Assuntos
Fármacos Anti-HIV , Farmacorresistência Viral , Infecções por HIV , Adulto , Humanos , Adenina/análogos & derivados , Adenina/uso terapêutico , Fármacos Anti-HIV/uso terapêutico , Negro ou Afro-Americano , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Combinação de Medicamentos , Emtricitabina/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Adesão à Medicação/estatística & dados numéricos , Piperazinas/uso terapêutico , Piridonas/uso terapêutico , Tenofovir/uso terapêutico , Tenofovir/análogos & derivados , Resultado do Tratamento , Estados UnidosRESUMO
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.
Assuntos
Antivirais , Hepatite B Crônica , Tenofovir , Carga Viral , Humanos , Tenofovir/uso terapêutico , Tenofovir/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Hepatite B Crônica/sangue , Masculino , Feminino , Carga Viral/efeitos dos fármacos , Estudos Retrospectivos , Antivirais/uso terapêutico , Antivirais/efeitos adversos , Antivirais/farmacologia , Adulto , Pessoa de Meia-Idade , Resultado do Tratamento , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/genética , Alanina/análogos & derivados , Alanina/uso terapêutico , Adenina/análogos & derivados , Adenina/uso terapêutico , Adenina/efeitos adversos , DNA Viral/sangueRESUMO
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.
Assuntos
Fármacos Anti-HIV , Dislipidemias , Infecções por HIV , Tenofovir , Humanos , Infecções por HIV/tratamento farmacológico , Tenofovir/uso terapêutico , Tenofovir/efeitos adversos , Tenofovir/análogos & derivados , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Dislipidemias/induzido quimicamente , Alanina/uso terapêutico , Fatores de Risco , Masculino , Aminobutiratos/efeitos adversos , Aminobutiratos/uso terapêutico , Feminino , Adenina/análogos & derivados , Adenina/uso terapêutico , Adenina/efeitos adversosRESUMO
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.
Assuntos
Alanina , Antivirais , Hepatite B Crônica , Lipídeos , Tenofovir , Humanos , Tenofovir/uso terapêutico , Tenofovir/análogos & derivados , Masculino , Feminino , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/sangue , Hepatite B Crônica/virologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Antivirais/uso terapêutico , Alanina/uso terapêutico , Lipídeos/sangue , Dislipidemias/sangue , Dislipidemias/tratamento farmacológico , Dislipidemias/induzido quimicamente , Adenina/análogos & derivados , Adenina/uso terapêutico , Triglicerídeos/sangue , Colesterol/sangueRESUMO
BACKGROUND: Head-to-head data for bictegravir/emtricitabine/tenofovir alafenamide (BIC/F/TAF; B) and darunavir/cobicistat/emtricitabine/tenofovir alafenamide (DRV/c/F/TAF; D) are lacking in the context of rapid antiretroviral therapy (ART) initiation. This study, BIC-T&T, evaluates the efficacy and tolerability of B vs D in a UK test-and-treat setting. SETTING: BIC-T&T was a randomised, open-label, multi-centre, study in which participants initiated ART within 14 days after confirmed HIV-1 diagnosis before baseline laboratory. METHODS: The primary endpoint is the virological response (HIV RNA < 50copies/mL) at week 12 by time-weighted average change in log10 HIV RNA recorded in viral load assays from treatment initiation to week 12, using two-sample Wilcoxon rank-sum test. RESULTS: 36 participants were randomised: 94% were male, 53% white; mean (SD) age was 35 years (11.8). Baseline mean (±SD) log10 HIV-RNA was 4.79 (± 0.87) log10 copies/mL and CD4 505 (±253) cells/mm3. The mean (±SD) time from confirmed HIV diagnosis to ART initiation was 7.9 (± 3.7) days. The time-weighted mean decrease in log10 HIV RNA from treatment initiation to week 12 was significantly greater in B in comparison to D (3.1 vs. 2.6 log10 copies/mL, p < 0.001). Both regimens demonstrated good tolerability with infrequent laboratory abnormalities and no grade 3 or 4 adverse events. CONCLUSION: In this first head-to-head study in the context of ART initiation, HIV RNA decline from baseline to week 12 was significantly more rapid for BIC/F/TAF compared with DRV/c/F/TAF.
Assuntos
Fármacos Anti-HIV , Emtricitabina , Infecções por HIV , Tenofovir , Carga Viral , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Masculino , Feminino , Adulto , Tenofovir/uso terapêutico , Tenofovir/análogos & derivados , Fármacos Anti-HIV/uso terapêutico , Carga Viral/efeitos dos fármacos , Emtricitabina/uso terapêutico , HIV-1/efeitos dos fármacos , HIV-1/genética , Adenina/análogos & derivados , Adenina/uso terapêutico , Piperazinas/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Darunavir/uso terapêutico , Alanina/uso terapêutico , Alanina/análogos & derivados , Resultado do Tratamento , RNA Viral , Sulfonamidas/uso terapêutico , Pessoa de Meia-Idade , Cobicistat/uso terapêutico , Reino Unido , Combinação de Medicamentos , Amidas , PiridonasRESUMO
This letter to the editor relates to the study entitled "Tenofovir amibufenamide vs tenofovir alafenamide for treating chronic hepatitis B: A real-world study", which was recently published by Peng et al. Hepatitis B virus infection represents a significant health burden worldwide and can lead to cirrhosis and even liver cancer. The antiviral drugs currently used to treat patients with chronic hepatitis B infection still have many side effects, so it is crucial to identify safe and effective drugs to inhibit viral replication.
Assuntos
Antivirais , Vírus da Hepatite B , Hepatite B Crônica , Tenofovir , Humanos , Antivirais/uso terapêutico , Antivirais/efeitos adversos , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Tenofovir/uso terapêutico , Tenofovir/análogos & derivados , Tenofovir/efeitos adversos , Vírus da Hepatite B/efeitos dos fármacos , Resultado do Tratamento , Replicação Viral/efeitos dos fármacos , Adenina/análogos & derivados , Adenina/uso terapêutico , Adenina/efeitos adversos , Alanina/análogos & derivados , Alanina/uso terapêutico , Alanina/efeitos adversosRESUMO
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.
Assuntos
Antivirais , Quimioterapia Combinada , Hepatite B Crônica , Interferon-alfa , Polietilenoglicóis , Proteínas Recombinantes , Tenofovir , Humanos , Tenofovir/uso terapêutico , Tenofovir/administração & dosagem , Tenofovir/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Masculino , Feminino , Antivirais/uso terapêutico , Antivirais/efeitos adversos , Antivirais/administração & dosagem , Criança , Proteínas Recombinantes/uso terapêutico , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Polietilenoglicóis/uso terapêutico , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/administração & dosagem , Interferon-alfa/uso terapêutico , Interferon-alfa/administração & dosagem , Interferon-alfa/efeitos adversos , Pré-Escolar , Resultado do Tratamento , Interferon alfa-2/uso terapêutico , Interferon alfa-2/administração & dosagem , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/efeitos dos fármacos , DNA Viral/sangue , Alanina/uso terapêutico , Alanina/análogos & derivadosRESUMO
OBJECTIVES: To determine the metabolic effects of tenofovir alafenamide (TAF) compared to tenofovir disoproxil fumarate (TDF) in vivo . DESIGN AND METHODS: Male Wistar rats ( Rattus novergicus , 250-300âg body weight) were divided into three groups ( n â=â8) and orally treated daily with 1.0âml distilled water (group 1), TAF (0.42âmg/kg) (group 2), or TDF (5.0âmg/kg) (group 3), respectively, for 56âdays. 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). RESULTS: 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. CONCLUSIONS: TAF treatment is weight-neutral and causes dysglycemia, and dyslipidemia but not Fanconi syndrome compared to TDF.
Assuntos
Adenina , Dislipidemias , Ratos Wistar , Tenofovir , Animais , Tenofovir/análogos & derivados , Masculino , Dislipidemias/induzido quimicamente , Adenina/análogos & derivados , Adenina/efeitos adversos , Adenina/farmacologia , Ratos , Alanina , Fármacos Anti-HIV , Teste de Tolerância a Glucose , Glicemia/análise , Rim/efeitos dos fármacos , Pâncreas/efeitos dos fármacos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Estresse Oxidativo/efeitos dos fármacosAssuntos
Alanina , Fármacos Anti-HIV , Infecções por HIV , Piridonas , Rilpivirina , Tenofovir , Humanos , Infecções por HIV/tratamento farmacológico , Rilpivirina/uso terapêutico , Fármacos Anti-HIV/uso terapêutico , Piridonas/uso terapêutico , Tenofovir/uso terapêutico , Tenofovir/análogos & derivados , Alanina/uso terapêutico , Alanina/administração & dosagem , Masculino , Pessoa de Meia-Idade , HDL-Colesterol/sangue , Feminino , Piridinas/uso terapêutico , Adenina/análogos & derivados , Adenina/uso terapêutico , Adenina/administração & dosagem , Resultado do Tratamento , Adulto , Substituição de Medicamentos , DicetopiperazinasRESUMO
Many acyclic nucleoside phosphonates such as cidofovir, adefovir dipivoxil, tenofovir disoproxil fumarate, and tenofovir alafenamide have been marketed for the treatment or prophylaxis of infectious diseases. Here, this review highlights potent acyclic nucleoside phosphonates for their potential in the treatment of retrovirus (e.g., human immunodeficiency virus) and DNA virus (e.g., adeno-, papilloma-, herpes- and poxvirus) infections. If properly assessed and/or optimized, some potent acyclic nucleoside phosphonates can be possibly applied in the control of current and emerging infectious diseases.
Assuntos
Antivirais , Organofosfonatos , Humanos , Organofosfonatos/química , Organofosfonatos/farmacologia , Antivirais/farmacologia , Antivirais/química , Animais , Nucleosídeos/química , Nucleosídeos/farmacologia , Viroses/tratamento farmacológico , Adenina/análogos & derivados , Adenina/química , Adenina/farmacologia , Tenofovir/análogos & derivadosAssuntos
Fármacos Anti-HIV , Infecções por HIV , Complicações Infecciosas na Gravidez , Terceiro Trimestre da Gravidez , Viremia , Humanos , Gravidez , Adenina/administração & dosagem , Adenina/efeitos adversos , Adenina/análogos & derivados , Alanina/administração & dosagem , Alanina/efeitos adversos , Amidas , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Emtricitabina/administração & dosagem , Emtricitabina/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos , Infecções por HIV/sangue , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Piperazinas/administração & dosagem , Piperazinas/efeitos adversos , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/virologia , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Tenofovir/administração & dosagem , Tenofovir/efeitos adversos , Tenofovir/análogos & derivados , Viremia/sangue , Viremia/diagnóstico , Viremia/tratamento farmacológico , Viremia/virologiaRESUMO
AIMS: Trans/transfeminine women are disproportionally affected by HIV. Concerns regarding negative drug-drug interactions (DDIs) between ART drugs and gender-affirming hormone therapy (GAHT), specifically feminizing hormone therapy (FHT), may contribute to the lower ART uptake by trans women with HIV compared with their cis counterparts. The aim of this study is to investigate the bidirectional pharmacokinetic effects of components of FHT regimens (oral oestradiol and androgen-suppressing medications) with the ART regimen (bictegravir/emtricitabine/tenofovir alafenamide [B/F/TAF)]. METHODS: We present a protocol for a three-armed, parallel-group, longitudinal (6-month), DDI study. Group 1 includes 15 3trans women with HIV taking FHT and ART; group 2 includes 15 premenopausal cis women with HIV taking ART; group 3 includes 15 trans women without HIV taking FHT. Women with HIV must be on or switch to B/F/TAF at baseline and be virally suppressed for ≥3 months. Trans women must be taking a stable regimen of ≥2 mg daily oral oestradiol and an anti-androgen (pharmaceutical, and/or surgical, and/or medical) for ≥3 months. Plasma ART drug concentrations will be sampled at Month 2 and compared between groups 1 and 2. Serum oestradiol concentrations will be sampled at baseline and Month 2 visits and compared between groups 1 and 3. The primary outcomes are B/F/TAF pharmacokinetic parameters (Cmin, Cmax and AUC) and oestradiol concentrations (Cmin, C4h, Cmax and AUC) at month 2. DISCUSSION: This study is of global importance as it provides critical information regarding safe coadministration of B/F/TAF and FHT, both of which are life-saving therapies for trans women with HIV.
Assuntos
Adenina , Fármacos Anti-HIV , Interações Medicamentosas , Emtricitabina , Estradiol , Infecções por HIV , Piperazinas , Tenofovir , Pessoas Transgênero , Humanos , Feminino , Infecções por HIV/tratamento farmacológico , Emtricitabina/farmacocinética , Emtricitabina/administração & dosagem , Tenofovir/farmacocinética , Tenofovir/administração & dosagem , Tenofovir/análogos & derivados , Fármacos Anti-HIV/farmacocinética , Fármacos Anti-HIV/administração & dosagem , Estradiol/administração & dosagem , Estradiol/sangue , Estradiol/farmacocinética , Piperazinas/administração & dosagem , Piperazinas/farmacocinética , Adulto , Adenina/análogos & derivados , Adenina/farmacocinética , Adenina/administração & dosagem , Compostos Heterocíclicos de 4 ou mais Anéis/farmacocinética , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Alanina/farmacocinética , Alanina/administração & dosagem , Piridonas/administração & dosagem , Piridonas/farmacocinética , Estudos Longitudinais , Combinação de Medicamentos , Antagonistas de Androgênios/farmacocinética , Antagonistas de Androgênios/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/farmacocinética , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Pessoa de Meia-Idade , Adulto Jovem , Amidas/farmacocinética , Amidas/administração & dosagemRESUMO
INTRODUCTION: Rapid initiation of ART after HIV diagnosis is recommended for individual and public health benefits. However, certain clinical and ART-related considerations hinder immediate initiation of therapy. METHODS: An open-label, single-arm, single-centre 48-week prospective clinical trial involving ART-naïve HIV-diagnosed adults who started bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) within a week from the first hospital visit, before the availability of baseline laboratory and genotype results. The primary aim was to determine the proportion of people with at least one condition that would hinder immediate initiation of any recommended ART regimen other than BIC/FTC/TAF. Clinicaltrials.gov: NCT04416906. RESULTS: We included 100 participants: 79% men, 64% from Latin America, median age 32 years. According to European AIDS Clinical Society (EACS) and US Department of Health and Human Services 2023 guidelines, 11% (95%CI 6; 19) of participants had at least one condition that made any ART different from BIC/FTC/TAF less appropriate for a rapid ART strategy. Seventy-nine percent of the people started BIC/FTC/TAF within the first 48 hours of their first hospital visit. There were 16 early discontinuations (11 lost to follow-up). By week 48, 92% (95%CI 86; 98) of the participants of the ITT population with observed data achieved viral suppression. Eight grade 3-4 adverse events (AEs), five serious AEs and six ART-related AEs were identified. Adherence remained high. CONCLUSIONS: BIC/FTC/TAF is an optimal treatment for rapid initiation of ART. However, additional strategies to improve retention in care must be implemented.
Assuntos
Alanina , Fármacos Anti-HIV , Emtricitabina , Infecções por HIV , Piridonas , Tenofovir , Humanos , Infecções por HIV/tratamento farmacológico , Masculino , Adulto , Estudos Prospectivos , Feminino , Tenofovir/uso terapêutico , Tenofovir/administração & dosagem , Tenofovir/análogos & derivados , Emtricitabina/uso terapêutico , Emtricitabina/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/administração & dosagem , Piridonas/administração & dosagem , Alanina/uso terapêutico , Alanina/administração & dosagem , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos , Piperazinas/administração & dosagem , Amidas/administração & dosagem , Amidas/uso terapêutico , Adenina/análogos & derivados , Adenina/uso terapêutico , Adenina/administração & dosagem , Adenina/efeitos adversos , Combinação de Medicamentos , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Pessoa de Meia-Idade , Adulto Jovem , Carga Viral/efeitos dos fármacosRESUMO
BACKGROUND: The ongoing, observational BICSTaR (BICtegravir Single Tablet Regimen) cohort study is evaluating real-world effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in people with HIV across 14 countries over 24 months. We present 12-month data from the BICSTaR Asia cohort. METHODS: Data were pooled from retrospective and prospective cohorts of antiretroviral therapy (ART)-naïve (hereafter, TN) and ART-experienced (hereafter, TE) people with HIV (aged ≥21 years) receiving B/F/TAF in routine clinical care in the Republic of Korea, Singapore, and Taiwan. Analyses included effectiveness (primary endpoint: HIV-1 RNA <50 copies/ml, missing = excluded analysis), CD4 count, CD4/CD8 ratio, safety, treatment persistence, and patient-reported outcomes (prospective group). RESULTS: The analysis population included 328 participants (80 retrospective, 248 prospective; 65 TN, 263 TE). Participants were predominantly male (96.9% TN, 93.2% TE) with ≥1 comorbidity (52.3% TN, 57.8% TE); median age (years) was 31 (TN) and 42 (TE). Following 12 months of B/F/TAF, HIV-1 RNA was <50 copies/ml in 98.2% (54/55) of TN and 97.0% (227/234) of TE participants. Median (Q1, Q3) CD4 cell count increased by +187 (119, 291) cells/µl in the TN group (p < 0.001) and remained stable (+8 [-91, 110] cells/µl) in the TE group. B/F/TAF persistence was high in the prospective group, with 1/34 (2.9%) TN and 5/214 (2.3%) TE participants discontinuing treatment within 12 months. Drug-related adverse events occurred in 5.8% (19/328) of participants, leading to treatment discontinuation in 0.6% (2/328). CONCLUSIONS: Real-world evidence from BICSTaR supports the effectiveness, safety and tolerability of B/F/TAF in people with HIV in Asia.
Assuntos
Fármacos Anti-HIV , Emtricitabina , Infecções por HIV , HIV-1 , Piridonas , Tenofovir , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Masculino , Feminino , Adulto , Tenofovir/uso terapêutico , Tenofovir/análogos & derivados , Emtricitabina/uso terapêutico , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Estudos Retrospectivos , Pessoa de Meia-Idade , Estudos Prospectivos , Piridonas/uso terapêutico , Resultado do Tratamento , Contagem de Linfócito CD4 , HIV-1/efeitos dos fármacos , HIV-1/genética , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos , Piperazinas/uso terapêutico , Adenina/análogos & derivados , Adenina/uso terapêutico , Adenina/efeitos adversos , Alanina/uso terapêutico , Alanina/análogos & derivados , Combinação de Medicamentos , Carga Viral/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Singapura/epidemiologia , Amidas/uso terapêutico , Taiwan , Estudos de Coortes , RNA Viral/sangueRESUMO
INTRODUCTION: Recent evidence has raised questions about whether newer HIV treatment regimens, including dolutegravir (DTG) and tenofovir alafenamide (TAF), are associated with increases in blood pressure (BP). METHODS: We assessed changes in BP by treatment regimen and evaluated the relative contribution of kidney function and weight gain to these changes among participants in the ADVANCE phase-3 trial clinical trial in South Africa (study dates: January 2017-February 2022). Our primary outcome of interest was a change in systolic BP (SBP) at 96 and 192 weeks, among those not receiving antihypertensive medication. The secondary outcome was treatment-emergent hypertension at these same time points, defined as BP ≥140/90 mmHg on two occasions, or initiation of antihypertensive medication after week 4 among individuals without hypertension at enrolment. We used linear regression to evaluate the relationship between change in estimated glomerular filtration rate (eGFR) and change in SBP; and Poisson regression to evaluate the relationship between change in eGFR and treatment-emergent hypertension at each time point. All models were adjusted for age, sex, treatment group and change in body mass index (BMI). RESULTS: Over 96 weeks, the average changes in SBP were 1.7 mmHg (95% CI: 0.0-3.4), -0.5 mmHg (95% CI: -2.2 to 1.7) and -2.1 mmHg (95% CI: -3.8 to 0.4) in the TAF/emtricitabine (FTC)/DTG, tenofovir disoproxil fumarate (TDF)/FTC/DTG and TDF/FTC/efavirenz (EFV) groups, respectively. This difference was significant for the TAF/FTC/DTG compared to the TDF/FTC/EFV group (p = 0.002). Over 96 weeks, 18.2% (95% CI: 13.4-22.9), 15.4% (95% CI: 11.0-19.9) and 13.3% (95% CI: 8.9-17.6) of participants developed treatment-emergent hypertension, respectively. In adjusted models, there was no significant relationship between change in eGFR and either outcome. Change in BMI was significantly associated with an increase in SBP, while age was associated with an increased risk of treatment-emergent hypertension. Adjustment for BMI also mitigated the unadjusted relationship between HIV treatment regimen and SBP where present. CONCLUSIONS: In the ADVANCE cohort, weight gain and age accounted for increases in BP and risk of treatment-emergent hypertension. HIV treatment programmes may need to integrate the management of obesity and hypertension into routine care. CLINICAL TRIAL NUMBER: NCT03122262.
Assuntos
Pressão Sanguínea , Infecções por HIV , Hipertensão , Tenofovir , Aumento de Peso , Humanos , Masculino , Feminino , África do Sul , Infecções por HIV/tratamento farmacológico , Adulto , Pessoa de Meia-Idade , Tenofovir/uso terapêutico , Tenofovir/efeitos adversos , Tenofovir/análogos & derivados , Aumento de Peso/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Piridonas/uso terapêutico , Piperazinas/uso terapêutico , Oxazinas/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Taxa de Filtração Glomerular/efeitos dos fármacos , Alanina/uso terapêutico , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/efeitos adversosRESUMO
BACKGROUND: The rapid start of antiretroviral therapy (RSA) model initiates antiretroviral therapy (ART) as soon as possible after a new or preliminary diagnosis of HIV, in advance of HIV-1 RNA and other baseline laboratory testing. This observational study aims to determine if RSA with a single tablet regimen of bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF) is an effective regimen for achieving viral suppression and accepted by patients at the time of diagnosis. METHODS: Adults newly or preliminarily diagnosed with HIV were enrolled from October 2018 through September 2021. Real world advantage, measured in days between clinical milestones and time to virologic suppression, associated with B/F/TAF RSA was compared to historical controls. RESULTS: All Study RSA participants (n = 45) accepted treatment at their first visit and 43(95.6%) achieved virologic suppression by week 48. Study RSA participants had a significantly shorter time (median 32 days) from diagnosis to ART initiation and virologic suppression, in comparison to historical controls (median 181 days) (n = 42). Qualitative feedback from study RSA participants showed high acceptance positive response to RSA. CONCLUSIONS: RSA is feasible and well accepted by patients in a real-world community-based clinic setting. Promoting RSA in community-based clinics is an important tool in ending the HIV epidemic.
Assuntos
Fármacos Anti-HIV , Emtricitabina , Infecções por HIV , Tenofovir , Humanos , Infecções por HIV/tratamento farmacológico , Projetos Piloto , Masculino , Feminino , Adulto , Tenofovir/uso terapêutico , Tenofovir/administração & dosagem , Tenofovir/análogos & derivados , Pessoa de Meia-Idade , Fármacos Anti-HIV/uso terapêutico , Emtricitabina/uso terapêutico , Emtricitabina/administração & dosagem , Alanina/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , HIV-1/efeitos dos fármacos , Piperazinas/uso terapêutico , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Carga Viral/efeitos dos fármacos , Amidas/uso terapêutico , RNA Viral/sangue , PiridonasRESUMO
A lack of adherence to long-term antiretroviral therapy may impact viral suppression. The current study examined the relationship between medication adherence and clinical outcomes in people with human immunodeficiency virus infection (PWH) receiving bictegravir, emtricitabine, and tenofovir alafenamide fumarate (B/F/TAF). A retrospective cohort study using two Japanese claims databases was conducted. Adherence was measured by the proportion of days covered (PDC). Patients were grouped into 3 PDC category and persistence was estimated by Kaplan-Meier method. Cox regression analysis was performed to investigate whether the PDC was associated with treatment discontinuation. Among 952 patients, 820 (86.1%), 95 (10.0%), and 37 (3.9%) patients were grouped into the PDC ≥ 90%, 80- < 90%, and < 80% groups, respectively. Across all PDC groups, more than 90% of patients who received B/F/TAF were receiving treatment at 1 year. There was no significant difference in the risk of discontinuation between the lower PDC groups (80- < 90% and < 80%) and the PDC ≥ 90% group (0.400 [0.096, 1.661]; 2.244 [0.663, 7.594], hazard ratio [95% confidence interval], respectively). A drug resistance test was implemented for 15 patients, none of whom discontinued B/F/TAF after the test. The results suggest that events that could cause discontinuation, such as virologic failure, were not associated with PDC.
Assuntos
Alanina , Fármacos Anti-HIV , Emtricitabina , Infecções por HIV , Adesão à Medicação , Piridonas , Tenofovir , Humanos , Tenofovir/uso terapêutico , Tenofovir/análogos & derivados , Masculino , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Emtricitabina/uso terapêutico , Japão , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Fármacos Anti-HIV/uso terapêutico , Alanina/uso terapêutico , Alanina/análogos & derivados , Piridonas/uso terapêutico , Piperazinas/uso terapêutico , Resultado do Tratamento , Amidas/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Adenina/análogos & derivados , Adenina/uso terapêutico , Bases de Dados Factuais , Combinação de MedicamentosRESUMO
BACKGROUND: Data characterising the long-term use and safety of emtricitabine plus tenofovir disoproxil fumarate as daily oral pre-exposure prophylaxis (PrEP) are scarce and there are uncertainties regarding the value of routine HIV-1 RNA testing during oral PrEP follow-up. METHODS: The DISCOVER trial was a randomised, controlled, phase 3 trial in which cisgender men and transgender women aged 18 years and older with a high likelihood of acquiring HIV were recruited from 94 clinics in Europe and North America and randomly assigned to receive either emtricitabine plus tenofovir disoproxil fumarate (200/25 mg) tablets daily, with matched placebo tablets, or emtricitabine plus tenofovir alafenamide (200/300 mg) tablets daily, with matched placebo tablets, for at least 96 weeks. After completion of the trial, participants were offered enrolment in this 48-week open-label extension study of emtricitabine plus tenofovir alafenamide. In participants diagnosed with HIV during the randomised and open-label phases of the study, we characterised HIV-1 test results and measured HIV-1 RNA viral load retrospectively when available. Adherence based on tenofovir diphosphate concentrations in dried blood spots and genotypic resistance were assessed in participants diagnosed with HIV. Safety assessments included adverse events, laboratory parameters, and, in a subset of participants, bone mineral density. HIV-1 incidence in participants initially randomly assigned to receive emtricitabine plus tenofovir alafenamide was estimated using a Poisson distribution. Changes from baseline in safety endpoints were described in participants assigned to received emtricitabine plus tenofovir alafenamide and in those who switched from emtricitabine plus tenofovir disoproxil fumarate during the open-label phase. This trial is registered with ClinicalTrials.gov, NCT02842086, and is ongoing. FINDINGS: Between Sept 13, 2016, and June 30, 2017, 5399 participants were enrolled and randomly assigned in DISCOVER. 2699 were assigned to receive emtricitabine plus tenofovir disoproxil fumarate and 2700 were assigned to receive emtricitabine plus tenofovir alafenamide, of whom 2693 and 2694, respectively, received at least one dose of study drug. 2115 (79%) assigned to emtricitabine plus tenofovir disoproxil fumarate switched to emtricitabine plus tenofovir alafenamide in the open-label phase, and 2070 (77%) continued with emtricitabine plus tenofovir alafenamide in the open-label phase. As of data cutoff (Dec 10, 2020), after 15 817 person-years of follow-up, 27 new HIV-1 diagnoses were observed across the total study period, with three occurring during the open-label phase. In participants who were initially assigned to emtricitabine plus tenofovir alafenamide, the incidence was 0·13 per 100 person-years (95% CI 0·061-0·23; ten of 2670). Stored plasma samples were available for 23 of 27 participants, including 22 with incident infection. In four (17%) of 23 participants, retrospective testing detected HIV-1 RNA before serological HIV-1 test positivity; one was a suspected baseline infection. Of the three incident cases, all three were non-adherent to PrEP and none developed drug resistance. Among participants taking emtricitabine plus tenofovir alafenamide for up to 144 weeks, markers of glomerular filtration and proximal renal tubule dysfunction (ß2-microglobulin to creatinine ratio and retinol-binding protein to creatinine ratio) improved or remained stable at 144 weeks compared with baseline, bone mineral density in hip and lumbar spine increased or remained stable from baseline to week 144 (n=191), cholesterol and glucose concentrations remained stable, and median bodyweight increased by less than 1 kg per year. In participants who switched from emtricitabine plus tenofovir disoproxil fumarate during the open-label phase (2115 [79%] of 2693), markers of glomerular filtration and proximal renal tubule dysfunction improved or remained stable, bone mineral density increased, cholesterol concentrations increased, glucose concentrations were similar, and median bodyweight increased more compared with those who remained on emtricitabine and tenofovir alafenamide. INTERPRETATION: Routine HIV-1 RNA testing for follow-up of individuals on daily oral PrEP provides modest additional clinical benefit. Long-term use of emtricitabine and tenofovir alafenamide as daily oral PrEP is safe and well tolerated and can be an especially appropriate choice for people with bone or renal morbidities. FUNDING: Gilead Sciences.
Assuntos
Adenina , Alanina , Fármacos Anti-HIV , Emtricitabina , Infecções por HIV , HIV-1 , Profilaxia Pré-Exposição , Tenofovir , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Infecções por HIV/prevenção & controle , Masculino , Tenofovir/administração & dosagem , Tenofovir/efeitos adversos , Tenofovir/análogos & derivados , Feminino , Profilaxia Pré-Exposição/métodos , Emtricitabina/administração & dosagem , Emtricitabina/efeitos adversos , Emtricitabina/uso terapêutico , HIV-1/efeitos dos fármacos , HIV-1/genética , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Alanina/administração & dosagem , Adenina/análogos & derivados , Adenina/administração & dosagem , Adenina/efeitos adversos , Adenina/uso terapêutico , Farmacorresistência Viral , Pessoa de Meia-Idade , Carga Viral/efeitos dos fármacos , Adulto Jovem , RNA Viral/sangue , Europa (Continente)/epidemiologiaRESUMO
INTRODUCTION: The amino acid substitution A62V in reverse transcriptase was identified as a mutation correlated with virologic failure in patients on first-line therapy including tenofovir (TDF) and tenofovir alafenamide (TAF). A62V is a typically polymorphic mutation in HIV-1 sub-subtype A6, which is the most widespread virus variant in Russia. MATERIALS AND METHODS: The European EuResist (EIDB) database was queried to form two equivalent groups of patients: group 1 â patients with A62V at baseline treated with TDF or TAF on the first-line therapy, group 2 â patients without A62V at baseline treated with TDF or TAF on the first-line therapy. Each group included 23 patients. RESULTS: There was no statistical difference between the two groups in virologic efficacy in 4, 12, and 24 weeks after the start of antiretroviral therapy (ART) and in the frequency of virologic failures. CONCLUSION: This study has some limitations, and the exact role of A62V in the efficacy of the first-line ART based on tenofovir deserves further investigation.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Transcriptase Reversa do HIV , HIV-1 , Mutação , Tenofovir , Humanos , Tenofovir/uso terapêutico , Tenofovir/análogos & derivados , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Infecções por HIV/genética , Transcriptase Reversa do HIV/genética , HIV-1/genética , HIV-1/efeitos dos fármacos , Masculino , Feminino , Adulto , Fármacos Anti-HIV/uso terapêutico , Pessoa de Meia-Idade , Farmacorresistência Viral/genética , Substituição de Aminoácidos , Alanina/uso terapêutico , Federação Russa/epidemiologia , Adenina/análogos & derivados , Adenina/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Carga Viral/efeitos dos fármacosRESUMO
BACKGROUND: Phase 3 studies in patients with chronic hepatitis B have shown tenofovir alafenamide to have non-inferior efficacy to tenofovir disoproxil fumarate, with improved renal and bone safety. We conducted this study to evaluate the safety and efficacy of switching to tenofovir alafenamide in participants with chronic hepatitis B and renal or hepatic impairment. METHODS: This open-label, multicentre, phase 2 study was done in eight countries or territories at 30 sites. We recruited adults (≥18 years) with chronic hepatitis B who were virally suppressed on nucleoside or nucleotide analogues and had renal impairment (part A: moderate or severe in cohort 1 [estimated glomerular filtration rate by the Cockcroft-Gault formula (eGFRCG) 15-59 mL/min] or end-stage renal disease [eGFRCG <15 mL/min] on haemodialysis in cohort 2) or hepatic impairment including decompensation (part B: Child-Turcotte-Pugh score 7-12). Participants switched to 25 mg of tenofovir alafenamide given orally once daily for 96 weeks. The primary endpoint was the proportion of participants with viral suppression (HBV DNA <20 IU/mL) at week 24 by missing-equals-failure analysis. Efficacy (full analysis set) and safety (safety analysis set) analyses included all enrolled participants who received at least one dose of the study drug. Week 96 safety was assessed, including renal and bone parameters. This trial is registered at ClinicalTrials.gov, NCT03180619, and is completed. FINDINGS: 124 participants (93 in part A [78 in cohort 1 and 15 in cohort 2] and 31 in part B) were enrolled between Aug 11, 2017, and Oct 17, 2018, and included in the full and safety analysis sets. 106 (85%) participants completed the study. There were 69 (74%) men and 24 (26%) women in part A and 21 (68%) men and ten (32%) women in part B. At week 24, 91 (97·8%, 95% CI 92·4 to 99·7) of 93 individuals in part A (76 [97·4%, 91·0 to 99·7] of 78 in cohort 1 and 15 [100·0%, 78·2 to 100·0] of 15 in cohort 2) and 31 (100·0%, 88·8 to 100·0) in part B had HBV DNA of less than 20 IU/mL. By week 96, the most common adverse event was upper respiratory tract infection, which occurred in 14 (15%) participants in part A and in six (19%) participants in part B. Serious adverse events occurred in 20 (22%) part A participants and in ten (32%) part B participants; none were related to treatment. No treatment-related deaths occurred. At week 96, median change in estimated glomerular filtration rate (Cockcroft-Gault method) was 1·0 mL/min (IQR -2·8 to 4·5) in cohort 1 and -2·4 mL/min (-11·4 to 10·7) in part B. Mean changes in spine and hip bone mineral density were 1·02% (SD 4·44) and 0·20% (3·25) in part A and -0·25% (3·91) and 0·28% (3·25) in part B. INTERPRETATION: Tenofovir alafenamide might offer continued antiviral efficacy and a favourable safety profile for patients with renal or hepatic impairment and chronic hepatitis B switching from tenofovir disoproxil fumarate or other antivirals. FUNDING: Gilead Sciences.