RESUMEN
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.
Asunto(s)
Antivirales , Virus de la Hepatitis B , Hepatitis B Crónica , Tenofovir , Humanos , Antivirales/uso terapéutico , Antivirales/efectos adversos , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/virología , Tenofovir/uso terapéutico , Tenofovir/análogos & derivados , Tenofovir/efectos adversos , Virus de la Hepatitis B/efectos de los fármacos , Resultado del Tratamiento , Replicación Viral/efectos de los fármacos , Adenina/análogos & derivados , Adenina/uso terapéutico , Adenina/efectos adversos , Alanina/análogos & derivados , Alanina/uso terapéutico , Alanina/efectos adversosRESUMEN
BACKGROUND: There have been reports of serious side effects of Remdesivir, including cardiovascular complications. The present study aimed to determine the adverse cardiovascular effects of Remdesivir and the factors affecting them in COVID-19 patients. METHODS: The patients were classified into two groups: those receiving Remdesivir without cardiac complications and those receiving Remdesivir with cardiovascular complications. After reviewing the patient's medical records, the relationship of some factors with the incidence of adverse cardiovascular effects was measured. RESULTS: Chi-square test showed that the distribution of complications in men was significantly higher than in women (P=0.001). The independent t-test revealed that the mean age in the group with complications was significantly higher than the group without complications (P=0.013). Fisher's exact test demonstrated a significant relationship between smoking and cardiovascular complications (P=0.05). According to the Mann-Whitney test, a significant difference was found in the mean changes of Bilirubin (P=0.02) and ALKP (P=0.01) before and after treatment in the groups with and without heart complications. CONCLUSION: Our findings indicated that most of the COVID-19 patients suffered from sinus bradycardia, and the distribution of complications was more pronounced in men than in women. The mean age in the group with complications was higher than the group without complications. Smoking was found to be associated with the occurrence of cardiovascular complications and the mean changes of Bilirubin and ALKP before and after treatment were significantly different in the groups with and without cardiovascular complications.
Asunto(s)
Adenosina Monofosfato , Alanina , Antivirales , Tratamiento Farmacológico de COVID-19 , COVID-19 , Humanos , Masculino , Alanina/análogos & derivados , Alanina/efectos adversos , Alanina/uso terapéutico , Femenino , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/efectos adversos , Adenosina Monofosfato/uso terapéutico , Persona de Mediana Edad , Antivirales/efectos adversos , Antivirales/uso terapéutico , Estudios de Casos y Controles , Anciano , COVID-19/complicaciones , Adulto , SARS-CoV-2 , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/epidemiología , Factores Sexuales , Bradicardia/inducido químicamente , Bradicardia/epidemiología , Estudios RetrospectivosRESUMEN
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.
Asunto(s)
Adenina , Alanina , Antivirales , Hepatitis B Crónica , Tenofovir , Humanos , Masculino , Femenino , Tenofovir/uso terapéutico , Tenofovir/efectos adversos , Tenofovir/análogos & derivados , Hepatitis B Crónica/tratamiento farmacológico , Persona de Mediana Edad , Alanina/uso terapéutico , Alanina/efectos adversos , Antivirales/uso terapéutico , Antivirales/efectos adversos , Adulto , Adenina/análogos & derivados , Adenina/uso terapéutico , Adenina/efectos adversos , Sustitución de Medicamentos , Anciano , Resultado del Tratamiento , Tasa de Filtración Glomerular/efectos de los fármacosRESUMEN
(1) Background: Geriatric patients are at high risk of complications of Coronavirus disease-2019 (COVID-19) and are good candidates for antiviral drugs. (2) Methods: A retrospective study of electronic health records (EHRs) aiming to describe antiviral (nirmatrelvir and ritonavir (nirmatrelvir/r) or remdesivir) use, drug-drug interactions (DDIs) and adverse drug reactions (ADRs) in elderly patients (75 and over), hospitalized with mild-to-moderate COVID-19 between July 2022 and June 2023. (3) Results: Out of 491 patients (mean age: 86.9 years), 180 (36.7%) received nirmatrelvir/r, 78 (15.9%) received remdesivir, and 233 (47.4%) received no antiviral therapy. No association was found between the choice of antiviral and the demographic or medical data. No serious ADR was observed. Nirmatrelvir/r dosage adjustment was inadequate in 65% of patients with renal impairment. In total, 128 patients (71%) on nirmatrelvir/r had potential pharmacokinetic DDIs, with 43 resulting in a possibly related ADR. In the remdesivir group, pharmacodynamic DDIs were more frequent, with QTc prolongation risk in 56 patients (72%). Only 20 patients underwent follow-up ECG, revealing QTc prolongation in 4. (4) Conclusions: There is an underutilization of antivirals despite their justified indications. Nirmatrelvir/r dosage was rarely adjusted to renal function. Dose adjustments and closer monitoring are needed due to the high risk of drug interactions.
Asunto(s)
Adenosina Monofosfato , Alanina , Antivirales , Tratamiento Farmacológico de COVID-19 , Interacciones Farmacológicas , Ritonavir , SARS-CoV-2 , Humanos , Antivirales/uso terapéutico , Antivirales/efectos adversos , Femenino , Masculino , Anciano de 80 o más Años , Estudios Retrospectivos , Alanina/análogos & derivados , Alanina/uso terapéutico , Alanina/efectos adversos , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Adenosina Monofosfato/efectos adversos , SARS-CoV-2/efectos de los fármacos , Anciano , Ritonavir/uso terapéutico , Ritonavir/efectos adversos , COVID-19/virología , Adenosina/análogos & derivadosRESUMEN
BACKGROUND: Literature on the safety of remdesivir in hospitalized COVID-19 patients with severe renal impairment is limited. We aimed to investigate the safety and effectiveness of remdesivir in this population. METHODS: We conducted a retrospective cohort study of adult hospitalized COVID-19 patients who received remdesivir between April 2022 and October 2022. Outcomes were compared between estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 and ≥30 mL/min/1.73 m2 groups. The primary safety outcomes were acute kidney injury (AKI) and bradycardia, while the primary effectiveness outcomes included mortality in COVID-19-dedicated wards and hospital mortality. Secondary outcomes included laboratory changes, disease progression, and recovery time. RESULTS: A total of 1,343 patients were recruited, with 307 (22.9%) in the eGFR <30 group and 1,036 (77.1%) in the eGFR ≥30 group. Patients with an eGFR <30 had higher risks of AKI (adjusted hazard ratio [aHR] 2.92, 95% CI 1.93-4.44) and hospital mortality (aHR 1.47, 95% CI 1.06-2.05) but had comparable risks of bradycardia (aHR 1.15, 95% CI 0.85-1.56) and mortality in dedicated wards (aHR 1.43, 95% CI 0.90-2.28) than patients with an eGFR ≥30. Risk of disease progression was higher in the eGFR <30 group (adjusted odds ratio 1.62, 95% CI 1.16-2.26). No difference between the two groups in laboratory changes and recovery time. CONCLUSIONS: Hospitalized COVID-19 patients receiving remdesivir with severe renal impairment had an increased risk of AKI, hospital mortality, and COVID-19 disease progression compared to patients without severe renal impairment.
Asunto(s)
Lesión Renal Aguda , Adenosina Monofosfato , Alanina , Antivirales , Tratamiento Farmacológico de COVID-19 , Tasa de Filtración Glomerular , Mortalidad Hospitalaria , Hospitalización , SARS-CoV-2 , Humanos , Alanina/análogos & derivados , Alanina/uso terapéutico , Alanina/efectos adversos , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Adenosina Monofosfato/efectos adversos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Antivirales/uso terapéutico , Antivirales/efectos adversos , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/epidemiología , Hospitalización/estadística & datos numéricos , COVID-19/complicaciones , COVID-19/mortalidad , Resultado del Tratamiento , Insuficiencia Renal/epidemiología , Bradicardia/inducido químicamente , Bradicardia/epidemiología , AdultoRESUMEN
Twenty-eight individuals who experienced proximal renal tubulopathy (PRT, Fanconi syndrome) while receiving tenofovir disoproxil initiated tenofovir alafenamide (TAF) and were followed for 5 years. None developed recurrent PRT or experienced significant changes in estimated glomerular filtration rate (by creatinine or cystatin-C), albuminuria, proteinuria, retinol-binding proteinuria, fractional excretion of phosphate, alkaline phosphatase, or bone mineral density at the lumbar spine. These data suggest that TAF is a well tolerated treatment option for individuals vulnerable to developing PRT.
Asunto(s)
Adenina , Alanina , Fármacos Anti-VIH , Síndrome de Fanconi , Infecciones por VIH , Tenofovir , Humanos , Tenofovir/efectos adversos , Tenofovir/uso terapéutico , Tenofovir/análogos & derivados , Alanina/efectos adversos , Alanina/uso terapéutico , Masculino , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/complicaciones , Adenina/análogos & derivados , Adenina/efectos adversos , Adenina/uso terapéutico , Femenino , Síndrome de Fanconi/inducido químicamente , Adulto , Persona de Mediana EdadRESUMEN
BACKGROUND: The use of remdesivir in patients with coronavirus disease 2019 (COVID-19) and severe renal impairment has been approved; however, limited clinical data exist. Accordingly, we aimed to compare outcomes and adverse events associated with remdesivir in hospitalized patients with COVID-19, with and without severe renal impairment. METHODS: Hospitalized patients with COVID-19 undergoing a 5-day remdesivir course at Taipei Veterans General Hospital from April 1 to July 31, 2022, were enrolled. Comparative analysis of outcomes and safety between patients with or without severe renal impairment (estimated glomerular filtration rate of < 30 mL/min per 1.73 m2) were conducted. Prognostic factors associated with 28-day mortality in patients with severe renal impairment were investigated using logistic regression analysis. RESULTS: A total of 671 hospitalized patients, including 132 patients with severe renal impairment, who received a 5-day course of remdesivir were analyzed. The 28-day mortality was higher in patients with severe renal impairment than in patients without severe renal impairment (15.2% vs. 7.8%). The proportion of patients with acute kidney injury (AKI) and deteriorated liver function after completing remdesivir therapy was similar between the patients with and without severe renal impairment, and the recovery rate of AKI was similar in both groups. The sequential organ failure assessment score was an independent factor associated with 28-day mortality in patients with severe renal impairment. CONCLUSIONS: Remdesivir was well-tolerated in hospitalized patients with COVID-19, regardless of renal function. Our findings support the recent recommendation to administer remdesivir in patients with severe renal impairment.
Asunto(s)
Lesión Renal Aguda , Adenosina Monofosfato , Alanina , Antivirales , Tratamiento Farmacológico de COVID-19 , COVID-19 , Hospitalización , Insuficiencia Renal , SARS-CoV-2 , Humanos , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Adenosina Monofosfato/efectos adversos , Alanina/análogos & derivados , Alanina/uso terapéutico , Alanina/efectos adversos , Masculino , Femenino , Anciano , Antivirales/uso terapéutico , Antivirales/efectos adversos , Persona de Mediana Edad , Resultado del Tratamiento , Hospitalización/estadística & datos numéricos , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/mortalidad , COVID-19/mortalidad , COVID-19/complicaciones , Anciano de 80 o más Años , Estudios Retrospectivos , Taiwán/epidemiología , Tasa de Filtración GlomerularAsunto(s)
Adenosina Monofosfato , Alanina , Hipersensibilidad a las Drogas , Síndrome de Kounis , Humanos , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/efectos adversos , Alanina/análogos & derivados , Alanina/efectos adversos , Síndrome de Kounis/etiología , Síndrome de Kounis/diagnóstico , Hipersensibilidad a las Drogas/etiología , Hipersensibilidad a las Drogas/diagnóstico , Antivirales/efectos adversos , Tratamiento Farmacológico de COVID-19Asunto(s)
Adenosina Monofosfato , Alanina , Hipersensibilidad a las Drogas , Síndrome de Kounis , Humanos , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/efectos adversos , Alanina/análogos & derivados , Alanina/efectos adversos , Hipersensibilidad a las Drogas/etiología , Hipersensibilidad a las Drogas/diagnóstico , Síndrome de Kounis/etiología , Síndrome de Kounis/diagnóstico , Antivirales/efectos adversos , Tratamiento Farmacológico de COVID-19RESUMEN
Antiretroviral therapy (ART) has significantly enhanced the outlook for people with HIV(PWH), yet certain ART medications can adversely affect the renal function of these patients. Of particular concern is the nephrotoxicity associated with tenofovir disoproxil fumarate (TDF). Compared to TDF, tenofovir alafenamide (TAF), another prodrug of tenofovir (TFV), results in lower TFV plasma levels, thereby alleviating the TFV-associated mitochondrial toxicity on proximal renal tubular cells. Currently, numerous clinical trials and real-world studies have demonstrated the favorable renal safety profile of ART regimens incorporating TAF for PWH. This paper seeks to consolidate the available evidence regarding the renal safety of TAF-based regimens in PWH, encompassing both the general PWH and those with renal impairment or predisposing factors, in order to offer recommendations and insights for TAF clinical application.
Asunto(s)
Adenina , Alanina , Fármacos Anti-VIH , Infecciones por VIH , Tenofovir , Humanos , Tenofovir/efectos adversos , Tenofovir/uso terapéutico , Tenofovir/análogos & derivados , Infecciones por VIH/tratamiento farmacológico , Alanina/efectos adversos , Alanina/uso terapéutico , Alanina/análogos & derivados , Adenina/análogos & derivados , Adenina/efectos adversos , Adenina/uso terapéutico , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Riñón/efectos de los fármacosRESUMEN
BACKGROUND: Integrase strand-transfer inhibitors (INSTIs) and tenofovir alafenamide have been associated with weight gain in several clinical trials and observational cohorts. However, whether weight gain associated with INSTIs and tenofovir alafenamide confers a higher risk of weight-related clinical events is unclear. We aimed to assess whether changes in BMI differentially increase hypertension or dyslipidaemia risk in people with HIV receiving INSTIs, tenofovir alafenamide, or both versus other contemporary regimens. METHODS: This multicentre, prospective observational study analysed prospective data from RESPOND, an international consortium of HIV cohorts for which recruitment began in 2017 and is still ongoing from HIV clinics and hospitals in 37 European countries and Australia. Participants were eligible if they were aged 18 years or older, receiving INSTI-containing antiretroviral therapy (ART) regimens or a contemporary non-INSTI, did not have hypertension or dyslipidaemia at baseline, and had baseline and at least two follow-up BMI, lipid, and blood pressure measurements. We excluded participants without baseline CD4 or HIV RNA results and those receiving non-ART medications associated with weight changes, including antipsychotics and mood stabilisers, corticosteroids, insulin, and insulin secretagogues. They were followed up from baseline until the earliest hypertension or dyslipidaemia event, their last visit, or Dec 31, 2021, whichever was earlier. The primary outcomes were incidence of hypertension and dyslipidaemia, for which we used multivariable Poisson regression adjusted for time-updated BMI to determine unadjusted and adjusted incidence rate ratios (IRRs) of hypertension and dyslipidaemia in people receiving INSTIs, tenofovir alafenamide, or both, and tested for interaction between time-updated ART regimen and BMI. FINDINGS: Of the 35 941 RESPOND participants, 9704 (7327 [75·5 %] male and 2377 [24·5%] female) were included in the hypertension analysis and 5231 (3796 [72·6%] male and 1435 [27·4%] female) were included in the dyslipidaemia analysis. In the univariable model, hypertension was more common in individuals receiving an INSTI with tenofovir alafenamide (IRR 1·70, 95% CI 1·54-1·88) or an INSTI without tenofovir alafenamide (1·41, 1·30-1·53) compared with those receiving neither INSTIs nor tenofovir alafenamide. Adjustment for time-updated BMI and confounders attenuated risk in participants receiving an INSTI with (IRR 1·48, 1·31-1·68) or without (1·25, 1·13-1·39) tenofovir alafenamide. Similarly, dyslipidaemia was more common in participants using tenofovir alafenamide with an INSTI (IRR 1·24, 1·10-1·40) and tenofovir alafenamide alone (1·22, 1·03-1·44) than in participants using neither INSTI nor tenofovir alafenamide. Adjustment for BMI and confounders attenuated the risk in participants receiving tenofovir alafenamide with an INSTI (adjusted IRR 1·21, 1·07-1·37), whereas the risk in those receiving tenofovir alafenamide alone became non-significant (1·15, 0·96-1·38). The associations between increasing BMI and risk of hypertension and dyslipidaemia did not differ between participants receiving different ART regimens (pinteraction=0·46 for hypertension; pinteraction=0·31 for dyslipidaemia). INTERPRETATION: Although residual confounding cannot be entirely excluded, the use of INSTIs was associated with incident hypertension, and the use of tenofovir alafenamide was associated with dyslipidaemia, with the latter association partly mediated by weight gain. These results reiterate the need for hypertension and dyslipidaemia screening in people with HIV. FUNDING: The CHU St Pierre Brussels HIV Cohort, The Austrian HIV Cohort Study, The Australian HIV Observational Database, The AIDS Therapy Evaluation in the Netherlands national observational HIV cohort, The Brighton HIV Cohort, The National Croatian HIV Cohort, The EuroSIDA cohort, The Frankfurt HIV Cohort Study, The Georgian National AIDS Health Information System, The Nice HIV Cohort, The ICONA Foundation, The Modena HIV Cohort, The PISCIS Cohort Study, The Swiss HIV Cohort Study, The Swedish InfCare HIV Cohort, The Royal Free HIV Cohort Study, The San Raffaele Scientific Institute, The University Hospital Bonn HIV Cohort, The University of Cologne HIV Cohort, Merck Life Sciences, ViiV Healthcare, and Gilead Sciences.
Asunto(s)
Índice de Masa Corporal , Dislipidemias , Infecciones por VIH , Hipertensión , Tenofovir , Tenofovir/análogos & derivados , Humanos , Femenino , Masculino , Infecciones por VIH/tratamiento farmacológico , Tenofovir/efectos adversos , Tenofovir/uso terapéutico , Hipertensión/epidemiología , Hipertensión/inducido químicamente , Estudios Prospectivos , Dislipidemias/inducido químicamente , Dislipidemias/epidemiología , Persona de Mediana Edad , Adulto , Inhibidores de Integrasa VIH/efectos adversos , Inhibidores de Integrasa VIH/uso terapéutico , Alanina/efectos adversos , Australia/epidemiología , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Aumento de Peso/efectos de los fármacos , Europa (Continente)/epidemiología , Factores de Riesgo , Quimioterapia Combinada/efectos adversosRESUMEN
BACKGROUND: Coformulated bictegravir, emtricitabine, and tenofovir alafenamide is a single-tablet regimen and was efficacious and well tolerated in children and adolescents with HIV (aged 6 years to <18 years) in a 48-week phase 2/3 trial. In this study, we report data from children aged at least 2 years and weighing 14 kg to less than 25 kg. METHODS: We conducted this open-label, multicentre, multicohort, single-arm study in South Africa, Thailand, Uganda, and the USA. Participants were virologically suppressed children with HIV, aged at least 2 years, weighing 14 kg to less than 25 kg. Participants received bictegravir (30 mg), emtricitabine (120 mg), and tenofovir alafenamide (15 mg) once daily, switching to bictegravir (50 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg) upon attaining a bodyweight of at least 25 kg. The study included pharmacokinetic evaluation at week 2 to confirm the dose of coformulated bictegravir, emtricitabine, and tenofovir alafenamide for this weight band by comparing with previous adult data. Primary outcomes were bictegravir area under the curve over the dosing interval (AUCtau) and concentration at the end of the dosing interval (Ctau) at week 2, and incidence of treatment-emergent adverse events and laboratory abnormalities until the end of week 24 in all participants who received at least one dose of bictegravir, emtricitabine, and tenofovir alafenamide. This study is registered with ClinicalTrials.gov, NCT02881320. FINDINGS: Overall, 22 participants were screened (from Nov 14, 2018, to Jan 11, 2020), completed treatment with bictegravir, emtricitabine, and tenofovir alafenamide (until week 48), and entered an extension phase. The geometric least squares mean (GLSM) ratio for AUCtau for bictegravir was 7·6% higher than adults (GLSM ratio 107·6%, 90% CI 96·7-119·7); Ctau was 34·6% lower than adults (65·4%, 49·1-87·2). Both parameters were within the target exposure range previously found in adults, children, or both". Grade 3-4 laboratory abnormalities occurred in four (18%) participants by the end week 24 and six (27%) by the end of week 48. Drug-related adverse events occurred in three participants (14%) by the end of week 24 and week 48; none were severe. No Grade 3-4 adverse events, serious adverse events, or adverse events leading to discontinuation occurred by the end of week 24 and week 48. INTERPRETATION: Data support the use of single-tablet coformulated bictegravir (30 mg), emtricitabine (120 mg), and tenofovir alafenamide (15 mg) for treatment of HIV in children aged at least 2 years and weighing 14 kg to less than 25 kg. FUNDING: Gilead Sciences.
Asunto(s)
Adenina , Alanina , Amidas , Fármacos Anti-VIH , Emtricitabina , Infecciones por VIH , Compuestos Heterocíclicos con 3 Anillos , Compuestos Heterocíclicos de 4 o más Anillos , Piperazinas , Piridonas , Tenofovir , Tenofovir/análogos & derivados , Humanos , Emtricitabina/farmacocinética , Emtricitabina/administración & dosificación , Emtricitabina/uso terapéutico , Emtricitabina/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Tenofovir/farmacocinética , Tenofovir/administración & dosificación , Tenofovir/efectos adversos , Tenofovir/uso terapéutico , Niño , Masculino , Femenino , Fármacos Anti-VIH/farmacocinética , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/uso terapéutico , Preescolar , Alanina/farmacocinética , Alanina/efectos adversos , Compuestos Heterocíclicos de 4 o más Anillos/farmacocinética , Compuestos Heterocíclicos de 4 o más Anillos/efectos adversos , Compuestos Heterocíclicos de 4 o más Anillos/administración & dosificación , Amidas/farmacocinética , Adolescente , Piridonas/farmacocinética , Piridonas/efectos adversos , Compuestos Heterocíclicos con 3 Anillos/farmacocinética , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Compuestos Heterocíclicos con 3 Anillos/administración & dosificación , Piperazinas/efectos adversos , Piperazinas/farmacocinética , Adenina/análogos & derivados , Adenina/farmacocinética , Adenina/efectos adversos , Adenina/administración & dosificación , Adenina/uso terapéutico , Tailandia , Estados Unidos , Sudáfrica , Combinación de Medicamentos , Uganda , Carga Viral/efectos de los fármacosRESUMEN
BACKGROUND: We aimed to evaluate the cardiac adverse events (AEs) in hospitalized patients with coronavirus disease 2019 (COVID-19) who received remdesivir plus standard of care (SoC) compared with SoC alone (control), as an association was noted in some cohort studies and disproportionality analyses of safety databases. METHODS: This post hoc safety analysis is based on data from the multicenter, randomized, open-label, controlled DisCoVeRy trial in hospitalized patients with COVID-19. Any first AE that occurred between randomization and day 29 in the modified intention-to-treat (mITT) population randomized to either remdesivir or control group was considered. Analysis was performed using Kaplan-Meier survival curves, and Kaplan-Meier estimates were calculated for event rates. RESULTS: Cardiac AEs were reported in 46 (11.2%) of 410 and 48 (11.3%) of 423 patients in the mITT population (n = 833) enrolled in the remdesivir and control groups, respectively. The difference between both groups was not significant (hazard ratio [HR], 1.0; 95% confidence interval [CI], .7-1.5; P = .98), even when serious and nonserious cardiac AEs were evaluated separately. The majority of reports in both groups were of arrhythmic nature (remdesivir, 84.8%; control, 83.3%) and were associated with a favorable outcome. There was no significant difference between the two groups in the occurrence of cardiac AE subclasses, including arrhythmic events (HR, 1.1; 95% CI, .7-1.7; P = .68). CONCLUSIONS: Remdesivir treatment was not associated with an increased risk of cardiac AEs compared with control in patients hospitalized with moderate or severe COVID-19. These results are consistent with other randomized, controlled trials and meta-analyses. Clinical Trials Registration. NCT04315948; EudraCT 2020-000936-23.
Asunto(s)
Adenosina Monofosfato , Alanina , Antivirales , Tratamiento Farmacológico de COVID-19 , COVID-19 , Hospitalización , SARS-CoV-2 , Humanos , Alanina/análogos & derivados , Alanina/uso terapéutico , Alanina/efectos adversos , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Adenosina Monofosfato/efectos adversos , Masculino , Femenino , Antivirales/uso terapéutico , Antivirales/efectos adversos , Persona de Mediana Edad , Anciano , Hospitalización/estadística & datos numéricos , Cardiopatías/inducido químicamente , AdultoRESUMEN
Remdesivir (RDV) is the mainstay antiviral therapy for moderate to severe COVID-19. Although remdesivir was the first drug approved for COVID-19, information about its efficacy and safety profile is limited in a significant segment of the population, such as people with underlying diseases, the elderly, children, and pregnant and lactating women. The efficacy and safety profile of RDV in disease progression, renal impairment, liver impairment, immunosuppression, geriatrics, pediatrics, pregnancy, and breastfeeding in COVID-19 patients was evaluated. The databases searched included Embase, Scopus, and PubMed. Only English language studies enrolling specific subpopulations with COVID-19 and treated with RDV were included. Thirty-nine clinical trials, cohorts, cross-sectional studies, and case series/reports were included. Most supported the benefits of RDV therapy for COVID-19 patients, such as lessening the duration of hospitalization, alleviating respiratory complications, and reducing mortality. Adverse effects of RDV, including liver and kidney impairment, were, for the most part, moderate to mild, supporting the safety profile of RDV therapy. RDV therapy was well tolerated, no new safety signals were detected, and liver function test abnormalities were the most common adverse events. Moreover, RDV, for the most part, was effective in managing the complications of COVID-19 and reducing mortality in these patients, except for patients with kidney impairment. Future studies, including RCTs, should include these subpopulations of patients to avoid delays associated with receiving proper medication through compassionate use programs.
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Adenosina Monofosfato , Alanina , Antivirales , Tratamiento Farmacológico de COVID-19 , COVID-19 , Humanos , Alanina/análogos & derivados , Alanina/uso terapéutico , Alanina/efectos adversos , Antivirales/uso terapéutico , Antivirales/efectos adversos , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Adenosina Monofosfato/efectos adversos , Embarazo , Femenino , Niño , Anciano , SARS-CoV-2/efectos de los fármacosRESUMEN
Immunocompromised patients with hematologic malignancies, particularly those treated with anti-CD20 antibodies such as rituximab and obinutuzumab, are known to be at risk of prolonged infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Prolonged administration or combination therapy with antiviral medications reportedly yields favorable outcomes in these patients. However, knowledge regarding the adverse events associated with such therapeutic approaches is limited. Herein, we report a case of acute acalculous cholecystitis (AAC) following extended administration of nirmatrelvir/ritonavir (NMV/r) in a 68-year-old Japanese man with persistent SARS-CoV-2 infection. The patient had received obinutuzumab and bendamustine for follicular lymphoma and was diagnosed with coronavirus disease 2019 (COVID-19) approximately one year after treatment initiation with these drugs. Subsequently, he was admitted to a different hospital, where he received antiviral drugs, monoclonal antibodies, and steroids. Despite these interventions, the patient relapsed and was subsequently transferred to our hospital due to persistent SARS-CoV-2 infection. Remdesivir administration was ineffective, leading to the initiation of extended NMV/r therapy. One week later, he exhibited elevated gamma-glutamyl transpeptidase (GGT) levels, and one month later, he developed AAC. Cholecystitis was successfully resolved via percutaneous transhepatic gallbladder drainage and administration of antibiotics. We speculate that extended NMV/r administration, in addition to COVID-19, may have contributed to the elevated GGT and AAC. During treatment of persistent SARS-CoV-2 infection with extended NMV/r therapy, patients should be carefully monitored for the appearance of findings suggestive of biliary stasis and the development of AAC.
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Colecistitis Alitiásica , Antivirales , Tratamiento Farmacológico de COVID-19 , COVID-19 , Ritonavir , SARS-CoV-2 , Humanos , Masculino , Anciano , Colecistitis Alitiásica/tratamiento farmacológico , Colecistitis Alitiásica/inducido químicamente , Colecistitis Alitiásica/virología , Ritonavir/uso terapéutico , Ritonavir/administración & dosificación , Ritonavir/efectos adversos , COVID-19/complicaciones , Antivirales/uso terapéutico , Antivirales/administración & dosificación , Alanina/análogos & derivados , Alanina/administración & dosificación , Alanina/uso terapéutico , Alanina/efectos adversos , Linfoma Folicular/tratamiento farmacológico , Huésped Inmunocomprometido , Anticuerpos Monoclonales HumanizadosRESUMEN
Tenofovir alafenamide (TAF), a prodrug of tenofovir, delivers high levels of active drug to hepatocytes and is given in a lower dose than tenofovir disoproxil fumarate (TDF). TAF reduces viral replication in patients with chronic hepatitis B (CHB) similar to TDF and has shown a lower risk of the renal and bone toxicities associated with TDF use. This post-marketing surveillance study examined the safety and effectiveness of TAF in treatment-naïve and -experienced CHB patients who received TAF for 144 weeks at real-world clinical sites in Japan. Safety assessments included the incidence of adverse drug reactions (ADRs), renal and bone events, and changes in selected laboratory parameters. Effectiveness was based on the proportion of patients with HBV DNA levels below the lower limit of quantitation or <29 IU/mL. This analysis included 580 patients; 18.4% of whom were treatment-naïve. The cumulative incidence of ADRs was 0.21 per 100 person-months, and the incidence of serious ADRs was 0.01 (95% CI, 0.00-0.04) per 100 person-months. There were no ADRs of declines in estimated glomerular filtration rates, renal failure or proximal tubulopathy. The most common ADR was hypophosphataemia in seven (1.2%) patients. Two (0.4%) patients each had decreased blood phosphorus, bone mineral density decreased, dizziness and alopecia. Overall, the proportion of virologically suppressed patients increased from 68.8% at baseline to 97.5% at Week 144. These results confirm the real-world safety and effectiveness of TAF in Japanese patients with CHB and are consistent with the findings of other evaluations of the safety and efficacy of TAF in CHB.
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Hepatitis B Crónica , Humanos , Hepatitis B Crónica/tratamiento farmacológico , Japón , Alanina/efectos adversos , Tenofovir/efectos adversos , Adenina/efectos adversos , Antivirales/efectos adversosRESUMEN
INTRODUCTION: Safinamide is a recent antiparkinsonian drug that modulates both dopaminergic and glutamatergic systems with positive effects on motor and nonmotor symptoms of Parkinson's disease (PD). Here, we aimed to describe the efficacy and safety of safinamide in the Italian PD patients in real-life conditions. METHODS: We performed a sub-analysis of the Italian cohort of the SYNAPSES study, a multi-country, multi-center, retrospective-prospective cohort observational study, designed to investigate the use of safinamide in routine clinical practice. Patients received for the first time a treatment with safinamide and were followed up for 12 months. The analysis was conducted on the overall population and in subgroups of interest: i) patients > 75 years, ii) patients with relevant comorbidities and iii) patients affected by psychiatric symptoms. RESULTS: Italy enrolled 616/1610 patients in 52 centers, accounting for 38% of the entire SYNAPSES cohort. Of the patients enrolled, 86.0% were evaluable at 12 months, with 23.3% being > 75 years, 42.4% with psychiatric conditions and 67.7% with relevant comorbidities. Safinamide was effective on motor symptoms and fluctuations as measured through the Unified PD rating scale III and IV scores, and on the total score, without safety issues in none of the subgroups considered. CONCLUSION: The SYNAPSES data related to Italian patients confirms the good safety profile of safinamide even in special groups of patients. Motor fluctuations and motor impairment improved at the follow-up suggesting the significant role of safinamide in managing motor symptoms in PD patients.
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Bencilaminas , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/tratamiento farmacológico , Estudios Retrospectivos , Estudios Prospectivos , Antiparkinsonianos/uso terapéutico , Alanina/efectos adversos , Levodopa/uso terapéuticoRESUMEN
BACKGROUND: Lipid-lowering effect was observed during treatment with tenofovir disoproxil fumarate (TDF) for chronic hepatitis B (CHB). However, the metabolic features in patients switching from TDF to tenofovir alafenamide (TAF) remain unclear. AIMS: To compare the impacts of switching from TDF to TAF or from entecavir to TAF on body weight and metabolic features in patients with CHB. METHODS: This was a multi-centre, prospective, observational study in patients with CHB on TDF or entecavir who switched to TAF. Baseline characteristics, lipid profile and sugar profile were determined. This study received IRB approval from each hospital. RESULTS: We enrolled 177 patients on TDF (99) or entecavir (78) and followed them for 48 weeks after the switch to TAF. At baseline, TDF-experienced patients had lower serum triglyceride, total cholesterol, high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol than entecavir-experienced patients. The switch from TDF to TAF significantly increased body weight, triglyceride, total cholesterol, HDL, LDL, fasting glucose, glycaemic haemoglobin, insulin and insulin resistance. The switch from entecavir to TAF did not affect these measures. There was no significant difference in atherosclerotic cardiovascular disease risk scores between groups. CONCLUSIONS: The switch from TDF to TAF was associated with weight gain, derangements of lipid profile, and increased insulin resistance in patients with CHB. Long-term effects on these metabolic features need further investigation.
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Infecciones por VIH , Hepatitis B Crónica , Resistencia a la Insulina , Humanos , Tenofovir/efectos adversos , Hepatitis B Crónica/tratamiento farmacológico , Estudios Prospectivos , Alanina/efectos adversos , Adenina , Colesterol , Aumento de Peso , Peso Corporal , TriglicéridosRESUMEN
BACKGROUND: Data on patients switched to tenofovir alafenamide (TAF) from nucleos(t)ide analogues (NUCs) other than tenofovir disoproxil fumarate are limited. AIMS: To assess the treatment and renal/bone safety outcomes following the switch to TAF. METHODS: We prospectively enrolled adult patients with chronic hepatitis B (CHB) who switched from any NUC to TAF at 14 centres in Japan, Korea, Taiwan and the U.S. Study outcomes were viral suppression (VR; HBV DNA < 20 IU/mL), biochemical response (BR; alanine aminotransferase normalisation), and changes in estimated glomerular filtration rate (eGFR) and T-scores (L-spine) by bone absorptiometry by 24 months after switch to TAF. RESULTS: We enrolled 270 eligible patients. Mean age was 58.1; 58.2% were male; 12.2% had cirrhosis and 73.3% previously received entecavir monotherapy. VR rate increased significantly from 95.2% to 98.8% by 24 months after the switch to TAF (p = 0.014). Between the switch and 24 months later, the mean spine T-score improved significantly from -1.43 ± 1.36 to -1.17 ± 1.38 (p < 0.0001), while there was no significant change in mean eGFR (88.4 ± 16.9-89.5 ± 16.3 mL/min/1.73 m2 , p = 0.13). On multivariable analysis adjusted for age, sex, baseline spine T-score and prior TDF or adefovir dipivoxil use, male sex was significantly associated with lower risk of worsening spine T-score (odds ratio: 0.29, p = 0.020), while age was significantly associated with a higher risk of worsening chronic kidney disease stage (OR: 1.07, p = 0.019). CONCLUSIONS: At 24 months after the switch to TAF, VR rates and spine bone density improved significantly while renal function remained stable.