure optimal patient care and treatment adherence. METHODS: We employed statistical methods including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS) to compare and evaluate the safety profiles of these NRTIs. RESULTS: TAF was significantly associated with weight increase (ROR: 6.43; 95% CI: 5.93-6.96) and specific psychiatric disorders. TDF showed a notable signal for renal disorders and product-related issues, including product dose omission (ROR: 3.53; 95% CI: 3.22-3.87). Additionally, the study highlighted differences in safety signals related to pregnancy outcomes, with TAF having a higher ROR for maternal exposure (ROR: 7.83; 95% CI: 7.06-8.69) and TDF for fetal exposure (ROR: 4.51; 95% CI: 3.93-5.18), underscoring the need for cautious use in pregnant women. The comparative analysis also identified signals for osteonecrosis (ROR: 108.81; 95% CI: 106.25-111.43) and bone loss (ROR: 714; 95% CI: 685.49-743.68) for TAF and TDF, respectively, highlighting the importance of bone health considerations in treatment plans. CONCLUSION: These findings underscore the importance of personalized antiviral therapy and patient safety.

Coformulated Bictegravir/Emtricitabine/Tenofovir Alafenamide for Postexposure Prophylaxis After Sexual Assault: A Retrospective Real-World Study.

We report the experience of bictegravir/emtricitabine/tenofovir alafenamide for nonoccupational postexposure prophylaxis in sexual assault cases. Between June 2021 and October 2023, 39 individuals completed the 28-day follow-up; 41% experienced some side effects, and 1 person discontinued the drug because of a rash. No individuals seroconverted to HIV during the follow-up period.

Short-Term Efficacy of Tenofovir Alafenamide in Acute-On-Chronic Liver Failure: A Single Center Experience.

Background: Patients with acute-on-chronic liver failure (ACLF) who take entecavir (ETV) and tenofovir disoproxil fumarate (TDF) experience a reduction in hepatic events and mortality. The effectiveness of tenofovir alafenamide (TAF) was not well investigated. This study was aim to compare the antiviral efficacy and mortality between TAF and ETV in patients with ACLF caused by the hepatitis B virus (HBV). Methods: One hundred and six patients with HBV-ACLF who received TAF (25 mg/day) and ETV (0.5 mg/day) for 12 weeks were analyzed. The primary endpoints were overall mortality and liver transplantation (LT) at week 12. Biochemical responses, virologic responses, mortality, drug safety, and side effects were evaluated. Results: At 4 and 12 weeks of TAF treatment, patients showed significantly higher HBV-DNA reduction (P < .001), higher HBV-DNA undetectability rates (P < .001), and lower HBV DNA levels (P < .001) in serum. Lower Child-Turcotte-Pugh (CTP) scores (P = .003) were observed at 4 weeks in the TAF group, although the CTP scores showed no difference between TAF group and ETV group at 12 weeks (P = 1.143). Lower alanine aminotransferase (ALT) levels of patients in the TAF group at week 4 and 12 were observed (P = .023 and P < .0001, separately). The mortality of TAF group was lower after 4 weeks of treatment (P = .038); however, the 2 groups had similar mortality rates at week 8 and 12. Among the causes of death in HBV-ACLF patients, we found the same incidence of liver-related problems in both groups (P > .05). Conclusions: This study showed that ACLF patients with chronic HBV infection treated with TAF had a rapid decline in HBV DNA, a higher rate of ALT reduction and improved CTP scores compared to the ETV group, thereby improving patient survival.

Antiretroviral therapy adherence among peripartum women with HIV in Kenya: an explanatory mixed methods study using dry blood spot measures and narrative interviews.

ABSTRACTAdherence to antiretroviral therapy (ART) remains sub-optimal among pregnant and postpartum women with HIV (PPWH) in high HIV prevalence low resource settings with few effective behavioral interventions. A large body of qualitative literature has established general barriers and facilitators to ART adherence in PPWH at various levels (individual, interpersonal, structural). However, research exploring the underlying behavioral mechanisms of ART adherence in PPWH with objectively verified adherence biomarkers is extremely limited. We conducted 24 in-depth interviews with postpartum women in western Kenya who had linked ART drug concentrations obtained from three dried blood spot samples across the peripartum period. Among PPWH with a low drug concentration (n = 13) compared to those with continuously high drug concentrations (n = 11), distinct themes emerged related to HIV status disclosure, social support, interactions with the health system, and health beliefs. By combining ART biomarkers with patient reported challenges, there is the potential for real-time interventions to support sustained ART adherence among PPWH and improve maternal and infant health outcomes.

Improvement of hepatic fibrosis after tenofovir disoproxil fumarate switching to tenofovir alafenamide for three years.

BACKGROUND: Both tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) are the first-line treatments for chronic hepatitis B (CHB). We have showed switching from TDF to TAF for 96 weeks resulted in further alanine aminotransferase (ALT) improvement, but data remain lacking on the long-term benefits of TDF switching to TAF on hepatic fibrosis. AIM: To assess the benefits of TDF switching to TAF for 3 years on ALT, aspartate aminotransferase (AST), and hepatic fibrosis improvement in patients with CHB. METHODS: A single center retrospective study on 53 patients with CHB who were initially treated with TDF, then switched to TAF to determine dynamic patterns of ALT, AST, AST to platelet ratio index (APRI), fibrosis-4 (FIB-4) scores, and shear wave elastography (SWE) reading improvement at switching week 144, and the associated factors. RESULTS: The mean age was 55 (28-80); 45.3%, males; 15.1%, clinical cirrhosis; mean baseline ALT, 24.8; AST, 25.7 U/L; APRI, 0.37; and FIB-4, 1.66. After 144 weeks TDF switching to TAF, mean ALT and AST were reduced to 19.7 and 21, respectively. From baseline to switching week 144, the rates of ALT and AST < 35 (male)/25 (female) and < 30 (male)/19 (female) were persistently increased; hepatic fibrosis was also improved by APRI < 0.5, from 79.2% to 96.2%; FIB-4 < 1.45, from 52.8% to 58.5%, respectively; mean APRI was reduced to 0.27; FIB-4, to 1.38; and mean SWE reading, from 7.05 to 6.30 kPa after a mean of 109 weeks switching. The renal function was stable and the frequency of patients with glomerular filtration rate > 60 mL/min was increased from 86.5% at baseline to 88.2% at switching week 144. CONCLUSION: Our data confirmed that switching from TDF to TAF for 3 years results in not only persistent ALT/AST improvement, but also hepatic fibrosis improvement by APRI, FIB-4 scores, as well as SWE reading, the important clinical benefits of long-term hepatitis B virus antiviral treatment with TAF.