Tenofovir Alafenamide Research Articles

Tenofovir alafenamide compared to tenofovir disoproxil fumarate, induces dysglycemia, and dyslipidemia in Wistar rats.

To determine the metabolic effects of tenofovir alafenamide (TAF) compared to tenofovir disoproxil fumarate (TDF) in vivo . Male Wistar rats ( Rattus novergicus , 250-300 g body weight) were divided into three groups ( n = 8) and orally treated daily with 1.0 ml distilled water (group 1), TAF (0.42 mg/kg) (group 2), or TDF (5.0 mg/kg) (group 3), respectively, for 56 days. Glucose tolerance tests were done before the animals were sacrificed by halothane overdose, and blood was collected by cardiac puncture for the analysis of plasma lipids, electrolytes, and insulin. The kidney and pancreatic tissues were excised and homogenized to measure oxidative stress. Compartmentation of TAF and TDF was determined in NRK-52 and peripheral blood mononuclear cells (PBMCs). There were no significant differences in weight gain among controls, TAF- or TDF-treated rats. TAF-treated rats had significantly increased fasting blood glucose (FBG), fasting plasma insulin (FPI), insulin resistance, impaired glucose tolerance, and dyslipidemia compared to control or TDF-treated rats, respectively. There was increased lipid peroxidation in the pancreas of TAF-treated compared to TDF-treated or control animals, respectively. TDF- treated rats presented with symptoms of Fanconi syndrome compared to TAF-treated or control animals, respectively. Kidney homogenates from TDF-treated animals had significantly reduced antioxidant enzyme activity compared to TAF-treated animals or controls, respectively. Intracellular concentrations of TAF were significantly higher than TDF in both NRK-52E cells and PBMC, respectively. TAF treatment is weight-neutral and causes dysglycemia, and dyslipidemia but not Fanconi syndrome compared to TDF.

Efficacy and Safety of Tenofovir Amibufenamide and Tenofovir Alafenamide for First-Time HBV-Related Decompensated Cirrhosis.

Clinical studies of tenofovir amibufenamide (TMF) and tenofovir alafenamide (TAF) treatment in patients with HBV-related decompensated cirrhosis (HBV-DC) are limited. This study evaluated the efficacy and safety of TMF versus TAF in naive-treated patients with first-time HBV-DC. Based on the antiviral drug used, patients were categorised into the TMF group and the TAF group. Virological and serological responses, hepatic and renal functions and blood lipid changes in both groups were evaluated during 48 weeks of treatment. A total of 98 patients were enrolled, 45 in the TMF group and 53 in the TAF group. At 48 weeks of treatment, the proportions of patients who achieved complete virological response (CVR) were 85.7% and 90.7%, respectively (p = 0.791). Improvement of at least 2 points in Child-Turcotte-Pugh scores was observed in 64.3% versus 79.1% (p = 0.169) of the patients. There were no significant changes in serum creatinine, estimated glomerular filtration rate or total cholesterol from baseline to week 48 between the two groups. Cystatin C remained stable in the TMF group but increased over time in the TAF group (p < 0.001). Low-density lipoprotein cholesterol remained stable in the TMF group but increased significantly in the TAF group at week 48 (p = 0.015). These results suggest that both TMF and TAF can rapidly suppress HBV replication, improve hepatic function and have no negative effects on renal function among patients with HBV-DC. Regarding lipid metabolism, both showed a better safety, while regular monitoring of blood lipid levels is recommended.

Effect of Tenofovir Alafenamide Fumarate on the outcomes of hospitalized COVID-19 patients: a prospective, block-balanced, open-label, randomized controlled trial

BackgroundThe global effort to cure COVID-19 is still ongoing. Thus, a prospective, block-balanced, open-label, randomized controlled trial was conducted to evaluate how Tenofovir Alafenamide Fumarate affects hospitalized COVID-19 patients’ outcomes.MethodsThe intervention and control groups of 60 hospitalized COVID-19 patients were randomly allocated. Along with normal medication, the intervention group received 25 mg of tenofovir orally daily for seven days. The control group got normal therapy, including remdesivir and corticosteroids. ICU hospitalization duration, laboratory data, fever, dyspnea, arterial blood oxygen saturation with and without an oxygen face mask, mechanical ventilation, and mortality were the outcomes.ResultsSixty of 236 eligible patients between September 2020 and February 2021 were enrolled. The intervention group had a mean age (±SD) of 61.33 (±13.09) years and the control group 60.03 (±18.03). Sixteen (53.3%) intervention patients and 15 (50.0%) control patients were males. The intervention group had fewer mechanical ventilation and ICU days. Tenofovir Alafenamide Fumarate did not improve fever, dyspnea, oxygen saturation with or without a face mask or nasal cannula, or laboratory data including WBC, ESR, CRP, AST, ALT, AlkP, total and direct bilirubin, in COVID-19 patients.ConclusionAccording to this pilot trial, Tenofovir Alafenamide Fumarate, along with conventional treatment, significantly reduced mechanical ventilation and ICU stay in COVID-19 patients. Further thorough research is necessary to verify this conclusion.

Birth outcomes following bictegravir exposure during pregnancy.

Bictegravir is increasingly prescribed as a co-formulated tablet with tenofovir alafenamide and emtricitabine to pregnant persons with HIV (PWH) despite limited pregnancy and birth outcome data. We sought to provide birth outcome data following exposure to bictegravir during pregnancy. We conducted a descriptive analysis of infants born to pregnant PWH 18-45 years of age enrolled in at least one Pediatric HIV/AIDS Cohort Study (PHACS)-affiliated study who received bictegravir for ≥7 days during pregnancy and completed follow-up through delivery. The outcomes of interest were gestational age at birth, preterm birth (<37 weeks' gestation), gestational-age adjusted birth weight (BWZ) and length (BLZ) z-scores, small for gestational age (SGA, birthweight <10th percentile), congenital anomalies, neonatal deaths in the first 28 days of life, and infant HIV status. A total of 177 infants born to 170 unique PWH were exposed to bictegravir for ≥7 days during gestation; 55% were exposed to bictegravir from the time of conception. Median gestational age at birth was 38.1 weeks. The prevalence of preterm birth was 15.8% and SGA was 9.3%. Mean BWZ and BLZ were -0.48 and 0.03. No neonatal deaths or perinatal HIV transmissions were reported. Among 126 infants exposed to first-trimester bictegravir, 7 (5.6%) had major congenital anomalies with no specific pattern suggestive of a syndrome. These findings provide preliminary data without significant safety concerns for fetal bictegravir exposure in this United States cohort. Comparative data and continued surveillance of outcomes among infants exposed to bictegravir during gestation are warranted.

Neuropsychiatric adverse events in tenofovir disoproxil fumarate- and tenofovir alafenamide-based HIV therapy and prophylaxis: a systematic review and meta-analysis.

Tenofovir is integral to antiretroviral therapy (ART) and preexposure prophylaxis (PrEP) for HIV, but its neuropsychiatric adverse events (NPAEs) have not been systematically investigated. This systematic review aims to characterize common NPAEs during tenofovir-based ART and PrEP and to assess tenofovir's specific role in their emergence. Four literature databases and three trial registries were searched up to December 31, 2023, for randomized controlled trials reporting NPAEs in treatment-naïve adults receiving tenofovir-based ART or PrEP. Meta-analyses compared tenofovir (with/without emtricitabine) to placebo and tenofovir alafenamide- to tenofovir disoproxil fumarate-based regimens. Sixty-nine trials (62 on ART, 7 on PrEP) with 29 340 patients on tenofovir-based therapies revealed headache, dizziness, insomnia, and depression as common NPAEs, especially in HIV studies. Meta-analyses of tenofovir (with/without emtricitabine) versus placebo only indicated an increased risk of dizziness (OR 1.32; CI 1.09-1.59; P = 0.004). Comparisons between tenofovir alafenamide and disoproxil fumarate did not reveal significant differences in NPAE risks, although sensitivity analyses suggested a higher risk of headache with tenofovir alafenamide in HIV studies (OR 1.24; CI 1.01-1.52; P = 0.04). Common NPAEs in tenofovir-based HIV multi-drug regimens highlight the need to screen HIV patients for neuropsychiatric complications. The lack of effect of tenofovir compared to placebo for most analyzable NPAEs suggests that tenofovir itself is mostly safe regarding NPAEs. However, a possible increase in dizziness risk with tenofovir, and a potential rise in headache risk with tenofovir alafenamide- compared to tenofovir disoproxil fumarate-based regimens in HIV therapy, merit further investigation.

Expected Eight-Week Prenatal Versus Twelve-Week Perinatal Tenofovir Alafenamide Prophylaxis to Prevent Mother-To-Child Transmission of Hepatitis B Virus: A Multicenter, Prospective, Open-label, Randomized Controlled Trial.

The course of maternal antiviral prophylaxis to prevent mother-to-child transmission of hepatitis B virus (HBV-MTCT) varies greatly, and it has not been demonstrated in a randomized controlled study. In this multicenter, open-label, randomized controlled trial, eligible pregnant women with HBV DNA of 5.3-9.0 log10 IU/mL who received tenofovir alafenamide fumarate (TAF) from the first day of 33 gestational weeks to delivery (expected eight-week) or to four-week postpartum (expected twelve-week) were randomly enrolled at a 1:1 ratio and followed until six-month postpartum. All infants received standard immunoprophylaxis (hepatitis B immunoglobulin and vaccine). The primary endpoint was the safety of mothers and infants. The secondary endpoint was infants' HBV-MTCT rate at seven months of age. Among 119 and 120 intention-to-treat pregnant women, 115 and 116 women were followed until delivery, and 110 and 112 per-protocol mother-infant dyads in two groups completed the study. Overall, TAF was well tolerated, no one discontinued therapy due to adverse events (0/239, 0%, 95% confidence interval [CI] 0%-1.6%), and no infant had congenital defects or malformations at delivery (0/231, 0%, 95% CI 0%-1.6%). The infants' physical development at birth (n=231) and at seven months (n=222) were normal. Furthermore, 97.0% (224/231, 95% CI 93.9%-98.5%) of women achieved HBV DNA <5.3 log10 IU/mL at delivery. The intention-to-treat and per-protocol infants' HBV-MTCT rates were 7.1% (17/239, 95% CI 4.5%-11.1%) and 0% (0/222, 95% CI 0%-1.7%) at seven months of age. Comparatively, 15.1% (18/119, 95% CI 9.8%-22.7%) versus 18.3% (22/120, 95% CI 12.4%-26.2%) of women in the two groups had mildly elevated alanine aminotransferase levels at three-month and six-month postpartum, respectively (P=0.507); notably, no one experienced alanine aminotransferase flare (0% [0/119, 95% CI 0%-3.1%] versus 0% [0/120, 0%-3.1%]). Maternal TAF prophylaxis to prevent HBV-MTCT is generally safe and effective, and expected eight-week prenatal duration is feasible. ClinicalTrials.gov, NCT04850950.

7172 Osteoporosis Associated with Antiretroviral Therapy - Case report

Abstract Disclosure: C.E. Guillen Lopez: None. L.A. Sanchez Ato: None. A. Patel: None. A. Molkina: None. T. Ayub: None. L. Robles: None. A. Arce Gastelum: None. Osteoporosis presents a substantial public health challenge, contributing significantly to morbidity and mortality through fractures. While postmenopausal osteoporosis is common, secondary osteoporosis affects a significant number of patients, including over 30% of postmenopausal and 50-80% of men. People living with HIV (PLWH) experience age-related medical comorbidities earlier and more extensively than those without HIV. The compromised bone health in PLWH is attributed to factors associated with the virus, antiretroviral therapy (ART) side effects, and health disparities such as inadequate nutrition, low body weight, hypogonadism, vitamin D deficiency, and increased recreational substance use. More recently, it has become apparent that vertebral fractures are more common in PLWH, with a prevalence of 11.1% and a 2.30-fold more significant risk than the general population. Low bone mass density (BMD) is twice as common in PLWH, increasing to 3 times as common in PLWH on ART. ART initiation leads to transient bone loss with nucleotide reverse transcriptase inhibitors such as tenofovir disoproxil fumarate (TDF) and protease inhibitors, causing higher BMD loss. In contrast, integrase and specific reverse-transcriptase inhibitors have minimal adverse effects on BMD. The newer formulation, tenofovir alafenamide (TAF), is believed to have a more favorable impact on bone health than TDF. The repercussions of diminished bone health, particularly osteoporotic fractures, have significant medical and economic implications. They are leading to early mortality, disability, and a loss of independence. The HIV Medicine Association (HIVMA) and Infectious Diseases Society of America (IDSA) recommend BMD screening for all HIV-infected patients at 50 years. 58-year-old male PLWH reveals a history of osteoporosis with multiple spinal (L1, L4-5, S1) and bilateral wrist fractures on TDF for 15 years. The patient has been treated with bisphosphonates. Alendronate was initially prescribed, but due to acid reflux side effects, zoledronic acid was a better option. Despite various ART regimens, Dolutegravir/Lamivudine was started four years ago without further fractures. Recent bone density assessments showed improvement in the lumbar spine, returning to a normal range with a T-score of 0.6. However, the left femoral neck remains at -2.5, and the right femoral neck is at -2.2, showing minimal change. To enhance BMD in PLWH on ART, transitioning to alternatives with lower bone loss associations and using bisphosphonates as tolerated are suggested. As the HIV-infected population ages, proactive screening for low BMD is vital to manage evolving health needs and prevent bone-related complications. A holistic approach includes evaluation for secondary etiologies of osteoporosis, medical treatment, and vitamin D and calcium supplementation. Presentation: 6/3/2024

12553 Severe Hyperglycemia After Initiation Of Bictegravir Antiretroviral Therapy With Resolution Upon Discontinuation

Abstract Disclosure: S. Hudson: None. J. Aurora: None. K. Grossman: None. L. Kogelman: None. A.G. Pittas: None. Background: Antiretroviral therapy (ART) containing bictegravir (BIC), a second-generation integrase strand transfer inhibitor (INSTI), is a first-line treatment for HIV. There are mixed reports of INSTIs causing adverse metabolic effects, such as weight gain and hyperglycemia. There are cases of BIC causing hyperglycemia and diabetic ketoacidosis (DKA) within weeks to months following initiation; however, this has not been reported in clinical trials (1). It is unclear whether discontinuing BIC resolves hyperglycemia. We report a case of a patient with prediabetes who developed severe hyperglycemia after switching to a BIC-containing ART. The discontinuation of BIC resulted in significant improvement in glycemia, leading to the de-escalation of diabetes pharmacotherapy. Clinical Case: A 36-year-old woman with obesity was diagnosed with HIV during pregnancy, which was complicated by gestational diabetes mellitus. After pregnancy, she had prediabetes. Her initial ART was darunavir/cobicistat/emtricitabine/tenofovir alafenamide. Due to intolerable GI side effects, six years later, she was switched to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). Laboratory tests four months before starting BIC/FTC/TAF were consistent with prediabetes (HbA1c 6.4%, non-fasting blood glucose of 118 mg/dL). After one month, she was started on metformin when her HbA1c increased to 9.1% with a non-fasting blood glucose of 332 mg/dL. Another month later, HbA1c increased to 12.8% with a non-fasting blood glucose of 685 mg/dL without DKA. She was hospitalized for diabetes management. There were no significant changes in weight, viral load, or CD4 count. A search for secondary causes of hyperglycemia (diabetogenic medications, hypercortisolism, and autoimmune diabetes) was not revealing. She was discharged on metformin and insulin glargine. Her HIV regimen was switched to FTC/TAF and doravirine due to suspicion of BIC-induced hyperglycemia. After five months, she developed symptoms of hypoglycemia, and her estimated HbA1c by continuous glucose monitoring was 6.3%. Insulin glargine was discontinued. While on metformin, HbA1c three months later was 6.3%. Two years later on metformin and linagliptin: HbA1c was 6.1% and beta-cell function did not reveal insulin deficiency or resistance (non-fasting blood glucose 96 mg/dL, insulin 13.5 uIU/mL [RR 2.6-24.9 mIU/mL], C-peptide 3.7 ng/mL [RR 1.1-4.4 ng/mL]). Conclusion: Patients with HIV and a history of obesity and/or dysglycemia who are switched to a BIC-containing ART regimen should be educated and monitored for acute hyperglycemia. This may be due to impaired beta-cell function and/or insulin resistance; however, further research is needed to understand the mechanism. An alternative ART regimen should be considered if hyperglycemia develops. Reference: 1. Nolan NS, et al. Open Forum Infect Dis. 2021;16;8(5): ofab077. Presentation: 6/3/2024

Bictegravir alters glucose tolerance in vivo and causes hepatic mitochondrial dysfunction

Growing evidence associates antiretroviral therapies containing integrase strand transfer inhibitors or tenofovir alafenamide (TAF) with increased weight gain and metabolic diseases, but the underlying mechanisms remain unclear. This study evaluated the impact of lamivudine, dolutegravir (DTG), bictegravir (BIC), tenofovir disoproxil fumarate, and TAF on metabolic alterations, and explored glucose homeostasis and mitochondrial stress as potential mechanisms. These pathways were analyzed both in vivo (C57BL/6J mice treated with the abovementioned drugs or vehicle for 16 weeks) and in vitro (in Hep3B cells). Mice treated with BIC exhibited higher glucose levels and a slower decrease during a glucose tolerance test. Functional enrichment analyses of livers from antiretroviral-treated mice revealed that only BIC altered the cellular response to insulin and induced a gluconeogenic-favoring profile, with Fgf21 playing a significant role. In vitro, BIC significantly reduced hepatocyte glucose uptake in a concentration-dependent manner, both under basal conditions and post-insulin stimulation, while the other drugs produced no significant changes. Hep3B cells treated with clinically relevant concentrations of BIC exhibited significant alterations in the mRNA expression of enzymes related to glucose metabolism. Both DTG and BIC reduced mitochondrial dehydrogenase activity, but only BIC increased reactive oxygen species, mitochondrial membrane potential, and cellular granularity, thereby indicating mitochondrial stress. BIC promoted mitochondrial dysfunction, modified carbohydrate metabolism and glucose consumption in hepatocytes, and altered glucose tolerance and gluconeogenesis regulation in mice. These findings suggest that BIC contributes to insulin resistance and diabetes in people living with HIV, warranting clinical studies to clarify its association with carbohydrate metabolism disorders.

High plasma concentration of tenofovir alafenamide in people living with HIV with ABCB1 genetic variants

ObjectivesWe aimed to analyze the relationships between single nucleotide polymorphisms in the ATP-binding cassette transporter B1 (ABCB1) and G2 (ABCG2) genes and plasma concentrations of tenofovir alafenamide (TAF), tenofovir (TFV), and emtricitabine (FTC). MethodsWe recruited 10 people living with HIV receiving once-daily treatment with a single tablet containing TAF (25 mg), FTC (200 mg), and bictegravir (50 mg). Peripheral blood samples were collected at 0, 1, 2, 3, 4, 6, 8, 12, and 24 h after administration. Plasma concentrations of TAF, TFV, and FTC were quantified using liquid chromatography-tandem mass spectrometry. Genotyping for allelic variants of ABCB1, including 1236 C>T (rs1128503), 2677 G>T/A (rs2032582), 3435 C>T (rs1045642), 4036 A>G (rs3842) and ABCG2 421 C>A (rs2231142), was performed using TaqMan Drug Metabolism Assays. ResultsNone of the genotypes for ABCB1 1236 C>T, 2677 G>T/A, 3435 C>T, and ABCG2 421 C>A exhibited correlations with plasma concentrations of TAF, TFV, and FTC. In contrast, individuals with the ABCB1 4036 AG genotype (188.7 ng/mL, n = 3) exhibited a significantly higher mean peak plasma concentration of TAF than those with the ABCB1 4036 AA genotype (67.7 ng/mL, n = 7) (p = 0.0167). However, these genotypes did not affect the elimination of terminal half-lives of TAF. ConclusionsThe allelic variant ABCB1 4036 A>G is associated with reduced protein expression and function of ABCB1. Individuals with this genetic variant exhibited significantly high peak plasma concentrations of TAF, potentially due to the reduced expression of efflux transporters in the intestines linked to this variant.

Proteinuria Outcomes of Tenofovir Alafenamide Fumarate (TAF) vs. Tenofovir Disoproxil Fumarate (TDF) Regimens for Treatment of HIV, HBV, and HIV PrEP: A Systematic Literature Review and Meta-Analysis

Proteinuria Outcomes of Tenofovir Alafenamide Fumarate (TAF) vs. Tenofovir Disoproxil Fumarate (TDF) Regimens for Treatment of HIV, HBV, and HIV PrEP: A Systematic Literature Review and Meta-Analysis

Evaluation of the Effect of Racial Differences on Longitudinal Trajectories of Kidney Function in People with HIV (PWH) on Tenofovir Alafenamide (TAF)-Based Antiretroviral Treatment (ART) Regimens

Evaluation of the Effect of Racial Differences on Longitudinal Trajectories of Kidney Function in People with HIV (PWH) on Tenofovir Alafenamide (TAF)-Based Antiretroviral Treatment (ART) Regimens

Drug-drug interactions between gender-affirming hormone therapy and antiretrovirals for treatment/prevention of HIV.

Transgender persons face a greater burden of HIV compared to cisgender counterparts. Concerns around drug-drug interactions (DDIs) have been cited as reasons for lower engagement in HIV care and lower pre-exposure prophylaxis (PrEP) uptake among transgender populations. It is therefore imperative for hormone therapy, PrEP and antiretroviral therapy providers to understand the DDI potential between these therapies. Studies of tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) PrEP with feminizing hormone therapies (FHTs) show reduced plasma tenofovir concentrations, but intracellular concentrations of tenofovir-diphosphate are not reduced. Efficacy of PrEP is expected to be maintained despite this interaction. Masculinizing hormone therapies have no effect on tenofovir concentrations but may increase FTC to a nonclinically relevant extent. No interactions between FHT and cabotegravir or tenofovir alafenamide have been demonstrated. Administration of TDF/FTC PrEP has no effect on hormone levels in transmen or transwomen. PrEP is expected to be effective and safe in transpersons and should be provided to high-risk individuals regardless of gender affirming hormone use. Enzyme inducing/inhibiting antiretroviral therapy may decrease or increase, respectively, the concentrations of FHT and masculinizing hormone therapy. Unboosted integrase inhibitors or enzyme neutral non-nucleoside reverse transcriptase inhibitors are not expected to affect and are not affected by gender affirming hormones and can be considered in transmen and transwomen. Overlapping toxicities including weight gain, dyslipidaemia, cardiovascular disease and bone density effects should be considered, and antiretroviral modifications can be made to minimize toxicities. Interactions between supportive care medications should be assessed to avoid chelation interactions and hyperkalaemia.

Brief Report: Subsequent Pregnancies in the IMPAACT 2010/VESTED Trial: High Rate of Adverse Outcomes in Women Living With HIV

Introduction: Women with HIV (WHIV) have higher risks of adverse pregnancy outcomes, particularly in the absence of antiretroviral treatment (ART), and timing of ART may impact risk. Methods: In the International Maternal Pediatric Adolescent AIDS Clinical Trials 2010/VESTED study, 643 pregnant WHIV in 9 countries were randomized in a 1:1:1 ratio to initiate ART: dolutegravir (DTG)+emtricitabine (FTC)/tenofovir alafenamide (TAF), DTG+FTC/tenofovir disoproxil fumarate (TDF), or efavirenz (EFV)/FTC/TDF. We describe adverse pregnancy outcomes in women with a subsequent pregnancy during 50 weeks of postpartum follow-up: spontaneous abortion (&lt;20 weeks), stillbirth (≥20 weeks), preterm delivery (&lt;37 weeks), and small for gestational age. Results: Of 643 women, 19 (3%) had 20 subsequent pregnancies while receiving ART at conception: DTG/FTC/TAF (3), DTG/FTC/TDF (2), EFV/FTC or lamivudine (3TC)/TDF (12), EFV/abacavir/3 TC (1), and no ART (1). Four spontaneous abortions, 3 stillbirths, and 1 induced abortion occurred. Three (25%) of 12 liveborn infants were preterm (24, 26, and 36 weeks of gestation). Only 12 subsequent pregnancies (60%) resulted in live birth, and at least 1 adverse pregnancy outcome occurred in 11 of 19 (58%) (induced abortion excluded). Of 7 women who experienced spontaneous abortion/stillbirth in the subsequent pregnancy, 4 experienced a stillbirth and 1 a neonatal death as outcomes of their earlier index pregnancy. No congenital anomalies were reported. Conclusions: Adverse pregnancy outcomes were common in this cohort of WHIV who conceived on ART shortly after an index pregnancy, 35% ended in stillbirth or spontaneous abortion. The majority of fetal losses occurred in women with recent prior pregnancy loss. Data from larger cohorts of WHIV conceiving on ART and surveillance are needed to elucidate rates and predictors of adverse pregnancy outcome.

Tenofovir alafenamide versus entecavir in treating patients with chronic hepatitis B: A meta-analysis

Background: The superiority between TAF and ETV remains unclear. Which is the best choice for patients with CHB? Thus, this meta-analysis aimed to evaluate the efficacy and safety of TAF and ETV for patients with CHB.Methods: MEDLINE/PubMed, Cochrane Library, EMBASE, Web of Science and CNKI were searched for eligible studies from inception to January 2024 and a meta-analysis was done.Results: 24 trials with a total of 6753 subjects were screened. TAF significantly improved 12- and 24-week complete virological response (CVR), 12-week biochemical response (BR) and 24-week HBeAg loss, but could not improve 48- and 96-week CVR, 24-, 48- and 96-week BR, 96-week HBeAg loss, adverse events, 48-week HBsAg decline and loss, 12-, 24- and 48-week HBeAg seroconversion, 96-week HCC incidence compared to ETV. Subgroup analysis was conducted according to race, research type and switching. Different results were obtained from different subgroups.Conclusions: TAF was superior to ETV at 12- and 24-week CVR, 12-week BR and 24-week HBeAg loss. Race and switching might affect the efficacy of TAF and ETV.

Effects of switching to Dolutegravir/Lamivudine from Tenofovir Alafenamide Fumarate/Emtricitabine/Dolutegravir or Abacavir/Lamivudine/Dolutegravir on body weight and lipid profile in Japanese people living with HIV

BackgroundThe two-drug regimen of dolutegravir/lamivudine (DTG/3TC) is currently an optional antiretroviral therapy (ART). Despite its reported advantages on body weight and lipid profile, the same effects have not yet been reported for Asian population. MethodsWe conducted a single-center retrospective study involving Japanese people living with HIV (PLWH). They were divided into four groups: those who had received abacavir/lamivudine/dolutegravir (ABC/3TC/DTG) and continued the same (ABC-ON group) or switched to DTG/3TC (ABC-OFF group), those who had received tenofovir alafenamide fumarate/emtricitabine/dolutegravir (TAF/FTC/DTG) and continued the same (TAF-ON group) or switched to DTG/3TC (TAF-OFF group). We compared changes in viral load, CD4⁺ cell count, CD4⁺/CD8⁺ ratio, body weight, BMI, lipid profiles, estimated glomerular filtration rate (eGFR), and fibrosis index based on four factors (FIB4-index) between the pre-switch and post-switch period. ResultsOf the 541 PLWH on DTG-based ART, 165, 94, 264 and 18 constituted the ABC-ON, ABC-OFF, TAF-ON, and TAF-OFF groups, respectively. Neither viral rebound nor CD4+decline was observed in the post-switch period in all groups. Multivariate analysis showed significant reduction in total cholesterol, LDL-C and HDL-C in the ABC-OFF group (-6.280, -6.957 and -2.268, p= 0.040, 0.012 and 0.022, respectively), but not in the TAF-OFF group (-3.000, 6.708 and 0.046, p= 0.607, 0.276 and 0.983, respectively). No significant changes were observed in body weight, eGFR, or FIB4-index at 72 weeks after the discontinuation of ABC or TAF. ConclusionsSwitching from ABC/3TC/DTG to DTG/3TC lowered lipids significantly, but not with TAF/FTC/DTG. Neither switch affected body weight or other markers.

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

BackgroundConcerns 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.MethodsA 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).ResultsIn 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).ConclusionsCompared 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.

Eight-year efficacy and safety of tenofovir alafenamide for treatment of chronic hepatitis B virus infection: Final results from two randomised phase 3 trials.

In two phase 3 studies, tenofovir alafenamide (TAF) showed non-inferior efficacy versus tenofovir disoproxil fumarate (TDF), with more favourable renal and bone safety in patients with chronic hepatitis B (CHB). Here, we report the studies' final 8-year results. CHB patients (hepatitis B e antigen [HBeAg]-negative and HBeAg-positive) were randomised (2:1) to double-blind TAF 25 mg/day or TDF 300 mg/day for up to 3 years, followed by open-label (OL) TAF through year 8. Virological, biochemical, serological and fibrosis responses, and safety, including bone and renal parameters, were evaluated. Resistance to TAF was assessed annually by deep sequencing of polymerase/reverse transcriptase and by phenotyping. Among 1298 patients randomised to double-blind TAF (n = 866) or double-blind TDF (n = 432), 775 in the TAF group and 382 in the TDF group received OL TAF, including 180 and 202 who switched from TDF to TAF at year 2 (TDF2y → TAF6y) or year 3 (TDF3y → TAF5y), respectively. At year 8, among patients in the TAF8y, TDF2y → TAF6y and TDF3y → TAF5y groups, 69%, 66% and 73% (missing-equals-failure analysis) and 95%, 94% and 97% (missing-equals-excluded) of patients, respectively, achieved HBV DNA <29 IU/mL. Estimated glomerular filtration rate (Cockcroft-Gault method; eGFRCG) and hip/spine bone mineral density (BMD) remained stable in patients receiving double-blind/OL TAF, with only small declines at year 8. Decreases in eGFRCG and hip/spine BMD observed during double-blind TDF improved after switching to OL TAF. No patients developed resistance to TAF. Long-term TAF treatment exhibited favourable safety and tolerability with high rates of viral suppression and no development of resistance. gov numbers NCT01940341 and NCT01940471.

Advanced, Cutting-Edge RP-HPLC Methodology for the Comprehensive Quantitative Analysis of Assay of Bictegravir, Emtricitabine, and Tenofovir Alafenamide in Co-Formulated Pharmaceutical Products.

In the current study, a simple and economic stability-indicating RP-HPLC method development and validation was carried out to estimate the bictegravir, emtricitabine and tenofovir from the pharmaceutical dosage form. 0.1M ammonium acetate in 0.5% v/v acetic acid solution and 1g of 1-octane sulfonic acid and adjustment of pH to 4.2 with dilute orthophosphoric acid done and methanol (40:60 v/v) was utilized as the mobile phase. The analysis was done using Inertsil ODS 3V (250 x 4.6 mm x 5 µm) column with column temperature kept at 30°C with an injection volume of 20 μL, flow rate of 1.0 ml/ minute and detection was carried out at 260 nm. The method was developed and it was validated according to ICH Q2 (R1) guidelines. The RT of bictegravir, emtricitabine and tenofovir were determined to be 12.23, 3.0 and 8.5 minutes, providing a reliable marker for its identification. The method was found linear from about 50 To 150% Of the target concentration of bictegravir emtricitabine and tenofovir with of 0.999. Significant degradation was observed in acidic, basic and peroxide stress conditions. Hence, it can be concluded that tablets are sensitive to acidic, basic and oxidation stress conditions. RSD for the peak area responses of emtricitabine, 0.03 and 0.03, respectively, indicating that the system is precise. The testing procedure was accurate from about 50 to 150%. Of the target concentration of emtricitabine, tenofovir alafenamide and bictegravir. The method was robust In relation to flow variation, column oven temperature variation, mobile phase variation and pH variation. In conclusion, our proposed RP-HPLC method provides a sensitive, accurate, and precise means of analyzing emtricitabine, tenofovir alafenamide and bictegravir from pharmaceutical dosage forms.

Evaluation of pharmacokinetics of Tenofovir Alafenamide (TAF) and Tenofovir Disoproxil (TDF) in pregnant and postpartum women in South Africa: PrEP-PP PK study

BackgroundThere are few data on tenofovir-diphosphate (TFV-DP) concentrations in pregnant and postpartum women on Tenofovir Disoproxil Fumarate-Emtricitabine (TDF-FTC) or Tenofovir Alafenamide-Emtricitabine (TAF-FTC). MethodsEligible pregnant women were randomized to TDF-FTC or TAF-FTC and followed for 16 weeks (8-weeks pregnant, 8-weeks postpartum) with weekly collection of dried blood spot (DBS) and 4-weekly peripheral blood mononuclear cells (PBMC). PrEP dosing was observed daily via asynchronous videos sent via cell phone. We report geometric means (GM) and their ratios (GMR) with 95% confidence intervals (CIs) for TFV-DP in PBMC and DBS from pregnancy and postpartum. ResultsWe enrolled N = 39 participants (n = 19 TDF-FTC, n = 20 TAF-FTC): median age was 28 years (IQR:25–34); median gestational age was 24-weeks (IQR:21–28). For TDF-FTC, TFV-DP DBS concentrations at 8-weeks did not differ significantly between pregnancy (GM: 675; 95%CI:537–849) and postpartum (GM: 583; 95%CI:471–722; GMR-TDF = 1.16; 95%CI:0.74–1.80). For TAF-FTC, TFV-DP DBS concentrations at 8-weeks were 44% higher in postpartum (GM: 1199; 95%CI:929–1549) versus pregnancy (GM: 832; 95%CI:751–922; GMR-TAF = 1.44; 95% CI: 1.01–2.06). In PBMC analysis of TDF-FTC, 8-week median TFV-DP (pmol/10^6 cell) was 71 (IQR 44–112) in pregnancy and 73 (IQR 50–102) in postpartum (GMR = 1.04; 95%CI:0.44–2.44). In TAF-FTC, median PBMC at 8-weeks was 580 (IQR:341–985) in pregnancy and 666 (IQR:396–1123) in postpartum (GMR = 1.15; 95%CI:0.30–2.49). ConclusionTFV-DP concentrations were overall lower during pregnancy than postpartum for TAF-FTC. We found high concentrations of TFV-DP in PBMC in pregnancy and postpartum on TAF-FTC, suggesting PrEP efficacy is maintained. Efficacy and safety studies are warranted to evaluate TAF-FTC for PrEP in pregnant and postpartum women.