RESUMEN
Despite good hepatitis B virus (HBV) inhibition by nucleoside analogs (NAs), cases of hepatocellular carcinoma (HCC) still occur. This study proposed a non-invasive predictive model to assess HCC risk in patients with chronic hepatitis B (CHB) receiving NAs treatment. Data were obtained from a hospital-based retrospective cohort registered on the Platform of Medical Data Science Academy of Chongqing Medical University, from 2013 to 2019. A total of 501 patients under NAs treatment had their FIB-4 index updated semiannually by recalculation based on laboratory values. Patients were divided into three groups based on FIB-4 index values: < 1.45, 1.45-3.25, and ≥ 3.25. Subsequently, HCC incidence was reassessed every six months using Kaplan-Meier curves based on the updated FIB-4 index. The median follow-up time of CHB patients after receiving NAs treatment was 2.5 years. HCC incidences with FIB-4 index < 1.45, 1.45-3.25, and ≥ 3.25 were 1.18%, 1.32%, and 9.09%, respectively. Dynamic assessment showed that the percentage of patients with FIB-4 index < 1.45 significantly increased semiannually (P < 0.001), and of patients with FIB-4 index ≥ 3.25 significantly decreased (P < 0.001). HCC incidence was the highest among patients with FIB-4 index ≥ 3.25. The FIB-4 index effectively predicted HCC incidence, and its dynamic assessment could be used for regular surveillance to implement early intervention and reduce HCC risk.
Asunto(s)
Antivirales , Carcinoma Hepatocelular , Hepatitis B Crónica , Cirrosis Hepática , Neoplasias Hepáticas , Humanos , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Masculino , Femenino , Estudios Retrospectivos , Antivirales/uso terapéutico , Persona de Mediana Edad , Adulto , Factores de Riesgo , Nucleósidos/uso terapéutico , Incidencia , Medición de RiesgoRESUMEN
INTRODUCTION AND OBJECTIVES: Treatment of chronic hepatitis B (CHB) with nucelos(t)ide analogues (NA) can improve outcomes, but NA treatment is expensive for insurance plans. MATERIALS AND METHODS: The Centers for Medicare & Medicaid Services database was assessed from 2012 to 2021 to assess the use of NA for CHB in patients on Medicaid. Data extracted included the number of claims, units, and costs of each agent stratified by originator and generic. RESULTS: Over the study period, 1.9 billion USD was spent on NA, with spending peaking in 2016 at $289 million US, which has subsequently decreased. Lower expenditures since 2016 have been associated with increased use of generics. The use of generic tenofovir or entecavir led to savings of $669 million US over the study period. CONCLUSIONS: Increased generic use has significantly reduced expenditures for NA drugs; policy shifts towards generic drug use may help with sustainability.
Asunto(s)
Antivirales , Costos de los Medicamentos , Medicamentos Genéricos , Gastos en Salud , Hepatitis B Crónica , Medicaid , Humanos , Estados Unidos , Medicaid/economía , Antivirales/uso terapéutico , Antivirales/economía , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/economía , Medicamentos Genéricos/economía , Medicamentos Genéricos/uso terapéutico , Nucleósidos/uso terapéutico , Nucleósidos/economía , Tenofovir/uso terapéutico , Tenofovir/economía , Guanina/análogos & derivados , Guanina/uso terapéutico , Guanina/economíaRESUMEN
Antiretroviral Therapy (ART) is an effective treatment for human immunodeficiency virus (HIV) which has transformed the highly lethal disease, acquired immunodeficiency syndrome (AIDS), into a chronic and manageable condition. However, better methods need to be developed for enhancing patient access and adherence to therapy and for improving treatment in the long term to reduce adverse effects. From the perspective of drug discovery, one promising strategy is the development of anti-HIV prodrugs. This approach aims to enhance the efficacy and safety of treatment, promoting the development of more appropriate and convenient systems for patients. In this review, we discussed the use of the prodrug approach for HIV antiviral agents and emphasized nucleoside reverse transcriptase inhibitors. We comprehensively described various strategies that are used to enhance factors such as water solubility, bioavailability, pharmacokinetic parameters, permeability across biological membranes, chemical stability, drug delivery to specific sites/organs, and tolerability. These strategies might help researchers conduct better studies in this field. We also reported successful examples from the primary therapeutic classes while discussing the advantages and limitations. In this review, we highlighted the key trends in the application of the prodrug approach for treating HIV/AIDS.
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Síndrome de Inmunodeficiencia Adquirida , Fármacos Anti-VIH , Infecciones por VIH , Profármacos , Humanos , Inhibidores de la Transcriptasa Inversa/farmacología , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Fármacos Anti-VIH/uso terapéutico , Profármacos/farmacología , Nucleósidos/uso terapéutico , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Infecciones por VIH/tratamiento farmacológico , VIH , Transcriptasa Inversa del VIHRESUMEN
Chagas disease, caused by Trypanosoma cruzi (T. cruzi), is a serious public health problem. Current treatment is restricted to two drugs, benznidazole and nifurtimox, displaying serious efficacy and safety drawbacks. Nucleoside analogues represent a promising alternative as protozoans do not biosynthesize purines and rely on purine salvage from the hosts. Protozoan transporters often present different substrate specificities from mammalian transporters, justifying the exploration of nucleoside analogues as therapeutic agents. Previous reports identified nucleosides with potent trypanocidal activity; therefore, two 7-derivatized tubercidins (FH11706, FH10714) and a 3'-deoxytubercidin (FH8513) were assayed against T. cruzi. They were highly potent and selective, and the uptake of the tubercidin analogues appeared to be mediated by the nucleoside transporter TcrNT2. At 10 µM, the analogues reduced parasitemia >90% in 2D and 3D cardiac cultures. The washout assays showed that FH10714 sterilized the infected cultures. Given orally, the compounds did not induce noticeable mouse toxicity (50 mg/kg), suppressed the parasitemia of T. cruzi-infected Swiss mice (25 mg/kg, 5 days) and presented DNA amplification below the limit of detection. These findings justify further studies with longer treatment regimens, as well as evaluations in combination with nitro drugs, aiming to identify more effective and safer therapies for Chagas disease.
Asunto(s)
Enfermedad de Chagas , Tripanocidas , Trypanosoma cruzi , Ratones , Animales , Nucleósidos/farmacología , Nucleósidos/uso terapéutico , Tripanocidas/farmacología , Tripanocidas/uso terapéutico , Tripanocidas/química , Parasitemia/tratamiento farmacológico , Enfermedad de Chagas/tratamiento farmacológico , MamíferosRESUMEN
Yellow fever virus (YFV) is a human Flavivirus reemerging in parts of the world. While a vaccine is available, large outbreaks have recently occurred in Brazil and certain African countries. Development of an effective antiviral against YFV is crucial, as there is no available effective drug against YFV. We have identified several novel nucleoside analogs with potent antiviral activity against YFV with 50% effective concentration (EC50) values between 0.25 and 1 µM with selectivity indices over 100 in culture.
Asunto(s)
Antivirales/uso terapéutico , Nucleósidos/análogos & derivados , Nucleósidos/uso terapéutico , Fiebre Amarilla/tratamiento farmacológico , Virus de la Fiebre Amarilla/efectos de los fármacos , Virus de la Fiebre Amarilla/patogenicidad , África , Animales , Brasil , Línea Celular Tumoral , Chlorocebus aethiops , Humanos , Estructura Molecular , Células Vero , Fiebre Amarilla/virologíaAsunto(s)
Humanos , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , VIH/efectos de los fármacos , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Inhibidores de Integrasa/uso terapéutico , Lamivudine/uso terapéutico , Antirretrovirales/uso terapéutico , Nucleósidos/uso terapéutico , Evaluación de la Tecnología Biomédica , Evaluación en Salud , Análisis Costo-Beneficio , Combinación de MedicamentosRESUMEN
INTRODUCTION AND AIM: Accurately predicting the prognosis of individual patient is crucial in the management of ACLF. We aimed to establish a specific prognostic model for HBV-related ACLF patients treated with nucleoside analog (NA). MATERIAL AND METHODS: We prospectively collected 205 ACLF cases diagnosed according to the APASL criteria. A dynamic prognostic model based on APASL criteria was established and validated. To demonstrate that the model is also applicable to those within EASL criteria, we divided the patients into two groups: met APASL criteria only (group A, n = 123); met both APASL and EASL criteria (group B, n = 82). Its prognostic accuracy was also compared with chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score in group B. RESULTS: The model is: R = 0.94 x Bilirubin + 0.53 x evolution of Bilirubin - 0.45 x PT-A - 0.22 x evolution in PT-A -0.1 x PLT + 10 x anti-HBe. The area under receiver operating characteristic curve (AUC) of the model for predicting 90-day mortality was 0.86, which was significantly higher than that of model for end stage liver disease(MELD), MELD-Na, CLIF-SOFA, ΔMELD (7d) and ΔMELD-Na (7d), ΔCLIF- SOFA(7d) (all p < 0.01). The AUC of our model in the validation group was 0.79 which was superior to MELD (0.45) CLIF-SOFA (0.53) score in group B patients (p < 0.01). CONCLUSION: In conclusion, the model was superior to the conventional methods in predicting the outcomes of patients with HBV related ACLF treated with NA. It is the first description of a novel prognostic model using consecutive data in patients with HBV-induced acute-on-chronic liver failure (ACLF) treated by nucleoside analogs.
Asunto(s)
Insuficiencia Hepática Crónica Agudizada/tratamiento farmacológico , Antivirales/uso terapéutico , Técnicas de Apoyo para la Decisión , Virus de la Hepatitis B/efectos de los fármacos , Hepatitis B Crónica/tratamiento farmacológico , Modelos Biológicos , Nucleósidos/uso terapéutico , Insuficiencia Hepática Crónica Agudizada/diagnóstico , Insuficiencia Hepática Crónica Agudizada/mortalidad , Insuficiencia Hepática Crónica Agudizada/virología , Adulto , Antivirales/efectos adversos , Bilirrubina/sangre , Biomarcadores/sangre , China , Progresión de la Enfermedad , Femenino , Anticuerpos contra la Hepatitis B/sangre , Antígenos e de la Hepatitis B/inmunología , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/patogenicidad , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/mortalidad , Hepatitis B Crónica/virología , Humanos , Masculino , Persona de Mediana Edad , Nucleósidos/efectos adversos , Puntuaciones en la Disfunción de Órganos , Valor Predictivo de las Pruebas , Estudios Prospectivos , Protrombina/metabolismo , Reproducibilidad de los Resultados , Factores de Tiempo , Resultado del TratamientoRESUMEN
We aimed to investigate the influence of regulatory T cells including CD4+CD25+, CD8+CD28- and hepatitis B virus (HBV) genotype on sustained virological response and tolerance of nucleoside drugs. One hundred and thirty-seven patients were enrolled. Lamivudine was administered to 84 patients. Entecavir was administered to the other 53 patients. Before treatment, biochemical tests, HBV DNA load, HBV serum level, HBV genotype, PB CD3+, CD4+, CD8+, CD4+CD25+/CD3+, and CD8+CD28-/CD3+ frequencies were measured. Based on HBV DNA loads after 4 weeks of therapy, patients were divided into response group and suboptimal response group. The lamivudine group received treatment continuously, and then patients were categorized into non-resistance group and resistance group. Compared with the suboptimal response and resistance groups for lamivudine, CD4+CD25+/CD3+ levels were higher in the response and non-resistance groups (t=4.372, P=0.046; t=7.262, P=0.017). In the non-resistance group, CD8+CD28-/CD3+ frequency was lower than in the resistance group (t=5.527, P=0.037). Virus load and hepatitis B E antigen (HBeAg)-positive rate were significantly lower than in the response and resistance group (t=2.164, P=0.038; X2=4.239, P=0.040; t=2.015, P=0.044; X2=16.2, P=0.000). Incidence of drug resistance was high in patients with virogene type C. For the virological response to entecavir, CD8+CD28-/CD3+ level was significantly lower than that of the suboptimal response group (t=6.283, P=0.036). Response and suboptimal response groups were compared in CD3+, CD4+, CD8+, CD4+CD25+/CD3+ and virus genotype, and differences were not statistically significant (P>0.05). Baseline regulatory T cells including CD4+CD25+/CD3+ and CD8+CD28-/CD3+ frequencies have a relationship with the incidence of rapid virological response and the resistance to nucleoside drugs. Patients with HBV genotype C receiving lamivudine more often underwent drug resistance. Antiviral efficacy and the resistance to lamivudine were closely correlated with baseline factors; the same cannot be found for entecavir.
Asunto(s)
Antivirales/uso terapéutico , Guanina/análogos & derivados , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/tratamiento farmacológico , Lamivudine/uso terapéutico , Nucleósidos/uso terapéutico , Linfocitos T Reguladores , Adulto , Anciano , Resistencia a Medicamentos , Femenino , Genotipo , Guanina/uso terapéutico , Virus de la Hepatitis B/efectos de los fármacos , Hepatitis B Crónica/virología , Humanos , Masculino , Persona de Mediana Edad , Respuesta Virológica Sostenida , Linfocitos T Reguladores/inmunología , Factores de TiempoRESUMEN
We aimed to investigate the influence of regulatory T cells including CD4+CD25+, CD8+CD28- and hepatitis B virus (HBV) genotype on sustained virological response and tolerance of nucleoside drugs. One hundred and thirty-seven patients were enrolled. Lamivudine was administered to 84 patients. Entecavir was administered to the other 53 patients. Before treatment, biochemical tests, HBV DNA load, HBV serum level, HBV genotype, PB CD3+, CD4+, CD8+, CD4+CD25+/CD3+, and CD8+CD28-/CD3+ frequencies were measured. Based on HBV DNA loads after 4 weeks of therapy, patients were divided into response group and suboptimal response group. The lamivudine group received treatment continuously, and then patients were categorized into non-resistance group and resistance group. Compared with the suboptimal response and resistance groups for lamivudine, CD4+CD25+/CD3+ levels were higher in the response and non-resistance groups (t=4.372, P=0.046; t=7.262, P=0.017). In the non-resistance group, CD8+CD28-/CD3+ frequency was lower than in the resistance group (t=5.527, P=0.037). Virus load and hepatitis B E antigen (HBeAg)-positive rate were significantly lower than in the response and resistance group (t=2.164, P=0.038; X2=4.239, P=0.040; t=2.015, P=0.044; X2=16.2, P=0.000). Incidence of drug resistance was high in patients with virogene type C. For the virological response to entecavir, CD8+CD28-/CD3+ level was significantly lower than that of the suboptimal response group (t=6.283, P=0.036). Response and suboptimal response groups were compared in CD3+, CD4+, CD8+, CD4+CD25+/CD3+ and virus genotype, and differences were not statistically significant (P>0.05). Baseline regulatory T cells including CD4+CD25+/CD3+ and CD8+CD28-/CD3+ frequencies have a relationship with the incidence of rapid virological response and the resistance to nucleoside drugs. Patients with HBV genotype C receiving lamivudine more often underwent drug resistance. Antiviral efficacy and the resistance to lamivudine were closely correlated with baseline factors; the same cannot be found for entecavir.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Antivirales/uso terapéutico , Guanina/análogos & derivados , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/tratamiento farmacológico , Lamivudine/uso terapéutico , Nucleósidos/uso terapéutico , Linfocitos T Reguladores , Resistencia a Medicamentos , Genotipo , Guanina/uso terapéutico , Virus de la Hepatitis B/efectos de los fármacos , Hepatitis B Crónica/virología , Respuesta Virológica Sostenida , Linfocitos T Reguladores/inmunología , Factores de TiempoAsunto(s)
Humanos , Recién Nacido , Lactante , Preescolar , Niño , Adolescente , Polienos/uso terapéutico , Triazoles/uso terapéutico , Farmacorresistencia Fúngica , Equinocandinas/uso terapéutico , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Micosis/epidemiología , Antifúngicos/uso terapéutico , Antifúngicos/farmacología , Nucleósidos/uso terapéutico , Anfotericina B/uso terapéutico , Huésped InmunocomprometidoRESUMEN
BACKGROUND AND PURPOSE: The application of nucleos(t)ide analogues in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) has not yet been widely accepted. Therefore, we conducted a metaanalysis of prospective and retrospective studies to examine the efficacy and safety of nucleos(t)ide analogues in treating HBV-related ACLF. MATERIAL AND METHODS: Two independent reviewers identified eligible studies through electronic, and manual searches, and contact with experts. Three-month mortality was defined as the primary efficacy measure. ACLF reactivation and HBV DNA inhibition were secondary efficacy measures. Quantitative meta-analyses were performed to compare differences between nucleos(t)ide analogue and control groups. RESULTS: Five eligible studies were identified. Antiviral treatment with nucleos(t)ide analogues led to significant reduction of HBV DNA [HBV DNA reduction > 2 log: 70.4 vs. 29%, RR = 2.29, 95%CI (1.49, 3.53), P < 0.01]. ACLF patients receiving nucleos(t)ide analogue had significantly lower 3-month mortality [44.8 vs. 73.3%, RR = 0.68, 95%CI (0.54, 0.84), P < 0.01] as well as incidence of reactivation [1.80 vs. 18.4%, RR = 0.11, 95%CI (0.03, 0.43), P < 0.01] compared to those who did not. There was no significant difference in the prognosis of patients treated with entecavir or lamivudine [36.4 vs. 40.5%, RR = 0.77, 95%CI (0.45, 1.32), P = 0.35]. No drug-related adverse events were reported during follow-up. CONCLUSION: Our findings suggest that nucleos(t)ide analogue treatment reduces short-term mortality as well as reactivation of HBV-related ACLF patients. Nucleos(t)ide analogues are well-tolerated during therapy, and suggestive evidence indicates that entecavir and lamivudine confer comparable.
Asunto(s)
Antivirales/uso terapéutico , Enfermedad Hepática en Estado Terminal/tratamiento farmacológico , Hepatitis B/tratamiento farmacológico , Fallo Hepático Agudo/tratamiento farmacológico , Nucleósidos/uso terapéutico , Nucleótidos/uso terapéutico , Antivirales/efectos adversos , Biomarcadores/sangre , ADN Viral/sangre , Enfermedad Hepática en Estado Terminal/diagnóstico , Enfermedad Hepática en Estado Terminal/mortalidad , Enfermedad Hepática en Estado Terminal/virología , Hepatitis B/complicaciones , Hepatitis B/diagnóstico , Hepatitis B/mortalidad , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/crecimiento & desarrollo , Humanos , Fallo Hepático Agudo/diagnóstico , Fallo Hepático Agudo/mortalidad , Fallo Hepático Agudo/virología , Nucleósidos/efectos adversos , Nucleótidos/efectos adversos , Oportunidad Relativa , Recurrencia , Factores de Tiempo , Resultado del Tratamiento , Carga Viral , Activación ViralRESUMEN
INTRODUCTION: Balapiravir (R1626, RG1626) is the prodrug of a nucleoside analogue inhibitor of the hepatitis C virus (HCV) RNA-dependent RNA polymerase (R1479, RG1479). This phase 2, double-blind international trial evaluated the optimal treatment regimen of balapiravir plus peginterferon alfa-2a (40KD)/ribavirin. MATERIAL AND METHODS: Treatment-naive genotype 1 patients (N = 516) were randomized to one of seven treatment groups in which they received balapiravir 500, 1,000, or 1,500 mg twice daily, peginterferon alfa-2a (40KD) 180 or 90 µg/week and ribavirin 1,000/1,200 mg/day or peginterferon alfa-2a (40KD)/ribavirin. The planned treatment duration with balapiravir was reduced from 24 to 12 weeks due to safety concerns. RESULTS: The percentage of patients with undetectable HCV RNA was consistently higher in all balapiravir groups from week 2 to 12. However, high rates of dose modifications and discontinuations of one/all study drugs compromised the efficacy assessment and resulted in similar sustained virological response rates in the balapiravir groups (range 32-50%) and the peginterferon alfa-2a (40KD)/ribavirin group (43%). Balapiravir was discontinued for safety reasons in 28-36% of patients (most often for lymphopenia) and the percentage of patients with serious adverse events (especially hematological, infection, ocular events) was dose related. Serious hematological adverse events (particularly neutropenia, lymphopenia) were more common in balapiravir recipients. Two deaths in the balapiravir/peginterferon alfa-2a/ribavirin combination groups were considered possibly related to study medication. CONCLUSION: Further development of balapiravir for the treatment of chronic hepatitis C has been halted because of the unacceptable benefit to risk ratio revealed in this study (www.ClinicalTrials.gov NCT 00517439).
Asunto(s)
Genotipo , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Nucleósidos/uso terapéutico , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Adolescente , Adulto , Anciano , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Quimioterapia Combinada , Determinación de Punto Final , Femenino , Hepatitis C Crónica/sangre , Humanos , Interferón-alfa/efectos adversos , Cooperación Internacional , Masculino , Persona de Mediana Edad , Nucleósidos/efectos adversos , Polietilenglicoles/efectos adversos , ARN Viral/sangre , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Ribavirina/efectos adversos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND AND AIM: Chronic hepatitis B is a highly prevalent disease worldwide, leading to serious consequences if not properly treated. Six treatment options for chronic hepatitis B are currently provided by the Brazilian public health system. Telbivudine is a nucleoside analogue that is neither included in the Brazilian clinical protocol nor in the therapeutic guidelines for chronic hepatitis B. OBJECTIVE: The aim of this study was to evaluate the cost-effectiveness of telbivudine for the viewpoint of the Brazilian public system, comparing it to lamivudine. METHODS: A Markov model was used to project lifetime complications and costs of treatment with lamivudine or telbivudine for chronic hepatitis B in both HBeAg-positive and HBeAg-negative patients. To evaluate disease progression, probabilities and utilities of virologic response, virologic resistance, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, treatment, interruption of treatment, death and seroconversion were collected in systematic reviews. Costs were collected in DATASUS, ABC da Saúde and scientific literature. RESULTS: Higher rate of virologic response and seroconversion was obtained with telbivudine, and also higher values of quality adjusted life years. However lamivudine is associated with lower costs and also lower cost-effectiveness values. The incremental cost-effectiveness ratios for telbivudine, when compared with lamivudine, were US$ 30,575 and US$ 40,457, respectively for HBeAg-positive and HBeAg-negative patients. CONCLUSION: In chronic hepatitis B lamivudine is a more cost-effective or even cost-saving strategy when compared with telbivudine.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Lamivudine/uso terapéutico , Nucleósidos/uso terapéutico , Pirimidinonas/uso terapéutico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Antivirales/economía , Análisis Costo-Beneficio , Hepatitis B Crónica/economía , Humanos , Lamivudine/economía , Nucleósidos/economía , Pirimidinonas/economía , Inhibidores de la Transcriptasa Inversa/economía , Telbivudina , Timidina/análogos & derivadosRESUMEN
BACKGROUND AND AIM: Chronic hepatitis B is a highly prevalent disease worldwide, leading to serious consequences if not properly treated. Six treatment options for chronic hepatitis B are currently provided by the Brazilian public health system. Telbivudine is a nucleoside analogue that is neither included in the Brazilian clinical protocol nor in the therapeutic guidelines for chronic hepatitis B. OBJECTIVE: The aim of this study was to evaluate the cost-effectiveness of telbivudine for the viewpoint of the Brazilian public system, comparing it to lamivudine. METHODS: A Markov model was used to project lifetime complications and costs of treatment with lamivudine or telbivudine for chronic hepatitis B in both HBeAg-positive and HBeAg-negative patients. To evaluate disease progression, probabilities and utilities of virologic response, virologic resistance, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, treatment, interruption of treatment, death and seroconversion were collected in systematic reviews. Costs were collected in DATASUS, ABC da Saúde and scientific literature. RESULTS: Higher rate of virologic response and seroconversion was obtained with telbivudine, and also higher values of quality adjusted life years. However lamivudine is associated with lower costs and also lower cost-effectiveness values. The incremental cost-effectiveness ratios for telbivudine, when compared with lamivudine, were US$ 30,575 and US$ 40,457, respectively for HBeAg-positive and HBeAg-negative patients. CONCLUSION: In chronic hepatitis B lamivudine is a more cost-effective or even cost-saving strategy when compared with telbivudine.
Asunto(s)
Humanos , Antivirales/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Lamivudine/uso terapéutico , Nucleósidos/uso terapéutico , Pirimidinonas/uso terapéutico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Antivirales/economía , Análisis Costo-Beneficio , Hepatitis B Crónica/economía , Lamivudine/economía , Nucleósidos/economía , Pirimidinonas/economía , Inhibidores de la Transcriptasa Inversa/economíaRESUMEN
INTRODUCTION: Chronic hepatitis B is one of the most frequent infectious disease in the world and represents a serious problem of public health METHODS: A systematic review of randomized clinical trials was conducted to evaluate the efficacy of the nucleoside/nucleotide analogues (adefovir, entecavir and telbivudine) used for the treatment of chronic hepatitis B. The databases PubMed and LILACS were consulted, among others RESULTS: Twenty nine articles published between January/1970 to December/2009 were selected CONCLUSIONS: All nucleoside/nucleotide analogues demonstrate upper or similar efficacy to lamivudine. The entecavir can be appropriate for patients with chronic hepatitis B, HBeAg positive and negative treatment-naive as alternative to lamivudine, considering its low potential of viral resistance. The addition of adefovir to lamivudine presented good results in lamivudine resistant patients. The use of entecavir and telbivudine in those patients presents risk of crossed resistance. TBV is one of the most recent antivirals available, but antiviral resistance already documented represents limitation to its use as therapeutic option to LAM. Adverse events of nucleoside/nucleotide analogues were similar in characteristics, gravity and incidence when compared to the lamivudina and placebo.
Asunto(s)
Adenina/análogos & derivados , Antivirales/uso terapéutico , Guanina/análogos & derivados , Hepatitis B Crónica/tratamiento farmacológico , Nucleósidos/uso terapéutico , Organofosfonatos/uso terapéutico , Pirimidinonas/uso terapéutico , Adenina/uso terapéutico , Guanina/uso terapéutico , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Telbivudina , Timidina/análogos & derivados , Resultado del TratamientoRESUMEN
INTRODUÇÃO: A hepatite crônica B é uma das doenças infecciosas mais frequentes no mundo e constitui um grave problema de saúde pública MÉTODOS: Para avaliar a eficácia dos análogos de núcleosídeo/nucletídeo utilizados no seu tratamento (adefovir dipivoxil, entecavir e telbivudina) foi conduzida uma revisão sistemática de ensaios clínicos randomizados. Foram consultadas, dentre outras, as bases de dados PubMed e LILACS RESULTADOS: Foram selecionados 29 artigos entre os publicados de janeiro/1970 até dezembro/2009 CONCLUSÕES: Todos os análogos de núcleosídeo/nucletídeo apresentam eficácia superior ou similar à lamivudina. O entecavir pode ser indicado para o tratamento da hepatite B crônica como alternativa à lamivudina em pacientes HBeAg positivo e negativo virgens de tratamento, considerando seu baixo potencial de resistência viral. A adição de adefovir à lamivudina apresentou bons resultados em pacientes resistentes à lamivudina. O uso de entecavir e telbivudina nesses pacientes apresenta risco de resistência cruzada. Telbivudina é um dos mais recentes antivirais disponíveis, mas resistência antiviral já documentada representa limitação ao seu uso como opção terapêutica à lamivudina. Eventos adversos aos análogos de núcleosídeo/nucletídeo foram similares em características, gravidade e incidência quando comparados à lamivudina e placebo.
INTRODUCTION: Chronic hepatitis B is one of the most frequent infectious disease in the world and represents a serious problem of public health METHODS: A systematic review of randomized clinical trials was conducted to evaluate the efficacy of the nucleoside/nucleotide analogues (adefovir, entecavir and telbivudine) used for the treatment of chronic hepatitis B. The databases PubMed and LILACS were consulted, among others RESULTS: Twenty nine articles published between January/1970 to December/2009 were selected CONCLUSIONS: All nucleoside/nucleotide analogues demonstrate upper or similar efficacy to lamivudine. The entecavir can be appropriate for patients with chronic hepatitis B, HBeAg positive and negative treatment-naive as alternative to lamivudine, considering its low potential of viral resistance. The addition of adefovir to lamivudine presented good results in lamivudine resistant patients. The use of entecavir and telbivudine in those patients presents risk of crossed resistance. TBV is one of the most recent antivirals available, but antiviral resistance already documented represents limitation to its use as therapeutic option to LAM. Adverse events of nucleoside/nucleotide analogues were similar in characteristics, gravity and incidence when compared to the lamivudina and placebo.
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Humanos , Adenina/análogos & derivados , Antivirales/uso terapéutico , Guanina/análogos & derivados , Hepatitis B Crónica/tratamiento farmacológico , Nucleósidos/uso terapéutico , Ácidos Fosforosos , Pirimidinonas/uso terapéutico , Adenina/uso terapéutico , Guanina/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
Los Virus Hepatitis B (VHB) y Hepatitis C (VHC) en la actualidad son infecciones frecuentes en el hombre, afectando a una proporción significativa de la población mundial. Estos son causa frecuente de hepatitis aguda y crónica, cirrosis hepática, hepatocarcinoma y trasplante hepático. En 105 últimos años ha habido un gran progreso en el conocimiento de la epidemiología e historia natural de la infección con el VHB y VHC. Además, se han logrado grandes avances en su tratamiento y con numerosas drogas actualmente en evaluación.
Hepatitis B (HBV) and Hepatitis C (HCV) virus are common viral infections, affecting at a large worldwide population. These viruses are frequent cause of acute and chronic hepatitis, cirrhosis, hepatocellular carcinoma and liver transplantation. In the last few years, the knowledge of the epidemiology and natural history of HBV and HCV infections have markedly improved. Furthermore, considerable progress have been achieved in the efficacy of treatment and several new drugs are currently under evaluation.
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Humanos , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Antivirales/uso terapéutico , Quimioterapia Combinada , Hepatitis B Crónica/patología , Hepatitis C Crónica/patología , Nucleósidos/uso terapéutico , Nucleótidos/uso terapéuticoRESUMEN
BACKGROUND AND OBJECTIVE: This study aimed to investigate the multiple-dose pharmacokinetics of apricitabine, a novel deoxycytidine analogue reverse transcriptase inhibitor, in antiretroviral-naive patients with HIV-1 infection. METHODS: This was an international, randomized, double-blind, placebo-controlled, multicentre, dose-ranging study. Patients received 10 days' oral placebo or apricitabine 200, 400, 600 or 800 mg twice daily or 800 or 1200 mg once daily. On days 1 and 8, blood and urine samples were collected over 24 hours for pharmacokinetic analysis. Apricitabine triphosphate pharmacokinetics were investigated in peripheral blood mononuclear cells (PBMCs) on day 8. RESULTS: Overall, 63 patients (mean age 33.9 +/- 8.7 years; mean weight 71.6 +/- 15.4 kg) were randomized, and 62 patients completed the study. Apricitabine was rapidly absorbed, with peak plasma concentrations attained within approximately 1.5-2.5 hours. Pharmacokinetics were linear over the range 200-800 mg twice daily. Apricitabine was predominantly excreted via the kidneys, with no significant accumulation during repeated administration. Steady-state conditions were attained by day 8. Apricitabine triphosphate exposure in PBMCs was roughly proportional to the dose of apricitabine across the dose range 200-800 mg twice daily, with adequate correlations between plasma exposure to apricitabine (9910 ng/mL per 65 kg for 800-mg twice-daily administration) and PBMC exposure to apricitabine triphosphate (maximum concentration [C(max)] = 5.55 +/- 1.94 pmol/million cells for 800-mg twice-daily administration). Apri-citabine was well tolerated. CONCLUSION: Apricitabine shows essentially linear pharmacokinetics during repeated administration in patients with HIV-1 infection.
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Desoxicitidina/análogos & derivados , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Administración Oral , Adulto , Amilasas/biosíntesis , Amilasas/sangre , Área Bajo la Curva , Disponibilidad Biológica , Recuento de Linfocito CD4 , Cápsulas , Desoxicitidina/química , Desoxicitidina/farmacocinética , Desoxicitidina/uso terapéutico , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , VIH-1/crecimiento & desarrollo , Semivida , Cefalea/inducido químicamente , Humanos , Obstrucción Nasal/inducido químicamente , Nucleósidos/administración & dosificación , Nucleósidos/farmacocinética , Nucleósidos/uso terapéutico , Inhibidores de la Transcriptasa Inversa/efectos adversos , Inhibidores de la Transcriptasa Inversa/farmacocinética , Inhibidores de la Transcriptasa Inversa/uso terapéutico , EstereoisomerismoRESUMEN
Comparar la efectividad virológica e inmunológica, de dos esquemas, uno basado en efavirenz y el otro en lopinavir/ritonavir, ambos combinados con dos análogos nucleósidos, en pacientes con infección avanzada por VIH, sin tratamiento previo. Estudio observacional de cohorte. Falla virológica definida como carga viral >50 copias/mL en los intervalos 3 a 9, 10 a 16 y 22 a 28 meses después del inicio. Se determinó la variación de CD4+. Se realizó análisis univariado de variables asociadas falla virológica. Se aplicaron Chi², Sum Rank Testy Log Rank Test. 189 pacientes iniciaron tratamiento entre diciembre 2000 y abril 2004, 114 con efavirenz y 45 con lopinavir/ritonavir, combinados con dos análogos nucleósidos. Los grupos fueron comparables en características basales: edad en años (36,5 en efavirenz vs 36,9 en lopinavir/ritonavir, (P=0,78); CD4+ basal (183,3 en efavirenz vs. 143,7 en lopinavir/ritonavir, (P=0,14); carga viral basal (203,696 cop/mL en efavirenz vs 217,772 cop/mL en lopinavir/ritonavir, P=0,77). Para la cohorte completa 87 por ciento obtuvo valores de carga viral indetectable a los 6 meses, 58 por ciento al año y 48 por ciento a los 28 meses. El cambio en el valor de CD4+/mes (+10,5 en efavirenz vs + 9,5 en lopinavir/ritonavir, P=0,77) y el porcentaje de indetectabilidad fueron similares en ambos grupos, tomando en cuenta los pacientes que pudieron seguirse durante el período de observación, cuyo número fue disminuyendo a partir de la muestra inicial. Ambos esquemas fueron comparables en su efectividad en esta cohorte de pacientes en términos de variación de CD4+ y porcentaje de indetectabilidad de carga viral.