Tenofovir vs lamivudine plus adefovir in chronic hepatitis B: TENOSIMP-B study.

AIM: To demonstrate the non-inferiority (15% non-inferiority limit) of monotherapy with tenofovir disoproxil fumarate (TDF) vs the combination of lamivudine (LAM) plus adefovir dipivoxil (ADV) in the maintenance of virologic response in patients with chronic hepatitis B (CHB) and prior failure with LAM. METHODS: This study was a Phase IV prospective, randomized, open, controlled study with 2 parallel groups (TDF and LAM+ADV) of adult patients with hepatitis B e antigen (HBeAg)-negative CHB, prior failure with LAM, on treatment with LAM+ADV for at least 6 mo, without prior resistance to ADV and with an undetectable viral load at the start of the study, in 14 Spanish hospitals. The follow-up time for each patient was 48 wk after randomization, with quarterly visits in which the viral load, biochemical and serological parameters, adverse effects, adherence to treatment and consumption of hospital resources were analysed. RESULTS: Forty-six patients were evaluated [median age: 55.4 years (30.2-75.2); 84.8% male], including 22 patients with TDF and 24 with LAM+ADV. During study development, hepatitis B virus DNA (HBV-DNA) remained undetectable, all patients remained HBeAg negative, and hepatitis B surface antigen (HBsAg) positive. Alanine aminotransferase (ALT) values at the end of the study were similar in the 2 groups (25.1 ± 7.65, TDF vs 24.22 ± 8.38, LAM+ADV, P = 0.646). No significant changes were observed in creatinine or serum phosphorus values in either group. No significant differences between the 2 groups were noted in the identification of adverse effects (AEs) (53.8%, TDF vs 37.5%, LAM+ADV, P = 0.170), and none of the AEs which occurred were serious. Treatment adherence was 95.5% and 83.3% in the TDF and the LAM+ADV groups, respectively (P = 0.488). The costs associated with hospital resource consumption were significantly lower with the TDF treatment than the LAM+ADV treatment (€4943 ± 1059 vs €5811 ± 1538, respectively, P < 0.001). CONCLUSION: TDF monotherapy proved to be safe and not inferior to the LAM+ADV combination therapy in maintaining virologic response in patients with CHB and previous LAM failure. In addition, the use of TDF generated a significant savings in hospital costs.

Cost-effectiveness analysis of tenofovir disoproxil fumarate for treatment of chronic hepatitis B in China.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) is newly available for treatment of chronic hepatitis B patients in China. To date, no study has been conducted to examine the cost-effectiveness of this treatment. The aim of this study was to estimate the cost-effectiveness of TDF versus four oral nucleos(t)ide analogs [lamivudine (LAM), adefovir (ADV), telbivudine (LdT), and entecavir (ETV)] and from a pharmacoeconomic perspective to assess current drug pricing for TDF. METHODS: Based on Chinese healthcare perspectives, a Markov model was applied to simulate the lifetime (40-year time span) costs and quality-adjusted life-years (QALYs) for five different monotherapy strategies. Two kinds of rescue combination strategies (base-case: LAM + ADV then ETV + ADV; alternative: directly using ETV + ADV) were separately considered for treatment of patients refractory to monotherapy. Model parameters (including disease transition, cost, and utility) were obtained from previous Chinese population studies. Both branded and generic drugs were separately analyzed. Study model uncertainties were assessed by one-way and probabilistic sensitivity analyses. Two-way sensitivity analysis was used to explore uncertainties between efficacy and price of TDF. RESULTS: In the base-case analysis, the lowest lifetime cost and the best cost-effectiveness ratio were obtained by ETV, which was considered the reference treatment. LAM, ADV, and LdT treatments had significantly greater costs and lower efficacies. Compared to ETV, TDF was more effective but also more expensive. The incremental cost-effectiveness ratios of TDF versus ETV were much higher than the willing-to-pay threshold of $20,466 US dollars (USD) per QALY gained (3 × gross domestic product per capita of China, 2014). TDF would be the most cost-effective strategy if the annual cost did not exceed $2260 USD and $1600 USD for branded and generic drugs, respectively. CONCLUSIONS: For Chinese chronic hepatitis B patients, ETV is still the most cost-effective strategy over TDF and other nucleos(t)ide analogs, with a threshold of $20,466 USD/QALY gained.

[CLINICAL AND PHARMACOECONOMIC RESULTS OF THE USAGE OF VARIOUS HIV REVERSE TRANSCRIPTASE INHIBITORS IN THE SCHEMES OF ANTIRETROVIRAL THERAPY OF PATIENT RECEIVING THERAPY FOR THE CHRONIC HEPATITIS C VIRUS].

Efficacy, safety, and economical aspects of treatment with abacavir, zidovudine, stavudine, and phosphazide in the schemes of antiretroviral therapy of the HIV-infected patients receiving therapy for hepatitis C virus were tested. Clinical, immunological, and virologic efficacy of treatment and dynamics of hemoglobin, thrombocytes, and alanine aminotransferase as markers of common adverse events recorded at the start of the antiviral therapy of chronic hepatitis C and after 4, 8, 12, 24, 48 weeks of the treatment were evaluated. The usage of these drugs in the schemes of antiretroviral therapy exhibited efficacy, high tolerability and safety for all HIV reverse transcriptase inhibitors.

Cost-effectiveness comparison of lamivudine plus adefovir combination treatment and nucleos(t)ide analog monotherapies in Chinese chronic hepatitis B patients.

BACKGROUND/AIM: Lamivudine (LAM) plus adefovir (ADV) combination therapy is clinically efficacious for treating chronic hepatitis B (CHB) patients in China, but no pharmacoeconomic evaluations of this strategy are available. The aim of this study was to examine the cost-effectiveness of LAM plus ADV combination treatment compared with five other nucleos(t)ide analog monotherapies (LAM, ADV, telbivudine [TBV], entecavir [ETV], and tenofovir [TDF]). METHODS: To simulate the lifetime (40-year time span) costs and quality-adjusted life-years (QALYs) for different therapy options, a Markov model that included five initial monotherapies and LAM plus ADV combination as an initial treatment was developed. Two kinds of rescue combination strategies (base-case: LAM + ADV then ETV + ADV; alternative: direct use of ETV + ADV) were considered separately for treating patients refractory to initial therapy. One-way and probabilistic sensitivity analyses were used to explore model uncertainties. RESULTS: In base-case analysis, ETV had the lowest lifetime cost and served as the reference therapy. Compared to the reference, LAM, ADV, and TBV had higher costs and lower efficacy, and were completely dominated by ETV. LAM plus ADV combination therapy or TDF was more efficacious than ETV, but also more expensive. Although the incremental cost-effectiveness ratios of combination therapy or TDF were both higher than the willingness-to-pay threshold of $20,466/QALY gained for the reference treatment, in an alternative scenario analysis LAM plus ADV combination therapy would be the preferable treatment option. CONCLUSION: ETV and LAM plus ADV combination therapy are both cost-effective strategies for treating Chinese CHB patients.

Cost-effectiveness of Lamivudine, Telbivudine, Adefovir Dipivoxil and Entecavir on decompensated hepatitis B virus-related cirrhosis.

OBJECTIVE: To evaluate the cost-effectiveness of lamivudine (LMV), telbivudine (LdT), adefovir dipivoxil (ADV) and entecavir (ETV) on decompensated hepatitis B virus-related cirrhosis. PATIENTS AND METHODS: 1332 patients with decompensated hepatitis B virus-related cirrhosis were randomly assigned into 5 groups with different clinical treatment including LMV treatment, LdT treatment, ADV treatment, LMV+ADV treatment and ETV treatment. And then the liver function, Child-Pugh scores, sero-conversion of HBeAg/HBeAb, polymerase gene mutations, cost-effectiveness, incremental cost-effectiveness and side effects were investigated and further analyzed. RESULTS: LMV, ADV, LdT, LMV+ADV and ETV were all effective on decreasing Child-Pugh scores and conversing negatively hepatitis B virus (HBV) DNA and HBeAg, whereas LMV+ADV and ETV more effective than LMV, ADV and LdT. HBV DNA polymerase genotypic mutations were rare in the 5 groups. The less mutation rate was found in the LMV+ADV and ETV group than in the LMV, ADV and LdT group. Compared to the cost-effectiveness and incremental cost-effectiveness ratio, ETV was the optimal selection, LMV+ADV was the alternative selection and LMV was the cheapest option. The side effects of the 5 plans were all rare and could be controlled. CONCLUSIONS: LMV, ADV, LdT, LMV+ADV and ETV were all effective on treatment of decompensated hepatitis B virus-related cirrhosis whereas ETV and LMV+ADV were recommended.

Cost-effectiveness analysis of lamivudine, telbivudine, and entecavir in treatment of chronic hepatitis B with adefovir dipivoxil resistance.

The purpose of this study was to analyze the cost-effectiveness of lamivudine (LMV), telbivudine (LdT), and entecavir (ETV) in treatment of chronic hepatitis B with adefovir dipivoxil (ADV) resistance. Two hundred and fifty-two patients were recruited and screened for resistance to ADV and randomly assigned into three groups: LMV + ADV, LdT + ADV, and ETV + ADV. The ratio of biochemical response, virological response, seroconversion of hepatitis Be antigen (HBeAg)/hepatitis Be antibody (HBeAb), viral breakthrough, and the cost and effectiveness of treatments were analyzed. A comparison of the results of the ratio of biochemical response, virological response and seroconversion of HBeAg/HBeAb, showed no statistical difference between the three groups, with the economic cost of LMV + ADV the lowest, LdT + ADV the middle, and ETV + ADV the highest. The side effects of the three plans are all rare and tolerable. LMV + ADV is the optimal rescue strategy, and LdT + ADV the alternative selection in the economically less developed regions, while ETV + ADV was used in the economically developed regions.

HIV-serodiscordant couples desiring a child: 'treatment as prevention,' preexposure prophylaxis, or medically assisted procreation?

OBJECTIVE: We sought to assess the residual risk of HIV transmission, cost, and cost-effectiveness of various strategies that can help fertile HIV-uninfected female/HIV-1-infected male on combination antiretroviral therapy with plasma HIV RNA <50 copies/mL couples to have a child: (1) unprotected sexual intercourse (treatment as prevention); (2) treatment as prevention limited to fertile days (targeting fertile days); (3) treatment as prevention with preexposure prophylaxis (tenofovir/emtricitabine); (4) treatment as prevention and preexposure prophylaxis limited to fertile days; or (5) medically assisted procreation (MAP). STUDY DESIGN: This was a model-based, cost-effectiveness analysis performed from a French societal perspective. Input parameters derived from international literature included: 85% probability of live births in different strategies, 0.0083%/mo HIV transmission risk with unprotected vaginal intercourse, 1% HIV mother-to-child transmission rate, and 4.4% birth defect risk related to combination antiretroviral therapy when the mother is infected at conception. Targeting fertile days and preexposure prophylaxis were estimated to decrease the risk of HIV transmission by 80% and 67%, respectively, and by 93.4% for preexposure prophylaxis limited to fertile days (the relative risk of transmission considering the combination of both strategies assuming to be (1-80%)*(1-67%) = 16.6% in basecase). Tenofovir/emtricitabine monthly cost was set at €540. RESULTS: The HIV transmission risk was highest with treatment as prevention and lowest for MAP (5.4 and 0.0 HIV-infected women/10,000 pregnancies, respectively). Targeting fertile days was more effective than preexposure prophylaxis (0.9 vs 1.8) and associated with lowest costs. Preexposure prophylaxis limited to fertile days was more effective than targeting fertile days (0.3 vs 0.9) with a cost-effectiveness ratio of €1,130,000/life year saved; MAP cost-effectiveness ratio when compared with preexposure prophylaxis limited to fertile days was €3,600,000/life year saved. Results were robust to multiple sensitivity analyses. CONCLUSION: Targeting fertile days is associated with a low risk of HIV transmission in fertile HIV-uninfected female/male with controlled HIV-1 infection couples. The risk is lower with preexposure prophylaxis limited to fertile days, or MAP, but these strategies are associated with unfavorable cost-effectiveness ratios under their current costs.

Limited hepatitis B immunoglobulin with potent nucleos(t)ide analogue is a cost-effective prophylaxis against hepatitis B virus after liver transplantation.

BACKGROUND: Prophylaxis against hepatitis B virus (HBV) recurrence after orthotopic liver transplantation (OLT) includes lifelong hepatitis B immunoglobulin (HBIG) and oral antiviral agent(s). In the presence of high-genetic-barrier nucleos(t)ide analogues, the need for lifelong HBIG is questioned. We evaluated the safety and cost-effectiveness of a limited HBIG course. METHODS: OLT from 2006 to 2013 were reviewed. Patients with pre-OLT hepatitis B virus surface antigen who received HBV prophylaxis with 2 HBIG doses (anhepatic and first post-operative day; 10,000 units/dose) and potent nucleos(t)ide analogues were included. The primary end point was HBV recurrence (HBV-DNA detection). RESULTS: Thirteen patients (primary transplants) were included, median Model for End-Stage Liver Disease score was 18, and there was no fulminant failure; HBV-DNA was detected in 4 patients at OLT. After OLT, 10 patients received entecavir and/or tenofovir. Median follow-up was 23 months. One recurrence occurred (7.7%) at month 13 (HBV-DNA: 14 IU/mL); the graft maintained excellent function. This minimal viremic expression is related to hepatocellular carcinoma recurrence with neoplastic replication carrying integrated HBV-DNA; thus, there is no defined HBV viral recurrence. No graft loss or patient death was related to HBV recurrence. The 1-year patient and graft survival rate was 84.6%. Cost-savings in the first year was $178,100 per patient when compared with Food and Drug Administration-approved HBIG dosing. CONCLUSIONS: In the era of potent oral nucleos(t)ide analogues, a limited HBIG course appears to be cost-effective in preventing HBV recurrence.

Pre-exposure prophylaxis accessibility research and evaluation (PrEPARE Study).

Tenofovir-emtricitabine (TDF-FTC) has demonstrated effectiveness as HIV preexposure prophylaxis (PrEP), but it is not commonly prescribed. Our study was designed to determine the barriers preventing utilization of PrEP among men who have sex with men (MSM), the group at greatest risk for HIV infection in the United States. A population-based sample of MSM presenting for HIV testing at 'Early Test' HIV testing and counseling sites in San Diego, California were offered PrEP and education about potential efficacy. Eligible individuals reported having unprotected sex within the past 12 months and who tested negative for HIV were offered study participation. Despite offering procedures for evaluation and prescription for PrEP to 416 eligible subjects, less than 0.5 % of participants received the drug. Surveys collected from 54 of those who declined study participation revealed multiple barriers to PrEP among MSM including cost, low perceived risk of infection and concerns about taking a daily medication and potential long-term side effects. Efforts should be made to address these barriers, especially lowering the cost of TDF-FTC, education about PrEP side effects and awareness of HIV risks.

ACOG Committee Opinion no 595: Committee on Gynecologic Practice: Preexposure prophylaxis for the prevention of human immunodeficiency virus.

Preexposure prophylaxis is defined as the administration of antiretroviral medications to individuals who are not infected with human immunodeficiency virus (HIV) and are at the highest risk of acquiring HIV infection. In combination with other proven HIV-prevention methods, preexposure prophylaxis may be a useful tool for women at the highest risk of HIV acquisition. Obstetrician-gynecologists involved in the care of women using preexposure prophylaxis must reinforce adherence to daily medication. The Centers for Disease Control and Prevention's guidance for preexposure prophylaxis is likely to evolve in the coming years, and obstetrician-gynecologists should remain aware of new developments in this area. Risk reduction for all women at risk of HIV infection should include counseling about testing, safe-sex practices (including condom use), and other behavioral interventions.

A cost-utility analysis of drug treatments in patients with HBeAg-positive chronic hepatitis B in Thailand.

BACKGROUND: Only lamivudine has been included for patients with chronic hepatitis B (CHB) in the National List of Essential Drugs (NLED), a pharmaceutical reimbursement list in Thailand. There have also been no economic evaluation studies of CHB drug treatments conducted in Thailand yet. In order to fill this gap in policy research, the objective of this study was to compare the cost-utility of each drug therapy (Figure 1) with palliative care in patients with HBeAg-positive CHB. METHODS: A cost-utility analysis using an economic evaluation model was performed to compare each drug treatment for HBeAg-positive CHB patients. A Markov model was used to estimate the relevant costs and health outcomes during a lifetime horizon based on a societal perspective. Direct medical costs, direct non-medical costs, and indirect costs were included, and health outcomes were denoted in life years (LYs) and quality-adjusted life years (QALYs). The results were presented as an incremental cost effectiveness ratio (ICER) in Thai baht (THB) per LY or QALY gained. One-way sensitivity and probabilistic sensitivity analyses were applied to investigate the effects of model parameter uncertainties. RESULTS: The ICER values of providing generic lamivudine with the addition of tenofovir when drug resistance occurred, generic lamivudine with the addition of tenofovir based on the road map guideline, and tenofovir monotherapy were -14,000 (USD -467), -8,000 (USD -267) , and -5,000 (USD -167) THB per QALY gained, respectively. However, when taking into account all parameter uncertainties in the model, providing generic lamivudine with the addition of tenofovir when drug resistance occurred (78% and 75%) and tenofovir monotherapy (18% and 24%) would yield higher probabilities of being cost-effective at the societal willingness to pay thresholds of 100,000 (USD 3,333) and 300,000 (USD 10,000) THB per QALY gained in Thailand, respectively. CONCLUSIONS: Based on the policy recommendations from this study, the Thai government decided to include tenofovir into the NLED in addition to generic lamivudine which is already on the list. Moreover, the results have shown that the preferred treatment regimen involves using generic lamivudine as the first-line drug with tenofovir added if drug resistance occurs in HBeAg-positive CHB patients.

Systemic preexposure prophylaxis for HIV: translating clinical data to clinical practice.

OBJECTIVE: To assess the real-world implications of oral tenofovir-emtricitabine (TDF-FTC) for HIV preexposure prophylaxis (PrEP) in clinical practice and highlight important considerations for its implementation. DATA SOURCES: A search of PubMed (January 1996 through June 2013) was conducted using the terms HIV preexposure prophylaxis, HIV prevention, tenofovir, and emtricitabine. Abstracts from 2012-2013 HIV/AIDS conferences were also reviewed. STUDY SELECTION AND DATA EXTRACTION: All pertinent original studies and review articles published in English were evaluated for inclusion. Reference citations from identified articles were examined for additional content. DATA SYNTHESIS: Although antiretroviral therapy has been highly successful in reducing AIDS outcomes and death in HIV-infected patients worldwide, transmission of HIV remains a major global health problem. The recent approval of oral TDF-FTC for HIV PrEP represents the latest biomedical intervention to help control this epidemic. Four published randomized studies evaluated the efficacy and safety of this combination to prevent HIV transmission in several at-risk populations, including men who have sex with men, serodiscordant couples, and heterosexuals residing in endemic regions. Overall, these studies demonstrated significant risk reductions in the incidence of new HIV infections with good short-term tolerability. Despite promising results from clinical studies, several limitations may hinder the utility of PrEP in clinical practice. Most importantly, PrEP was studied in the context of a comprehensive prevention program, including intensive counseling on adherence, high-risk behaviors, and traditional preventative measures. If PrEP is implemented without these adjunct measures, concerns about failure and increased resistance may eventually be realized. CONCLUSION: The greatest impact of PrEP, both clinically and financially, will likely arise from judicious application in select high-risk populations. If used appropriately, PrEP has the potential to augment reductions in the current incidence of new HIV infections, and pharmacists will have an important role in the careful selection and counseling of these targeted populations.

Cost-effectiveness of tenofovir gel in urban South Africa: model projections of HIV impact and threshold product prices.

BACKGROUND: There is urgent need for effective HIV prevention methods that women can initiate. The CAPRISA 004 trial showed that a tenofovir-based vaginal microbicide had significant impact on HIV incidence among women. This study uses the trial findings to estimate the population-level impact of the gel on HIV and HSV-2 transmission, and price thresholds at which widespread product introduction would be as cost-effective as male circumcision in urban South Africa. METHODS: The estimated 'per sex-act' HIV and HSV-2 efficacies were imputed from CAPRISA 004. A dynamic HIV/STI transmission model, parameterised and fitted to Gauteng (HIV prevalence of 16.9% in 2008), South Africa, was used to estimate the impact of gel use over 15 years. Uptake was assumed to increase linearly to 30% over 10 years, with gel use in 72% of sex-acts. Full economic programme and averted HIV treatment costs were modelled. Cost per DALY averted is estimated and a microbicide price that equalises its cost-effectiveness to that of male circumcision is estimated. RESULTS: Using plausible assumptions about product introduction, we predict that tenofovir gel use could lead to a 12.5% and 4.9% reduction in HIV and HSV-2 incidence respectively, by year 15. Microbicide introduction is predicted to be highly cost-effective (under $300 per DALY averted), though the dose price would need to be just $0.12 to be equally cost-effective as male circumcision. A single dose or highly effective (83% HIV efficacy per sex-act) regimen would allow for more realistic threshold prices ($0.25 and $0.33 per dose, respectively). CONCLUSIONS: These findings show that an effective coitally-dependent microbicide could reduce HIV incidence by 12.5% in this setting, if current condom use is maintained. For microbicides to be in the range of the most cost-effective HIV prevention interventions, product costs will need to decrease substantially.

Lamivudine compared with newer antivirals for prophylaxis of hepatitis B core antibody positive livers: a cost-effectiveness analysis.

There is concern over the development of de novo hepatitis B in patients receiving liver transplants from hepatitis B surface antigen negative, hepatitis B core antibody positive donors. Current practice is to place such patients on indefinite lamivudine prophylaxis; however, there is a small risk of breakthrough infection and newer antivirals for hepatitis B are available. The objective of this study was to determine the cost-effectiveness of lamivudine compared with the newer agents, tenofovir and entecavir, in the prophylaxis setting using a Markov model. Three strategies were examined which consisted of either lamivudine or entecavir monoprophylaxis with tenofovir add-on therapy after breakthrough or tenofovir monoprophylaxis with emtricitabine add-on therapy after breakthrough. In the base case scenario, lamivudine was the most cost-effective option at a threshold of $100 000 per quality-adjusted life-year and this remained robust despite parameter uncertainty. Tenofovir had an incremental cost-effectiveness ratio of $3 540 194.77 while other strategies were superior to entecavir therapy. Until drug costs decrease, lamivudine remains the most cost-effective option for hepatitis B prophylaxis in the liver transplant setting.

Single-tablet regimens in HIV: does it really make a difference?

OBJECTIVES: Review of the available data on the currently available single-tablet regimens (STRs), from the analysis of efficacy and safety to the key points of value in terms of adherence, quality of life and pharmacoeconomic evaluation. METHODS: For this narrative review, literature searches have been performed in PubMed, IndexRevMed and Cochrane, using the search terms HIV, single-tablet, one-pill, single dose, fixed-dose, and STR. These have been reviewed and complemented with the most recent publications of interest. RESULTS: Fixed-dose combinations are a significant advance in antiretroviral treatment simplification, contributing to an increase in compliance with complex chronic therapies, thus improving patients' quality of life. Reducing the number of pills and daily doses is associated with higher adherence and better quality of life. As a fixed-dose combination tablet given once daily, EFV/FTC/TDF was the first available STR combining efficacy, tolerability and convenience, with the simplest dosing schedule and smallest numbers of pills of any ART combination therapy. The RPV/FTC/TDF is a next-generation NNRTI-based STR, a once daily complete ART regimen for the treatment of HIV-1 infection. Recently the combination of EVG/COBI/FTC/TDF was also approved by the European Commission, and is the first integrase inhibitor-based STR. Receiving antiretroviral therapy as once daily STR is associated with both clinical and economic benefits, which confirms previous research. CONCLUSIONS: The associated benefits of STRs provide a valid strategy for the treatment of HIV-infected patients.

Incorporated antivirals for chronic hepatitis B in Brazil: a cost-effectiveness analysis.

OBJECTIVE: To evaluate the cost-effectiveness of different drug therapies for chronic hepatitis B in adult patients. METHODS: Using a Markov model, a hypothetical cohort of 40 years for HBeAg-positive or HBeAg-negative patients was constructed. Adefovir, entecavir, tenofovir and lamivudine (with rescue therapy in cases of viral resistance) were compared for treating adult patients with chronic hepatitis B undergoing treatment for the first time, with high levels of alanine aminotransferase, no evidence of cirrhosis and without HIV co-infection. Values for cost and effect were obtained from the literature, and expressed in effect on life years (LY). A discount rate of 5% was applied. Univariate sensitivity analysis was conducted to assess model uncertainties. RESULTS: Initial treatment with entecavir or tenofovir showed better clinical outcomes. The lowest cost-effectiveness ratio was for entecavir in HBeAg-positive patients (R$ 4,010.84/LY) and lamivudine for HBeAg-negative patients (R$ 6,205.08/LY). For HBeAg-negative patients, the incremental cost-effectiveness ratio of entecavir (R$ 14,101.05/LY) is below the threshold recommended by the World Health Organization. Sensitivity analysis showed that variation in the cost of drugs may make tenofovir a cost-effective alternative for both HBeAg-positive and HBeAg-negative patients. CONCLUSIONS: Entecavir is the recommended alternative to start treating patients with chronic hepatitis B in Brazil. However, if there is a reduction in the cost of tenofovir, it can become a cost-effective alternative.

Economic evaluation of treatments for chronic hepatitis B

The aim of this study was to conduct a cost-utility study of adefovir, entecavir, interferon alpha, pegylated interferon alpha, lamivudine and tenofovir for chronic hepatitis B in the context of Brazilian Public Health Care System. A systematic review was carried out for efficacy and safety. Another review was performed to collect utility data and transition probabilities between health states. A Markov model was developed in a time horizon of 40 years with annual cycles for three groups of: HBeAg positive, HBeAg negative, and all patients. These strategies were compared to a fourth group that received no treatment. Discount rates of 5% were applied and sensitivity analyses were performed. Tenofovir offered the best cost-utility ratio for the three evaluated models: U$397, U$385 and U$384 (per QALY, respectively, for HBeAg positive, negative, and all patients). All other strategies were completely dominated because they showed higher costs and lower effectiveness than tenofovir. The sequence of cost-utility in the three models was: tenofovir, entecavir, lamivudine, adefovir, telbivudine, pegylated interferon alpha, and interferon alpha. In the sensitivity analysis, adefovir showed lower cost-utility than telbivudine in some situations. The study has some limitations, primarily related to the creation of scenarios and modeling. In this study, tenofovir presented the best cost-utility ratio. The results obtained in this study will be valuable in decision-making and in the review of the clinical protocol, mainly involving the allocation of available resources for health care.

Antivirais incorporados no Brasil para hepatite B cronica: analise de custo-efetividade / Antivirales incorporados en Brasil para hepatitis B cronica: analisis de costo-efectividad / Incorporated antivirals for chronic hepatitis B in Brazil: a cost-effectiveness analysis

OBJETIVO Avaliar o custo-efetividade de diferentes tratamentos medicamentosos para hepatite B crônica entre pacientes adultos. MÉTODOS Utilizando modelo de Markov, construiu-se coorte hipotética de 40 anos para pacientes HBeAg-positivo ou HBeAg-negativo. Foram comparados os usos de adefovir, entecavir, tenofovir e lamivudina (com terapia de resgate em caso de resistência viral) para tratamento de pacientes adultos com hepatite B crônica, virgens de tratamento, com elevados níveis de alanina aminotransferase, sem evidência de cirrose e sem coinfecção por HIV. Valores para custo e efeito foram obtidos da literatura. A medida do efeito foi expressa em anos de vida ganhos (AVG). Taxa de desconto de 5% foi aplicada. Análise de sensibilidade univariada foi conduzida para avaliar incertezas do modelo. RESULTADOS O tratamento inicial com entecavir ou tenofovir apresentou melhores resultados clínicos. As menores razões custo-efetividade foram de entecavir para pacientes HBeAg-positivo (R$ 4.010,84/AVG) e lamivudina para pacientes HBeAg-negativo (R$ 6.205,08/AVG). Para pacientes HBeAg-negativo, a razão custo-efetividade incremental de entecavir (R$ 14.101,05/AVG) está abaixo do limiar recomendado pela Organização Mundial da Saúde. Análise de sensibilidade mostrou que variação nos custos dos medicamentos pode tornar tenofovir alternativa custo-efetiva tanto para pacientes HBeAg-positivo quanto para HBeAg-negativo. CONCLUSÕES Entecavir é alternativa recomendada para iniciar o tratamento de pacientes com hepatite B crônica no Brasil. Contudo, se houver redução no custo de tenofovir, esta pode se tornar alternativa mais custo-efetiva. .

OBJETIVO Evaluar el costo-efectividad de diferentes tratamientos medicamentosos para hepatitis B crónica entre pacientes adultos. MÉTODOS Utilizando el modelo de Markov, se construyó cohorte hipotética de 40 años para pacientes HBeAg-positivo o HBeAg-negativo. Se compararon los usos de adefovir, entecavir, tenofovir y lamivudina (con terapia de rescate en caso de resistencia viral) para tratamiento de pacientes adultos con hepatitis B crónica, vírgenes de tratamiento, con elevados niveles de alanina aminotransferasa, sin evidencia de cirrosis y sin coinfección por VIH. Valores para costo y efecto fueron obtenidos de la literatura y efecto en años de vida ganados (AVG). Tasa de descuento de 5% fue aplicada. Análisis de sensibilidad univariado fue conducido para evaluar incertidumbres del modelo. RESULTADOS El tratamiento inicial con entecavir o tenofovir presentó mejores resultados clínicos. Los menores cocientes costo-efectividad fueron de entecavir para pacientes HBeAg-positivo (R.010,84/AVG) y lamivudina para pacientes HBeAg-negativo (R.205,08/AVG).Para pacientes HBeAg-negativo, el cociente costo-efectividad incrementado de entecavir (R.101,05/AVG) está por debajo del límite recomendado por la Organización Mundial de la Salud. El análisis de sensibilidad mostró que la variación en los costos de los medicamentos puede tornar tenofovir una alternativa costo-efectiva tanto para pacientes HBeAg-positivo como para los HBeAg-negativo. CONCLUSIONES Entecavir es una alternativa recomendada para iniciar el tratamiento de pacientes con hepatitis B crónica en Brasil. Sin embargo, al haber reducción en el costo de tenofovir, éste puede convertirse en una alternativa más costo-efectiva. .

OBJECTIVE To evaluate the cost-effectiveness of different drug therapies for chronic hepatitis B in adult patients. METHODS Using a Markov model, a hypothetical cohort of 40 years for HBeAg-positive or HBeAg-negative patients was constructed. Adefovir, entecavir, tenofovir and lamivudine (with rescue therapy in cases of viral resistance) were compared for treating adult patients with chronic hepatitis B undergoing treatment for the first time, with high levels of alanine aminotransferase, no evidence of cirrhosis and without HIV co-infection. Values for cost and effect were obtained from the literature, and expressed in effect on life years (LY). A discount rate of 5% was applied. Univariate sensitivity analysis was conducted to assess model uncertainties. RESULTS Initial treatment with entecavir or tenofovir showed better clinical outcomes. The lowest cost-effectiveness ratio was for entecavir in HBeAg-positive patients (R$ 4,010.84/LY) and lamivudine for HBeAg-negative patients (R$ 6,205.08/LY). For HBeAg-negative patients, the incremental cost-effectiveness ratio of entecavir (R$ 14,101.05/LY) is below the threshold recommended by the World Health Organization. Sensitivity analysis showed that variation in the cost of drugs may make tenofovir a cost-effective alternative for both HBeAg-positive and HBeAg-negative patients. CONCLUSIONS Entecavir is the recommended alternative to start treating patients with chronic hepatitis B in Brazil. However, if there is a reduction in the cost of tenofovir, it can become a cost-effective alternative. .

Economic evaluation of treatments for chronic hepatitis B.

The aim of this study was to conduct a cost-utility study of adefovir, entecavir, interferon alpha, pegylated interferon alpha, lamivudine and tenofovir for chronic hepatitis B in the context of Brazilian Public Health Care System. A systematic review was carried out for efficacy and safety. Another review was performed to collect utility data and transition probabilities between health states. A Markov model was developed in a time horizon of 40 years with annual cycles for three groups of: HBeAg positive, HBeAg negative, and all patients. These strategies were compared to a fourth group that received no treatment. Discount rates of 5% were applied and sensitivity analyses were performed. Tenofovir offered the best cost-utility ratio for the three evaluated models: U$397, U$385 and U$384 (per QALY, respectively, for HBeAg positive, negative, and all patients). All other strategies were completely dominated because they showed higher costs and lower effectiveness than tenofovir. The sequence of cost-utility in the three models was: tenofovir, entecavir, lamivudine, adefovir, telbivudine, pegylated interferon alpha, and interferon alpha. In the sensitivity analysis, adefovir showed lower cost-utility than telbivudine in some situations. The study has some limitations, primarily related to the creation of scenarios and modeling. In this study, tenofovir presented the best cost-utility ratio. The results obtained in this study will be valuable in decision-making and in the review of the clinical protocol, mainly involving the allocation of available resources for health care.