[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.

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.

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.

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.

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.

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.

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.

Economic savings versus health losses: the cost-effectiveness of generic antiretroviral therapy in the United States.

BACKGROUND: U.S. HIV treatment guidelines recommend branded once-daily, 1-pill efavirenz-emtricitabine-tenofovir as first-line antiretroviral therapy (ART). With the anticipated approval of generic efavirenz in the United States, a once-daily, 3-pill alternative (generic efavirenz, generic lamivudine, and tenofovir) will decrease cost but may reduce adherence and virologic suppression. OBJECTIVE: To assess the clinical effect, costs, and cost-effectiveness of a 3-pill, generic-based regimen compared with a branded, coformulated regimen and to project the potential national savings in the first year of a switch to generic-based ART. DESIGN: Mathematical simulation of HIV disease. SETTING: United States. PATIENTS: HIV-infected persons. INTERVENTION: No ART (for comparison); 3-pill, generic-based ART; and branded ART. MEASUREMENTS: Quality-adjusted life expectancy, costs, and incremental cost-effectiveness ratios (ICERs) in dollars per quality-adjusted life-year (QALY). RESULTS: Compared with no ART, generic-based ART has an ICER of $21,100/QALY. Compared with generic-based ART, branded ART increases lifetime costs by $42,500 and per-person survival gains by 0.37 QALYs for an ICER of $114,800/QALY. Estimated first-year savings, if all eligible U.S. patients start or switch to generic-based ART, are $920 million. Most plausible assumptions about generic-based ART efficacy and costs lead to branded ART ICERs greater than $100,000/QALY. LIMITATION: The efficacy and price reduction associated with generic drugs are unknown, and estimates are intended to be conservative. CONCLUSION: Compared with a slightly less effective generic-based regimen, the cost-effectiveness of first-line branded ART exceeds $100,000/QALY. Generic-based ART in the United States could yield substantial budgetary savings to HIV programs. PRIMARY FUNDING SOURCE: National Institute of Allergy and Infectious Diseases.

Should chronic hepatitis B be treated as early as possible?

OBJECTIVES: We studied the cost-effectiveness of tenofovir and entecavir in e antigen positive (CHBe+) and negative (CHBe-) chronic hepatitis B. METHODS: Using a multicenter survey including 544 patients we measured patient quality of life and attributable costs by clinical disease stage. Natural disease progression was studied in 278 patients in a single center. A Markov model was constructed to follow hypothetical cohorts of treated and untreated 40-year-old CHBe+ and CHBe- patients and 50-year-old patients with compensated cirrhosis. RESULTS: We did not find an improvement in quality of life when viral load was reduced under treatment. Transition rates to liver cirrhosis were found to be age-dependent. Assuming equal effectiveness, tenofovir dominates the entecavir strategy because of its lower price in Belgium. The incremental cost-effectiveness ratio (ICER) of tenofovir after 20 years is more favorable for treating Caucasian cirrhotic patients (mean ICER €29,000/quality-adjusted life-year [QALY]) compared with treating non-cirrhotic patients (mean ICER €110,000 and 131,000/QALY for CHB e+ and e-, respectively). Within the non-cirrhotic patients the ICER decreases with increasing cohort starting age from 30 to 50 years. CONCLUSIONS: Results of long-term models for tenofovir or entecavir treatment of CHB need to be interpreted with caution as long-term trials with hard end points are lacking. Especially the effect on HCC remains highly uncertain. Based on cost-effectiveness considerations such antiviral treatment should be targeted at patients with cirrhosis or at risk of rapid progression to this disease stage.

The cost-effectiveness of pre-exposure prophylaxis for HIV infection in South African women.

BACKGROUND: Recent trials report the short-term efficacy of tenofovir-based pre-exposure prophylaxis (PrEP) for prevention of human immunodeficiency virus (HIV) infection. PrEP's long-term impact on patient outcomes, population-level transmission, and cost-effectiveness remains unknown. METHODS: We linked data from recent trials to a computer model of HIV acquisition, screening, and care to project lifetime HIV risk, life expectancy (LE), costs, and cost-effectiveness, using 2 PrEP-related strategies among heterosexual South African women: (1) women receiving no PrEP and (2) women not receiving PrEP (a tenofovir-based vaginal microbicide). We used a South African clinical cohort and published data to estimate population demographic characteristics, age-adjusted incidence of HIV infection, and HIV natural history and treatment parameters. Baseline PrEP efficacy (percentage reduction in HIV transmission) was 39% at a monthly cost of $5 per woman. Alternative parameter values were examined in sensitivity analyses. RESULTS: Among South African women, PrEP reduced mean lifetime HIV risk from 40% to 27% and increased population discounted (undiscounted) LE from 22.51 (41.66) to 23.48 (44.48) years. Lifetime costs of care increased from $7280 to $9890 per woman, resulting in an incremental cost-effectiveness ratio of $2700/year of life saved, and may, under optimistic assumptions, achieve cost savings. Under baseline HIV infection incidence assumptions, PrEP was not cost saving, even assuming an efficacy >60% and a cost <$1. At an HIV infection incidence of 9.1%/year, PrEP achieved cost savings at efficacies ≥50%. CONCLUSIONS: PrEP in South African women is very cost-effective by South African standards, conferring excellent value under virtually all plausible data scenarios. Although optimistic assumptions would be required to achieve cost savings, these represent important benchmarks for future PrEP study design.

Substitution of tenofovir/emtricitabine for Hepatitis B immune globulin prevents recurrence of Hepatitis B after liver transplantation.

BACKGROUND: Hepatitis B immune globulin (HBIg) with or without nucleos(t)ide analogue (NA) inhibitors has been shown to prevent recurrence of hepatitis B virus (HBV) following orthotopic liver transplantation (OLT). However, the use of HBIg has many disadvantages. AIMS: The present study was performed to determine if converting patients from HBIg ± NA to combination NA therapy could prevent recurrence of HBV. METHODS: Twenty-one recipients without evidence of HBV recurrence on HBIg ± NA for ≥ 6 months were enrolled. Patients received their last injection of HBIg at the time they initiated tenofovir disoproxil fumarate/emtricitabine (TDF/FTC; Truvada(®) ) and were followed up for 31.1 ± 9.0 [range 15-47] months. RESULTS: After 1 year, 3 patients (14%) had detectable HBsAg, one of whom was non-compliant. Two of 3 with recurrence cleared HBsAg by last follow-up on TDF/FTC; the non-compliant patient became HBV DNA-undetectable with re-institution of TDF/FTC. TDF/FTC saved $12,469/year over our standard-of-care, monthly intramuscular HBIg/lamivudine. There was no evidence of a general adverse effect of TDF/FTC on renal function. However, 3 patients developed reversible acute renal failure; on renal biopsy, 1 had possible TDF/FTC-induced acute tubular necrosis. CONCLUSIONS: Substitution of TDF/FTC for HBIg prevented recurrence of HBV DNA in 100% (20/20) of patients who were compliant with the medication and led to substantial cost savings over HBIg-containing regimens.

Cost-effectiveness analysis of different rescue therapies in patients with lamivudine-resistant chronic hepatitis B in China.

BACKGROUND: Several rescue therapies have been used in patients with lamivudine (LAM)-resistant chronic hepatitis B (CHB); however, the economic outcome of these therapies is unclear. The object of the current analysis was to evaluate the lifetime cost-effectiveness of rescue therapies among patients with LAM-resistant CHB. METHODS: A Markov model was developed to simulate the clinical course of patients with LAM-resistant CHB. From the perspective of Chinese health care, a lifetime cost-utility analysis was performedfor 4 rescue strategies: adefovir (ADV), entecavir (ETV) or tenofovir (TDF) monotherapy and combination therapy using LAM and ADV. A hypothetical cohort of 45-year-old patients with genotypic or clinical LAM-resistant CHB entered the model, and the beginning health state was LAM-resistant CHB without other complications. The transition probabilities, efficacy and resistance data for each rescue therapy as well as the costs and utility data were estimated from the literature. The discount rate (3%) utilized for costs and benefits. Sensitivity analyses were used to explore the impact of uncertainty on the results. RESULTS: In LAM-resistant HBeAg-positive and HBeAg-negative CHB cohorts, TDF monotherapy and combination therapy were on the efficiency frontier for both positive and negative populations. Compared with no treatment, the use of combination therapy cost an additional $6,531.7 to gain 1 additional quality-adjusted life year (QALY) for HBeAg-positive patients and $4,571.7 to gain 1 additional QALY for HBeAg-negative patients. TDF monotherapy for HBeAg-positive patients, shows greater increase in QALYs but higher incremental cost-effectiveness ratio (ICER) in comparison with combination therapy. In probabilistic sensitivity analyses, combination therapy was the preferred option for health care systems with limited health resources, such as Chinese health care system. CONCLUSION: In Chinese patients with LAM-resistant CHB, combination therapy is a more cost-effective option than the competing rescue therapies.

Cost-effectiveness of nucleoside reverse transcriptase inhibitor pairs in efavirenz-based regimens for treatment-naïve adults with HIV infection in the United States.

OBJECTIVE: To estimate the cost-effectiveness of once-daily tenofovir/emtricitabine compared with twice-daily zidovudine/lamivudine and once-daily abacavir/lamivudine in treatment-naïve adults with HIV-1 infection in the United States. METHODS: A Markov model with four therapy lines and six health states based on CD4(+) cell-count ranges was developed to estimate lifetime costs and health outcomes. Efficacy data (virologic response and CD4(+) cell-count changes) for first-line therapy were from 144-week results of Study 934 comparing tenofovir/emtricitabine with zidovudine/lamivudine and 48-week results of Study CNA30024 comparing abacavir/lamivudine with zidovudine/lamivudine, all in combination with efavirenz. Data from Study CNA30024 for abacavir/lamivudine were adjusted to allow for an indirect comparison with tenofovir/emtricitabine. Subsequent therapy lines were based on likely baskets of antiretroviral therapy recommended by US treatment guidelines. Utility values, mortality rates, and costs (2009 US dollars) were obtained from published sources. Base-case results were tested in sensitivity and variability analyses. RESULTS: Average discounted results showed that individuals using tenofovir/emtricitabine were predicted to remain on first-line therapy for 7.7 years, accrue lifetime costs of $747,327, and experience 15.75 quality-adjusted life-years (QALYs), compared with 6.0 years, $777,090, and 15.68 QALYs for individuals using abacavir/lamivudine and 5.8 years, $778,287, and 15.44 QALYs for individuals using zidovudine/lamivudine. Tenofovir/emtricitabine was cost-effective compared with the other two first-line regimens in more than 75% of all probabilistic sensitivity analysis simulation runs for every willingness-to-pay threshold between $0 and $250,000 per QALY gained. Results were robust in variability and one-way sensitivity analyses. CONCLUSIONS: Tenofovir/emtricitabine was predicted to be more effective and cost-saving compared with abacavir/lamivudine and zidovudine/lamivudine in treatment-naïve adults with HIV-1 infection in the United States.

Cost-effectiveness of tenofovir as first-line antiretroviral therapy in India.

BACKGROUND: World Health Organization guidelines for antiretroviral treatment (ART) in resource-limited settings recommend either stavudine or tenofovir as part of initial therapy. We evaluated the clinical outcomes and cost-effectiveness of first-line ART using tenofovir in India, compared with current practice using stavudine or zidovudine. METHODS: We used a state-transition model of human immunodeficiency virus (HIV) disease to examine strategies using different nucleoside reverse-transcriptase inhibitors, combined with lamivudine and nevirapine, compared with no ART: (1) stavudine, (2) stavudine with substitution by zidovudine after 6 months, (3) zidovudine, and (4) tenofovir. Data were from the Y. R. Gaitonde Centre for AIDS Research and Education in Chennai, India, and published studies. Results. Discounted mean per person survival was 36.9 months (40.2 months undiscounted) with no ART, 115.5 months (145.3) with stavudine-containing ART, 115.7 months (145.6) with stavudine and 6-month zidovudine substitution, 115.8 months (145.6) with zidovudine-containing ART, and 125.8 months (162.0) with initial tenofovir. Discounted lifetime medical costs were $610 with no ART and ranged from $5580 with stavudine-containing ART to $5720 with zidovudine-containing ART. Initial tenofovir had an incremental cost-effectiveness ratio of $670 per year of life saved, compared with no ART, and was more economically efficient than the other regimens. RESULTS: were most sensitive to variations in the costs of first-line tenofovir, access to additional ART after treatment failure, and quality of life adjustment. CONCLUSIONS: Using tenofovir as part of first-line ART in India will improve survival, is cost-effective by international standards, and should be considered for initial therapy for HIV-infected patients in India.

Cost-utility analysis of tenofovir disoproxil fumarate in the treatment of chronic hepatitis B.

OBJECTIVE: The aim of this study was to assess the cost-effectiveness of tenofovir disoproxil fumarate (TDF) in the treatment of chronic hepatitis B (CHB) versus alternative nucleos(t)ides from a UK National Health Service (NHS) perspective. METHODS: A Markov model was used to calculate costs and benefits of nucleos(t)ide strategies in hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients with hepatitis B virus mono-infection and compensated liver disease. The model included 18 disease states representing CHB progression. Quality-of-life data and costs for severe disease states were based on published studies, while monitoring costs for other disease states were based on expert opinion. Transition probabilities for movements between states were based on a meta-analysis, clinical trials, and natural history studies. RESULTS: First-line TDF generated the highest net benefits of all 211 nucleos(t)ide strategies evaluated at a threshold of £ 20,000 per quality-adjusted life-year (QALY) gained. First-line TDF cost £ 19,084/QALY gained compared with giving lamivudine (LAM) first-line and switching to TDF when LAM resistance occurs. First-line TDF was also more effective and less costly than first-line entecavir (ETV), and showed extended dominance over first-line adefovir and strategies reserving adefovir, ETV, or combination therapy until after LAM resistance develops. For patients who have developed LAM resistance, TDF was also the most cost-effective treatment, generating greater net benefits than any other second-line strategy. CONCLUSIONS: First-line TDF is the most cost-effective treatment for patients with CHB at a £ 20,000 to £ 30,000/QALY ceiling ratio, costing £ 19,084/QALY gained compared with the next best alternative.

Cost-effectiveness of nucleoside analog therapy for hepatitis B in China: a Markov analysis.

OBJECTIVES: The aim of this study was to investigate the economic consequences of nucleoside analog therapy for hepatitis B treatment in China. METHODS: A cost-utility analysis of treatments for HBeAg-positive and HBeAg-negative chronic hepatitis B (CHB) was conducted using a Markov model, in which patients' yearly transitions between different health states were tracked. Patients were tracked as they moved between the following health states: CHB, HBeAg seroconversion (HBeAg-positive CHB patients can have this special health state), virologic resistance, virologic response, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, and death. The transition parameters were derived either from systematic reviews of the literature or from previous economic studies. Cost and utility data came from studies based on a Chinese CHB cohort. One-way sensitivity analyses as well as second-order Monte Carlo and probabilistic sensitivity analyses were performed. RESULTS: The entecavir strategy yielded the most quality-adjusted life years (QALYs) for both HBeAg-positive and HBeAg-negative patients when compared with the "no treatment," the lamivudine, the adefovir, and the telbivudine strategies. The risks of complications and mortality also decreased. In the economic analysis, the "no treatment" strategy was the least effective, whereas the entecavir strategy was both the least expensive and the most cost-effective option, followed by telbivudine and lamivudine. The probabilistic sensitivity analysis showed that the entecavir strategy would result in improved cost-effectiveness in >90% of cases at a threshold of $20,000 per QALY. In a one-way sensitivity analysis, the most influential parameters impacting the model's robustness were the utilities of the CHB and virologic response health states. CONCLUSIONS: In China, when treating both HBeAg-positive and HBeAg-negative CHB populations, entecavir is the most cost-effective option when compared with lamivudine, adefovir, and telbivudine.

HIV preexposure prophylaxis in the United States: impact on lifetime infection risk, clinical outcomes, and cost-effectiveness.

BACKGROUND: The combination of tenofovir and emtricitabine shows promise as HIV preexposure prophylaxis (PrEP). We sought to forecast clinical, epidemiologic, and economic outcomes of PrEP, taking into account uncertainties regarding efficacy, the risks of developing drug resistance and toxicity, behavioral disinhibition, and drug costs. METHODS: We adapted a computer simulation of HIV acquisition, detection, and care to model PrEP among men who have sex with men and are at high risk of HIV infection (i.e., 1.6% mean annual incidence of HIV infection) in the United States. Base-case assumptions included 50% PrEP efficacy and monthly tenofovir-emtricitabine costs of $753. We used sensitivity analyses to examine the stability of results and to identify critical input parameters. RESULTS: In a cohort with a mean age of 34 years, PrEP reduced lifetime HIV infection risk from 44% to 25% and increased mean life expectancy from 39.9 to 40.7 years (21.7 to 22.2 discounted quality-adjusted life-years). Discounted mean lifetime treatment costs increased from $81,100 to $232,700 per person, indicating an incremental cost-effectiveness ratio of $298,000 per quality-adjusted life-year gained. Markedly larger reductions in lifetime infection risk (from 44% to 6%) were observed with the assumption of greater (90%) PrEP efficacy. More-favorable incremental cost-effectiveness ratios were obtained by targeting younger populations with a higher incidence of infection and by improvements in the efficacy and cost of PrEP. CONCLUSIONS: PrEP could substantially reduce the incidence of HIV transmission in populations at high risk of HIV infection in the United States. Although it is unlikely to confer sufficient benefits to justify the current costs of tenofovir-emtricitabine, price reductions and/or increases in efficacy could make PrEP a cost-effective option in younger populations or populations at higher risk of infection. Given recent disappointments in HIV infection prevention and vaccine development, additional study of PrEP-based HIV prevention is warranted.

Modeling the cost-effectiveness of different oral antiviral therapies in patients with chronic hepatitis B.

BACKGROUND/AIMS: Chronic hepatitis B (CHB) is a common disease associated with high morbidity, mortality and impact on healthcare costs. Several oral antiviral therapies can lead to complete virologic response, which is associated with prevention of disease progression. The aim of this study was to estimate the cost-effectiveness of the oral antiviral treatments lamivudine, adefovir, telbivudine, entecavir and tenofovir, in patients with CHB. METHODS: A Markov model was used to project the lifetime complications and costs in cohorts of both HBeAg-positive and HBeAg-negative CHB patients treated with one of the above drugs or no treatment. Rescue therapy with two different combination therapies (adefovir plus lamivudine or tenofovir plus entecavir) with their corresponding costs and efficacy rates was also considered. The probabilities of disease progression were based on serum HBV DNA levels. Disease and complication costs were assessed using the perspective of the Spanish National Health System. RESULTS: The highest rate of virologic response was obtained with tenofovir, and this translated to its higher life years saved (LYS) and quality adjusted life years (QALY) compared with the rest of the alternatives in HBeAg-positive and HBeAg-negative patients. Tenofovir is associated with lower costs and higher efficacy over entecavir, telbivudine and adefovir in HBeAg-positive patients, and telbivudine and entecavir in HBeAg-negative patients. The incremental cost-effectiveness ratios with respect to the rest of the alternatives are below the common reference efficiency threshold of 30,000 euro per LYS/QALY. CONCLUSION: In chronic HBV infected patients, tenofovir is a cost-effective or even cost-saving strategy compared with other available treatment options for CHB.