Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus co-formulated efavirenz, emtricitabine, and tenofovir for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3 trial, analysis of results after 48 weeks

Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate versus ritonavir-boosted atazanavir plus co-formulated emtricitabine and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3, non-inferiority trial

The safety of tenovir disoproxil fumarate (TDF) was assessed in two double-blind, placebo-controlled studies. Furthermore, we retrospectively collected 19 cases of TDF-associated tubular dysfunction. The incidence of renal events was similar among the active TDF groups and the placebo group in the two double-blind, placebo-controlled studies. Proximal tubulopathy was diagnosed 6.89 +/- 5.51 months after TDF therapy started. All abnormalities normalized within 4.7 +/- 2.94 weeks after drug discontinuation.

Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: two randomised, double-blind, phase 3, non-inferiority trials

Background: Tenofovir disoproxil fumarate (TDF) is a major antiretroviral therapy for Thai human immunodeficiency virus (HIV) infected adults. TDF is associated with a decrease in renal function. There is limited data about the use of TDF with the incidence and time to renal impairment and chronic kidney disease (CKD) in Thai HIV-infected adults. Objectives: To study the association of TDF with the incidence rate and duration of renal impairment and CKD in Thai patients. Methods: A retrospective cohort study in Thai naïve HIV-infected adults was conducted to compare the incidence rate and time to renal impairment and CKD in TDF and non-TDF groups. The incidence rate was analyzed by person-time. Time to renal impairment and CKD were analyzed by Kaplan-Meier curves and log-rank tests. Results: A total of 1,400 patients were enrolled. The incidence rates of renal impairment in TDF and non-TDF groups were 27.66/1,000 and 5.54/1,000 person-years. The rate ratio was 4.99 (95% confidence interval [CI] 2.66–9.35). The incidence rates of CKD in both groups were not significantly different. Themean difference of eGFR between the TDF and non-TDF groups was 1.92 ml/min/1.73 m2 (p = 0.022). Time to onset of renal impairment between the TDF and non-TDF groups was found to differ by approximately 20 months. Conclusion: The incidence rate of renal impairment was about five times higher in the TDF group. A rapid decline of eGFR occurred in the first 2–3 years of treatment. Therefore, the renal function of HIV-infected patients should be monitored so that the severity of renal impairment could be evaluated and CKD could be prevented.

Effect of Pegylated Interferon Plus Tenofovir Combination on Higher Hepatitis B Surface Antigen Loss in Treatment-naive Patients With Hepatitis B e Antigen -positive Chronic Hepatitis B: A Real-world Experience

It is unclear whether tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF) is more effective for preventing hepatocellular carcinoma (HCC) development in patients with chronic hepatitis B (CHB). In this study, we compared the effectiveness of these two antiviral agents for preventing HCC. We included treatment-naïve CHB patients undergoing antiviral therapy with TDF only (TDF group) or a TAF-based regimen (TAF group) at three academic teaching hospitals from 2012 to 2019. The TAF group included patients receiving TAF as first-line treatment and patients switching from TDF to TAF. Patients with decompensated cirrhosis or HCC at enrollment were excluded. Cumulative probabilities of HCC were assessed using Kaplan-Meier methodology. In total, 2,117 patients were included: 1,832 in the TDF group and 285 in the TAF group. The annual HCC incidence was not significantly different between TDF and TAF groups: 1.66 vs. 1.19 per 100 person-years [PY], respectively (multivariate analysis: adjusted hazard ratio [HR] 0.774 [reference: TDF group]; p=.438). Male, liver cirrhosis, hepatitis B e antigen negativity, Fibrosis-4 index>3.25 and low albumin were independently associated with a higher risk of HCC. Propensity score-matched and inverse probability of treatment weighting analyses yielded similar results: 1.56 vs. 1.19 per 100 PY, respectively (HR 1.175; p=.708) and 1.66 vs. 1.29 per 100 PY, respectively (HR 0.888; p=.446). The risk of HCC development was not significantly different between TDF and TAF groups of CHB patients. Further studies with a larger sample size and longer follow-up are required to validate our results.

Tenofovir disoproxil fumarate (TDF), compared to tenofovir alafenamide (TAF), leads to lower body weight and plasma lipids by an unknown mechanism. We hypothesize that TDF, when absorbed, may damage enterocytes of the proximal duodenum, leading to reduced absorption of nutrients. People with human immunodeficiency virus, without significant gastrointestinal symptoms, receiving a regimen containing TDF (n = 12) or TAF (n = 12), underwent esophagogastroduodenoscopies. Plasma/serum concentrations of nutrients absorbed from proximal duodenum and serum intestinal fatty acid-binding protein (I-FABP), a marker of enterocyte damage, were measured. Cytochrome c oxidase/succinate dehydrogenase (COX/SDH) staining and electron microscopy (EM) were conducted to evaluate mitochondria. Five patients in the TDF group (1 celiac disease [excluded from further analyses], 1 Helicobacter gastritis, and 3 esophagitis) and 2 in the TAF group (2 esophagitis) had a pathological finding in esophagogastroduodenoscopy. Villi were flatter (337 [59] vs 397 [42] μm; P = .016), crypts nonsignificantly deeper (200 [46] vs 176 [27] μm; P = .2), and villus-to-crypt ratio lower (1.5 [0.42] vs 2.5 [0.51]; P = .009) in the TDF versus TAF group (mean [standard deviation]). I-FABP concentration was higher in the TDF versus TAF group (3.0 [1.07] vs 1.8 [0.53] ng/mL; P = .003). The TDF group had numerically but not statistically significantly lower concentrations of folate and vitamins A, B1, D, and E. COX/SDH staining and EM showed similar mitochondrial damage in both groups. Duodenal villous alterations may explain TDF-associated decrease in body weight and plasma lipids. Larger studies are needed to evaluate concentrations of nutrients absorbed from duodenum among TDF users.. NCT05326971; EudraCT 2022-000849.

Switching from efavirenz, emtricitabine, and tenofovir disoproxil fumarate to tenofovir alafenamide coformulated with rilpivirine and emtricitabine in virally suppressed adults with HIV-1 infection: a randomised, double-blind, multicentre, phase 3b, non-inferiority study

Antiviral therapy after curative treatment of hepatocellular carcinoma in patients with chronic hepatitis B infection: Is tenofovir or entecavir preferred?

Acute-on-chronic liver failure (ACLF) can be triggered by reactivation of chronic hepatitis B (CHB). Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are now the most potent antiviral agents for CHB. This study aimed to compare the short-term safety and efficacy of TDF with ETV in the treatment of ACLF due to reactivation of CHB [hepatitis B virus (HBV)-ACLF]. In total, 67 consecutive patients with HBV-ACLF were divided into TDF group (n=32) receiving daily TDF (300 mg/d) and ETV group (n=35) receiving daily ETV (0.5 mg/d). They were prospectively followed-up and the primary endpoint was overall survival at 3 months. At 2 weeks, the TDF group had significantly higher HBV-DNA reduction (P=0.003), lower HBV-DNA level (P=0.001), higher rate of HBV-DNA undetectbility (P=0.007), lower Child-Turcotte-Pugh (CTP; P=0.003), and model for end-stage liver disease (P=0.002) scores than the ETV group. At 3 months, HBV-DNA was undetectable in all survived patients; CTP (P=0.970) and model for end-stage liver disease (P=0.192) scores were comparable between the 2 groups, but markedly lower than at baseline (P<0.01); the TDF group had significantly higher cumulative survival rate than the ETV group (P=0.025). The white blood cell count (hazard ratio, 2.726; 95% confidence interval, 2.691-7.897; P=0.000), and HBV-DNA reduction (hazard ratio, 0.266; 95% confidence interval, 0.033-0.629; P=0.013) at 2 weeks were independent predictors for mortality. Both drugs were well tolerated. The short-term efficacy of TDF was superior to ETV for the treatment of HBV-ACLF. The white blood cell count and HBV-DNA reduction at 2 weeks were independent predictors for mortality at 3 months.

BackgroundCurrent clinical guidelines recommend treating chronic hepatitis B virus (HBV) infection in a minority of cases, but there are relatively scarce data on evolution or progression of liver inflammation and fibrosis in cases of chronic HBV (CHB) that do not meet treatment criteria. We aimed to assess the impact of TDF on liver disease, and the risk of renal impairment in treated CHB patients in comparison to untreated patients.MethodsWe studied a longitudinal ethnically diverse CHB cohort in the UK attending out-patient clinics between 2005 and 2018. We examined TDF treatment (vs. untreated) as the main exposure, with HBV DNA viral load (VL), ALT, elastography scores and eGFR as the main outcomes, using paired tests and mixed effects model for longitudinal measurements. Additionally, decline of eGFR during follow-up was quantified within individuals by thresholds based on clinical guidelines. Baseline was defined as treatment initiation for TDF group and the beginning of clinical follow-up for untreated group respectively.ResultsWe included 206 adults (60 on TDF, 146 untreated), with a median ± IQR follow-up duration of 3.3 ± 2.8 years. The TDF group was significantly older (median age 39 vs. 35 years, p = 0.004) and more likely to be male (63% vs. 47%, p = 0.04) compared to the untreated group. Baseline difference between TDF and untreated groups reflected treatment eligibility criteria. As expected, VL and ALT declined significantly over time in TDF-treated patients. Elastography scores normalised during treatment in the TDF group reflecting regression of inflammation and/or fibrosis. However, 6/81 (7.4%) of untreated patients had a progression of fibrosis stage from F0-F1 to F2 or F3. There was no evidence of difference in rates or incidence of renal impairment during follow-up in the TDF vs. untreated group.ConclusionsRisk of liver inflammation and fibrosis may be raised in untreated patients compared to those receiving TDF, and TDF may benefit a larger percentage of the CHB population.

A complete virological response is closely related to the long-term outcome of patients with chronic hepatitis B and prevention of emerging HBV mutations. We aimed to evaluate the efficacy of tenofovir disoproxil fumarate (TDF) monotherapy compared to entecavir-adefovir dipivoxil (ETV-ADV) combination therapy in patients with suboptimal responses to long-term lamivudine-adefovir dipivoxil (LAM-ADV) therapy for nucleoside analogue-resistant chronic hepatitis B. Patients (n=60) were randomized to TDF monotherapy or ETV-ADV combination therapy for 96 weeks. All patients had the rt204I/V mutation and serum HBV DNA was measured (>60 IU/ml) during LAM-ADV therapy. The primary end point was a complete virological response (HBV DNA <20 IU/ml) at week 96. The median duration of prior LAM-ADV rescue therapy was 43 (7-108) months. A complete virological response was achieved in 86.6% and 53.3% of patients in the TDF and ETV-ADV groups, respectively, at week 96 (P=0.005). Reduction in serum HBV DNA was significantly greater in the TDF group than in ETV-ADV group (-3.2 ±1.2 versus -2.6 ±1.2; P=0.01). Hepatitis B e antigen loss (22.2% versus 16.6%; P=0.731) and biochemical responses (76.7% versus 73.3%; P=0.766) were not different between the TDF and ETV-ADV groups. No newly emerged mutations were detected. Both therapies demonstrated favourable safety profiles. TDF therapy achieved a better complete virological response than ETV-ADV therapy in chronic hepatitis B patients with suboptimal response to long-term LAM-ADV rescue therapy. (KCT0000627).

Background &amp; Aims: Chronic hepatitis B (CHB) infection can cause liver cirrhosis and hepatocellular carcinoma. In this study, it was aimed to evaluate the efficacy of tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide fumarate (TAF) on clinical parameters, glomerular filtration rate (GFR), and phosphorus metabolism in the patients with CHB. Materials and Methods: Eighty-one patients with CHB treated with TDF were included in the study. 27 of them switched from TDF to TAF during the follow-up was considered as TAF group. 54 patients continued TDF were evaluated as TDF group. Demographic, clinical, and laboratory data of the patients were obtained from outpatient follow-up files. Results: The mean ages of the patients were 45±12 and 48±15 in the TDF and TAF groups, respectively. The mean durations of TDF treatment were 31±20 and 52±32 months, respectively. The mean duration of TDF use was significantly higher in the TAF group (0.01). The mean aspartate aminotransferase (AST), alanine aminotransferase (ALT), GFR, and serum phosphorus levels of the patients before/after the TDF treatment were 48/23 U/L, 67/25 U/L, 99/103 ml/min, and 2.9/3.1 mg/dl in the TDF group, respectively. The mean AST, ALT, GFR, and serum phosphorus levels of the patients before the TDF treatment/at the time of the switch/after the TAF treatment were 42/22/21 U/L, 48/23/22 U/L, 90/100/102 ml/min, and 2.8/2.3/2.9 mg/dl in the TAF group, respectively. Decrease in the mean values of the transaminases after the TDF treatment in the both groups and increase in the mean level of phosphorus after the switching were found significant (p

Background This retrospective, multi-center cohort study aimed to compare the effects of Integrase Strand Transfer Inhibitor (INSTI) based therapies containing tenofovir disoproxil fumarate (TDF)/ Emstristabin (FTC) /Dolutegravir (DTG), TDF/FTC/Cobicistat (C)/Elvitegravir(EVG), TDF/FTC/Raltegravir (RAL) and tenofovir alafenamide (TAF)/FTC/Bictegravir (BIC), TAF/FTC/c/EVG) combinations on bone metabolism, lipid profile, and renal function in people living with HIV (PLWH). Methods Adults aged ≥ 18 years receiving antiretroviral therapy (ART) for ≥ 12 months were followed for ≥ 24 months. Data were obtained from HIV/AIDS clinic records and hospital databases, including demographics, laboratory values (HIV RNA, CD4 + T lymphocyte count, creatinine, eGFR, ALT), lipid profiles (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides), and DEXA results. Statistical significance was defined as a p-value less than 0.05. Findings: The treatment outcomes of 901 HIV-infected individuals from 9 centers in Türkiye were evaluated. After applying exclusion criteria, data from 845 individuals were included: 462 in the TDF group (mean age 43.25 ± 12.35) and 383 in the TAF group (mean age 41.75 ± 12.08) (p = 0.082). The proportion of female patients was 18.4% in the TDF group and 13.6% in the TAF group (p = 0.058). In the TDF group, 77.2% were treatment-naïve, compared to 52.2% in the TAF group (p &lt; 0.001). At 24 months, HIV RNA levels were 14218.43 ± 233947.64 IU/ml in the TDF group and 3247.15 ± 55371.53 IU/ml in the TAF group (p &lt; 0.001). Although CD4 levels were higher at baseline in the TAF group (p &lt; 0.001), the TDF group showed a greater increase at 48 months (p = 0.013). ALT normalization was better in the TDF group, while total and non-HDL cholesterol levels were higher in the TAF group. Conclusion TDF and TAF-containing INSTI-based regimens exhibit distinct impacts on lipid profiles and immune function in PLWH. The early advantages of TAF in viral load reduction diminish over time, contrasting with the long-term benefits of TDF in terms of CD4 counts, ALT levels, and non-HDL cholesterol. These findings highlight the necessity of individualized treatment in selecting ART regimens.

Efficacy and safety of dolutegravir with emtricitabine and tenofovir alafenamide fumarate or tenofovir disoproxil fumarate, and efavirenz, emtricitabine, and tenofovir disoproxil fumarate HIV antiretroviral therapy regimens started in pregnancy (IMPAACT 2010/VESTED): a multicentre, open-label, randomised, controlled, phase 3 trial