Update on HIV prevention and preexposure prophylaxis.

HIV preexposure prophylaxis (PrEP) is an opportunity for clinicians to curb the 40,000 HIV infections occurring annually in the United States. PrEP is medication used by HIV-negative patients to reduce their risk of acquiring the virus. This article provides a baseline understanding of PrEP indications, prescribing, and monitoring, including a review of previously approved medication and an update on newly approved drugs, including emtricitabine/tenofovir alafenamide (F/TAF). Sexual and gender minorities are often underrepresented in the literature about PrEP, but clinicians should address risk focused on specific behaviors rather than population-level characteristics. As one of few professions with prescriptive authority, PAs have an obligation to understand and manage PrEP.

Comparative Pricing of Branded Tenofovir Alafenamide-Emtricitabine Relative to Generic Tenofovir Disoproxil Fumarate-Emtricitabine for HIV Preexposure Prophylaxis: A Cost-Effectiveness Analysis.

Background: Tenofovir alafenamide-emtricitabine (F/TAF) was recently approved as a noninferior and potentially safer option than tenofovir disoproxil fumarate-emtricitabine (F/TDF) for HIV preexposure prophylaxis (PrEP) in the United States. Objective: To estimate the greatest possible clinical benefits and economic savings attributable to the improved safety profile of F/TAF and the maximum price payers should be willing to pay for F/TAF over generic F/TDF. Design: Cost-effectiveness analysis. Data Sources: Published literature on F/TDF safety (in persons with and those without HIV) and the cost and quality-of-life effects of fractures and end-stage renal disease (ESRD). Target Population: Age-stratified U.S. men who have sex with men (MSM) using PrEP. Time Horizon: Five years. Perspective: Health care sector. Intervention: Preexposure prophylaxis with F/TAF versus F/TDF. Outcome Measures: Fractures averted, cases of ESRD averted, quality-adjusted life-years (QALYs) saved, costs, incremental cost-effectiveness ratios (ICERs), and maximum justifiable price for F/TAF compared with generic F/TDF. Results of Base-Case Analysis: Over a 5-year horizon, compared with F/TDF, F/TAF averted 2101 fractures and 25 cases of ESRD for the 123 610 MSM receiving PrEP, with an ICER of more than $7 million per QALY. At a 50% discount for generic F/TDF ($8300 per year) and a societal willingness to pay up to $100 000 per QALY, the maximum fair price for F/TAF was $8670 per year. Results of Sensitivity Analysis: Among persons older than 55 years, the ICER for F/TAF remained more than $3 million per QALY and the maximum permissible fair price for F/TAF was $8970 per year. Results were robust to alternative time horizons and PrEP-using population sizes. Limitation: Intermittent use and on-demand PrEP were not considered. Conclusion: In the presence of a generic F/TDF alternative, the improved safety of F/TAF is worth no more than an additional $370 per person per year. Primary Funding Source: National Institute of Allergy and Infectious Diseases, National Institute on Drug Abuse, National Institute of Mental Health, and Massachusetts General Hospital Executive Committee on Research.

Tenofovir prophylaxis for preventing mother-to-child hepatitis B virus transmission in China: A cost-effectiveness analysis.

OBJECTIVES: This study aimed to evaluate whether tenofovir prophylaxis for mothers with high viral loads in late pregnancy is a cost-effective way to prevent mother-to-child hepatitis B virus (HBV) transmission in China. METHODS: A decision tree Markov model was constructed for a cohort of infants born to HBV surface antigen-positive mothers in China, 2016. The expected cost and effectiveness were compared between the current active-passive immunoprophylaxis strategy and the tenofovir prophylaxis strategy, and the incremental cost-effectiveness ratio was calculated. One-way and multi-way probabilistic sensitivity analyses were performed. RESULTS: For 100,000 babies born to mothers positive for hepatitis B surface antigen, tenofovir prophylaxis strategy will prevent 2213 perinatal HBV infections and will gain 931 quality-adjusted life years when compared with the current active-passive immunoprophylaxis strategy. The incremental cost-effectiveness ratio was ï¿¥59,973 ($9087) per quality-adjusted life years gained. This result was robust over a wide range of assumptions. CONCLUSIONS: Tenofovir prophylaxis for mothers with high viral loads in late pregnancy was found to be more cost-effective than the current active-passive immunoprophylaxis alone. Embedding tenofovir prophylaxis for mothers with high virus loads into the present hepatitis B prevention strategies should be considered to further prevent mother-to-child hepatitis B transmission in China.

Cost-Effectiveness of Tenofovir Alafenamide for Treatment of Chronic Hepatitis B in Canada.

BACKGROUND/AIM: Tenofovir alafenamide (TAF) has been approved for treating chronic hepatitis B (CHB) due to a proposed better safety profile in comparison with current therapies. We evaluated the cost effectiveness of TAF and other available treatment options for hepatitis B envelope antigen (HBeAg)-positive and HBeAg-negative CHB patients from a Canadian provincial Ministry of Health perspective. METHODS: A state-transition model based on the published literature was developed to compare treatment strategies involving entecavir (ETV), tenofovir disoproxil fumarate (TDF), and TAF. It adopted a lifetime time horizon. Outcomes measured were predicted number of liver-related deaths, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS: For HBeAg-positive patients, TAF followed by ETV generated an additional 0.16 QALYs/person at an additional cost of Can$14,836.18 with an ICER of Can$94,142.71/QALY compared with TDF followed by ETV. Of the iterations, 28.7% showed that it is the optimal strategy with a Can$50,000 willingness-to-pay threshold. For HBeAg-negative patients, ETV followed by TAF would prevent an additional 13 liver-related deaths per 1000 CHB patients compared with TDF, followed by ETV. It generated an additional 0.13 QALYs/person at an additional cost of Can$59,776.53 with an ICER of Can$461,162.21/QALY compared with TDF, followed by ETV. TAF-containing strategies are unlikely to be a rational choice in either case. The results were sensitive to the HBeAg seroconversion rates and viral suppression rates of the treatments. CONCLUSIONS: Our analysis suggests that TAF is not cost effective at its current cost. A 33.4% reduction in price would be required to make it cost effective for HBeAg-positive patients with a Can$50,000 willingness-to-pay threshold.

Modelling cost-effectiveness of tenofovir for prevention of mother to child transmission of hepatitis B virus (HBV) infection in South Africa.

BACKGROUND: International sustainable development goals for the elimination of viral hepatitis as a public health problem by 2030 highlight the need to optimize strategies for prevention, diagnosis and treatment of hepatitis B virus (HBV) infection. An important priority for Africa is to have affordable, accessible and sustainable prevention of mother to child transmission (PMTCT) programmes, delivering screening and treatment for antenatal women and implementing timely administration of HBV vaccine for their babies. METHODS: We developed a decision-analytic model simulating 10,000 singleton pregnancies to assess the cost-effectiveness of three possible strategies for deployment of tenofovir in pregnancy, in combination with routine infant vaccination: S1: no screening nor antiviral therapy; S2: screening and antiviral prophylaxis for all women who test HBsAg-positive; S3: screening for HBsAg, followed by HBeAg testing and antiviral prophylaxis for women who are HBsAg-positive and HBeAg-positive. Our outcome was cost per infant HBV infection avoided and the analysis followed a healthcare perspective. RESULTS: Based on 10,000 pregnancies, S1 predicts 45 infants would be HBV-infected at six months of age, compared to 21 and 28 infants in S2 and S3, respectively. Relative to S1, S2 had an incremental cost of $3940 per infection avoided. S3 led to more infections and higher costs. CONCLUSION: Given the long-term health burden for individuals and economic burden for society associated with chronic HBV infection, screening pregnant women and providing tenofovir for all who test HBsAg+ may be a cost-effective strategy for South Africa and other low/middle income settings.

Cost-effectiveness of preexposure prophylaxis for HIV prevention for conception in the United States.

OBJECTIVE: The aim of this study was to investigate the value of coformulated Tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) for preexposure prophylaxis (PrEP) for conception in the U.S. and to identify scenarios in which 'Undetectable = Untransmittable' (U = U) may not be adequate, and rather, PrEP or assisted reproduction would improve outcomes. DESIGN: We developed a Markov cohort simulation model to estimate the incremental benefits and cost-effectiveness of PrEP compared with alternative safer conception strategies, including combination antiretroviral therapy (cART) alone for the HIV-infected partner and assisted reproductive technologies. We modelled various scenarios in which HIV RNA suppression in the male partner was less than perfect. SETTING: U.S. healthcare sector perspective. PARTICIPANTS: Serodiscordant couples in the U.S. was composed of an HIV-infected male and HIV-uninfected female seeking conception. INTERVENTION: Economic analysis. MAIN OUTCOME MEASURE(S): Cumulative risks of HIV transmission to women and babies, maternal life expectancy, discounted quality-adjusted life years (QALY), discounted lifetime medical costs and incremental cost-effectiveness ratios. RESULTS: cART with condomless intercourse limited to ovulation was the preferred HIV prevention strategy among women seeking to conceive with an HIV-infected partner who is HIV-suppressed. PrEP was not cost-effective for women who had partners who were virologically suppressed. When the probability of male partner HIV suppression was low and we assumed generic pricing of PrEP, PrEP was cost-effective, and sometimes even cost-saving compared with cART alone. CONCLUSION: From a U.S. healthcare sector perspective, when the male partner was not reliably suppressed, PrEP became economically attractive, and in some cases, cost-saving.

Considerations of antiviral treatment to interrupt mother-to-child transmission of hepatitis B virus in China.

Background: Treating high-risk women with antivirals in their third trimester is a promising intervention to further reduce perinatal transmission in neonates born to hepatitis B surface antigen positive [HBsAg(+)] mothers. Methods: We estimated the number of perinatal infections based on coverage and effectiveness of hepatitis B immunization. We compared cost-effectiveness of different approaches to identify high-risk women for antiviral treatment, by region and urban/rural residence. Results: Of the 16.59 million live births in 2015, 1.04 million infants (6.3%) were born to HBsAg(+) mothers and 268 201 infants (1.6%) to HBsAg(+) and HBeAg(+) dual-positive mothers. Despite immunoprophylaxis, 51 478 perinatal hepatitis B virus (HBV) transmissions were estimated to have occurred from HBsAg and HBeAg dual-positive mothers in 2015. Using HBeAg or HBV viral load testing to identify high-risk pregnant women and to treat them with Tenofovir, the incremental cost ranged from US$68.2 million to US$90.3 million. Assuming HBV viral load testing is available and used to guide treatment and all women with HBV viral loads >200 000 IU/ml are treated, 25 912 infections would be averted at a projected cost of US$3500 per infection averted. Conclusions: Identifying high-risk pregnant women and providing them with antiviral treatment is feasible and cost-effective to interrupt perinatal HBV transmissions. Policy options should be urgently explored in order for China to reach the HBV elimination goal of 0.1% prevalence among children by 2030.

Publicly Funded Oral Chronic Hepatitis B Treatment Patterns in Ontario over 16 Years: An Ecologic Study.

BACKGROUND: Reimbursement for the use of hepatitis B virus (HBV) treatments has not been previously reported for public payers. OBJECTIVE: To describe the number of users and total cost of HBV treatments over the last 16 years among residents of Ontario, Canada, who were covered by the public drug program. METHODS: We conducted a repeated cross-sectional study for HBV treatments reimbursed by the public drug program in Ontario from January 1, 2000, to December 31, 2015. We projected total spending to 2020 based on current utilization trends. RESULTS: HBV drug users per year increased 30-fold, from 132 users in 2000 to 4,035 users in 2015. Total spending on HBV treatments increased 150-fold, from $136,368 annually in 2000 to $21.0 million in 2015. The spending on HBV agents is projected to increase by 65%, with an estimated drug cost of $34.6 million by 2020. CONCLUSIONS: Although not reimbursed as first-line therapy, tenofovir disoproxil fumarate has become the most commonly reimbursed HBV treatment and was associated with an increase in HBV treatment use and total spending. Results of this study found that rapid growth of HBV treatments led to a sustained increase in spending for public payers in Ontario. DISCLOSURES: This study was funded by grants from the Ontario Ministry of Health and Long-Term Care (MOHLTC) and Ontario Strategy for Patient-Orientated Research (SPOR) Support Unit, which is supported by the Canadian Institutes of Health Research and the Province of Ontario. This study was also supported by the Institute for Clinical Evaluative Sciences (ICES), a non-profit research institute sponsored by the Ontario MOHLTC. The opinions, results, and conclusions reported in this article are those of the authors and are independent from the funding sources. No endorsement by ICES or the Ontario MOHLTC is intended or should be inferred. Parts of this material are based on data and information compiled and provided by the Canadian Institute for Health Information (CIHI). However, the analyses, conclusions, opinions and statements expressed herein are those of the authors and not necessarily those of CIHI. Mamdani has received honoraria from Boehringer Ingelheim, Pfizer, Bristol-Myers Squibb, and Bayer. Janssen has received research support, consulting, and/or speaking fees from Gilead, Roche, Merck, AbbVie, Bristol-Myers Squibb, Arbutus, Janssen, and MedImmune. No other authors have any conflicts of interest to declare.

In what circumstances could nondaily preexposure prophylaxis for HIV substantially reduce program costs?

OBJECTIVES: To review the main factors influencing the costs of nondaily oral preexposure prophylaxis (PrEP) with tenofovir (±emtricitabine). To estimate the cost reductions possible with nondaily PrEP compared with daily PrEP for different populations (MSM and heterosexual populations). DESIGN: Systematic review and data triangulation. METHODS: We estimated the required number of tablets/person/week for dosing regimens used in the HPTN 067/ADAPT (daily/time-driven/event-driven) and IPERGAY (on-demand) trials for different patterns of sexual intercourse. Using trial data, and behavioural and cost data obtained through systematic literature reviews, we estimated cost savings resulting from tablet reductions for nondaily versus daily oral PrEP, assuming 100% adherence. RESULTS: Among different populations being prioritized for PrEP, the median reported number of days of sexual activity varied between 0 and 2 days/week (0-1.5 days/week for MSM, 1-2 days/week for heterosexual populations). With 100% adherence and two or fewer sex-days/week, HPTN 067/ADAPT nondaily regimens reduced the number of tablets/week by more than 40% compared with daily PrEP. PrEP program costs were reduced the most in settings with high drug costs, for example, by 66-69% with event-driven PrEP for French/US populations reporting on average one sex-day/week. CONCLUSION: Nondaily oral PrEP could lower costs substantially (>50%) compared with daily PrEP, particularly in high-income countries. Adherence and efficacy data are needed to determine cost-effectiveness.

Noncommunicable diseases in adolescents with perinatally acquired HIV-1 infection in high-income and low-income settings.

PURPOSE OF REVIEW: Perinatally HIV-infected adolescents may be at increased risk of noninfectious comorbidities later in life. This review summarizes recent advances in the understanding of noncommunicable diseases (NCD) among HIV-infected adolescents in high-income and lower middle-income countries, and identifies key questions that remain unanswered. We review atherosclerotic vascular disease (AVD), chronic bone disease (CBD), chronic kidney disease (CKD), and chronic lung disease (CLD). RECENT FINDINGS: Persistent immune activation and inflammation underlie the pathogenesis of AVD, highlighting the importance of treatment adherence and maintenance of viral suppression, and the need to evaluate interventions to decrease risk. Tenofovir disoproxil fumarate (TDF) and trials of vitamin D supplementation have been the focus of recent studies of CBD with limited studies to date evaluating tenofovir alafenamide as an alternative to TDF for decreasing risk for bone and renal adverse effects among HIV-infected adolescents. Recent studies of CKD have focused primarily on estimating prevalence in different settings whereas studies of CLD are limited. SUMMARY: As perinatally HIV-infected children age into adolescence and adulthood with effective long-term ART, it is necessary to continue to evaluate their risks for noninfectious comorbidities and complications, understand mechanisms underlying their risks, and identify and evaluate interventions specifically in this population.

Cost-effectiveness of pre-exposure prophylaxis for HIV prevention in men who have sex with men in the UK: a modelling study and health economic evaluation.

BACKGROUND: In the UK, HIV incidence among men who have sex with men (MSM) has remained high for several years, despite widespread use of antiretroviral therapy and high rates of virological suppression. Pre-exposure prophylaxis (PrEP) has been shown to be highly effective in preventing further infections in MSM, but its cost-effectiveness is uncertain. METHODS: In this modelling study and economic evaluation, we calibrated a dynamic, individual-based stochastic model, the HIV Synthesis Model, to multiple data sources (surveillance data provided by Public Health England and data from a large, nationally representative survey, Natsal-3) on HIV among MSM in the UK. We did a probabilistic sensitivity analysis (sampling 22 key parameters) along with a range of univariate sensitivity analyses to evaluate the introduction of a PrEP programme with sexual event-based use of emtricitabine and tenofovir for MSM who had condomless anal sexual intercourse in the previous 3 months, a negative HIV test at baseline, and a negative HIV test in the preceding year. The main model outcomes were the number of HIV infections, quality-adjusted life-years (QALYs), and costs. FINDINGS: Introduction of such a PrEP programme, with around 4000 MSM initiated on PrEP by the end of the first year and almost 40 000 by the end of the 15th year, would result in a total cost saving (£1·0 billion discounted), avert 25% of HIV infections (42% of which would be directly because of PrEP), and lead to a gain of 40 000 discounted QALYs over an 80-year time horizon. This result was particularly sensitive to the time horizon chosen, the cost of antiretroviral drugs (for treatment and PrEP), and the underlying trend in condomless sex. INTERPRETATION: This analysis suggests that the introduction of a PrEP programme for MSM in the UK is cost-effective and possibly cost-saving in the long term. A reduction in the cost of antiretroviral drugs (including the drugs used for PrEP) would substantially shorten the time for cost savings to be realised. FUNDING: National Institute for Health Research.

[Cost-Fffectiveness of Two Antiviral Therapies for Chronic Hepatitis B in Peru: Entecavir and Tenofovir]. / Costo-efectividad de dos terapias antivirales para Hepatitis B crónica en el Perú: Entecavir y tenofovir.

OBJETIVES: To compare in terms of cost-effectiveness to entecavir (ETV) and tenofovir (TDF) in the treatment of hepatitis B virus (HBV) in public hospitals in Peru. MATERIALS AND METHODS: We structured a Markov model. We define effectiveness adjusted life years for quality (QALY). We include the direct costs of treatment in soles from the perspective of the Ministry of Health of Peru. We estimate the relationship between cost and effectiveness ratios (ICER). We performed sensitivity analyzes considering a range of willingness to pay (WTP) from one to three times the Gross Domestic Product (GDP) per capita, and a tornado analysis regarding Monetary Net Profit (BMN) or ICER. RESULTS: Treatment with TDF is more effective and less expensive than ETV. The ETV had a cost per QALY of PEN 4482, and PEN 1526 TDF. The PTO maintains a progressively larger with increasing WTP BMN. The discount rate was the only variable with a significant effect on model uncertainty. CONCLUSION: Treatment with TDF is more cost-effective than ETV in public hospitals in Peru.

OBJETIVOS: Comparar en términos de costo-efectividad a entecavir (ETV) y tenofovir (TDF) en el tratamiento del virus de la hepatitis B (HBV) en hospitales públicos del Perú. MATERIALES Y MÉTODOS: Estructuramos un modelo de Markov, definimos la efectividad en años de vida ajustados a calidad (AVAC). Incluimos los costos directos del tratamiento en soles desde la perspectiva del Ministerio de Salud del Perú. Calculamos la relación entre costo y efectividad incrementales (ICER). Realizamos análisis de sensibilidad determinístico y probabilístico, considerando un rango de disponibilidad de pago (WTP) desde uno hasta tres veces el producto bruto interno (PBI) per-cápita, y el beneficio monetario neto (BMN) o ICER en el caso del análisis de tornado. RESULTADOS: El tratamiento con TDF es más efectivo y menos costoso que ETV. El ETV tuvo un costo por AVAC de S/ 4482, y de S/ 1526 para TDF. El TDF mantiene un BMN progresivamente mayor conforme aumenta la WTP. La tasa de descuento fue la única variable con efecto significativo en la incertidumbre del modelo. CONCLUSIONES: El tratamiento con TDF es más costo-efectivo que ETV en hospitales públicos del Perú.

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.

Costo-efectividad de dos terapias antivirales para Hepatitis B crónica en el Perú: Entecavir y tenofovir / Cost-Fffectiveness of Two Antiviral Therapies for Chronic Hepatitis B in Peru: Entecavir and Tenofovir

RESUMEN Objetivos Comparar en términos de costo-efectividad a entecavir (ETV) y tenofovir (TDF) en el tratamiento del virus de la hepatitis B (HBV) en hospitales públicos del Perú. Materiales y métodos Estructuramos un modelo de Markov, definimos la efectividad en años de vida ajustados a calidad (AVAC). Incluimos los costos directos del tratamiento en soles desde la perspectiva del Ministerio de Salud del Perú. Calculamos la relación entre costo y efectividad incrementales (ICER). Realizamos análisis de sensibilidad determinístico y probabilístico, considerando un rango de disponibilidad de pago (WTP) desde uno hasta tres veces el producto bruto interno (PBI) per-cápita, y el beneficio monetario neto (BMN) o ICER en el caso del análisis de tornado. Resultados El tratamiento con TDF es más efectivo y menos costoso que ETV. El ETV tuvo un costo por AVAC de S/ 4482, y de S/ 1526 para TDF. El TDF mantiene un BMN progresivamente mayor conforme aumenta la WTP. La tasa de descuento fue la única variable con efecto significativo en la incertidumbre del modelo. Conclusiones El tratamiento con TDF es más costo-efectivo que ETV en hospitales públicos del Perú.

ABSTRACT Objetives To compare in terms of cost-effectiveness to entecavir (ETV) and tenofovir (TDF) in the treatment of hepatitis B virus (HBV) in public hospitals in Peru. Materials and methods We structured a Markov model. We define effectiveness adjusted life years for quality (QALY). We include the direct costs of treatment in soles from the perspective of the Ministry of Health of Peru. We estimate the relationship between cost and effectiveness ratios (ICER). We performed sensitivity analyzes considering a range of willingness to pay (WTP) from one to three times the Gross Domestic Product (GDP) per capita, and a tornado analysis regarding Monetary Net Profit (BMN) or ICER. Results Treatment with TDF is more effective and less expensive than ETV. The ETV had a cost per QALY of PEN 4482, and PEN 1526 TDF. The PTO maintains a progressively larger with increasing WTP BMN. The discount rate was the only variable with a significant effect on model uncertainty. Conclusion Treatment with TDF is more cost-effective than ETV in public hospitals in Peru.

Switching to a rilpivirine/emtricitabine/tenofovir single-tablet regimen in RNA-suppressed patients infected with human immunodeficiency virus 1: Effectiveness, safety and costs at 96 weeks.

OBJECTIVES: This study evaluates the effectiveness, safety and costs of switching to a rilpivirine/emtricitabine/tenofovir disoproxil fumarate (RPV/FTC/TDF) regimen in treatment-experienced HIV-1-infected patients with sustained virological suppression. METHODS: Observational, prospective study. Study population included all treatment-experienced patients with sustained virological suppression who switched to RPV/FTC/TDF during 2013 in a tertiary hospital. Patients were followed until they completed 96 weeks of treatment. The effectiveness end-point was defined as the proportion of patients who maintained virological suppression at week 96 by intention-to-treat analysis (discontinuation=failure). The safety of RPV/FTC/TDF (incidence of adverse events leading to discontinuation and laboratory abnormalities) and adherence to this regimen were evaluated, and the cost of switching was analysed. RESULTS: One-hundred forty-six patients were included. At week 96, 71.9% of patients remained virologically suppressed; 6.8% experienced virological failure. During follow-up, 25.3% of patients discontinued RPV/FTC/TDF (14.4% because of adverse events, mainly renal impairment). Throughout the 96 weeks, there were significant decreases in total cholesterol (TC) (14.0 mg/dL, P<.001), TC/HDL cholesterol ratio (0.4 mg/dL, P=.019) and triglycerides (42.0 mg/dL, P<.001). A slight decrease in glomerular filtration rate was observed (4.3 mL/min/1.73 m2 , P<.001). Switching to RPV/FTC/TDF improved adherence in the subgroup of patients whose previous treatment was based on a twice-daily schedule, although differences did not reach statistical significance. Switching to RPV/FTC/TDF reduced the annual per-patient antiretroviral cost by €1744 (P<.001). CONCLUSIONS: In virologically suppressed patients, the switch to a RPV/FTC/TDF regimen was associated with a mild but maintained improvement in lipid parameters and a significant reduction in costs. However, the relatively high rates of virological failure and treatment discontinuation because of adverse events make this combination a less favourable choice over other regimens currently available.

Cost-Effectiveness and Clinical Impact of Antiviral Strategies of HBeAg-Positive and -Negative Chronic Hepatitis B.

INTRODUCTION: Chronic hepatitis B (CHB) is associated with high burden and healthcare costs. Virologic response achieved with antivirals is associated with progression avoidance. This study aimed to estimate the efficiency and clinical impact of antiviral strategies in CHB patients. MATERIAL AND METHODS: A Markov model estimated lifetime complications and direct costs in both, HBeAg-positive and HBeAg-negative cohorts. Strategy 1 (71% of treated population) and strategy 2 (100%), both based on pegylated interferon (peg-IFN) followed by oral tenofovir or entecavir, were compared to no treatment. Progression was based on HBV-DNA levels. Rescue therapy with oral antivirals was applied for peg-IFN failure. Disease costs (C, 2014) and utilities were obtained from literature. RESULTS: Compared to natural history, strategy 1 increased QALY (3.98 in HBeAg-positive, 2.16 in -negative cohort). With strategy 2, survival was up to 5.60 (HBeAg-positive) and 3.05 QALY (in HBeAg-negative). The model predicted avoidance of 128 and 86 carcinomas in HBeAg-positive and -negative patients with strategy 1, and up to 181 and 121 in HBeAg-positive and -negative for strategy 2. Total cost increased up to C102,841 (strategy 1) and C105,408 (strategy 2) in HBeAg-positive, and C85,858 and C93,754 in HBeAg-negative. A C1,581/QALY gained ratio was estimated versus the natural history for both strategies. In conclusion, increasing antiviral coverage would be efficient, reducing complications.

Economic Analysis and Budget Impact of Tenofovir and Entecavir in the First-Line Treatment of Hepatitis B Virus in Italy.

BACKGROUND: Chronic hepatitis B is a common, progressive disease, particularly when viral replication is detected. Oral antivirals can suppress viral replication and prevent or delay the development of cirrhosis and liver-related complications. The treatments of chronic hepatitis B cannot totally cure the disease but can prevent its progression to hepatocellular carcinoma, decreasing the levels of both morbidity and mortality. To date, there are several therapies indicated by the international guidelines as first-line treatments for the management of hepatitis B; two of the most effective are those based on either tenofovir or entecavir. OBJECTIVE: The aim of this study is to evaluate the cost-effectiveness of tenofovir and entecavir in the treatment of naïve patients with chronic hepatitis B. The two treatments are compared with the "no treatment" and to one another. METHODS: The cost-effectiveness analysis was conducted using a Markov model; patients entered one of the following health states: chronic hepatitis, cirrhosis (compensated or decompensated), hepatocellular carcinoma, liver transplantation or death. The analysis was carried out from the perspective of the Italian National Health Service by considering a life-time horizon with cycles lasting 1 year and with costs and QALYs (quality-adjusted life years) discounted at a rate of 3.5%. The results of the model were analysed in terms of incremental cost-effectiveness ratio (ICER). RESULTS: ICERs for tenofovir and entecavir emerging from the comparison versus "no treatment" were equal to €10,274.73 and €16,300.44 per QALY gained, respectively, on the life-time horizon. Tenofovir was dominant in the direct comparison with entecavir, indicating more QALYs and a lower consumption of resources. The Monte Carlo simulation demonstrated that in 97% (tenofovir) and in 85% (entecavir) of the scenarios performed, the cost per QALY fell below the threshold of €30,000/QALY. The budget impact analysis showed savings for tenofovir amounting to 33% compared to entecavir in the first year on treatment and to 31% in following years. CONCLUSIONS: Entecavir and tenofovir are recommended for the treatment of patients with chronic Hepatitis B in the Italian Health System. In particular, tenofovir appeared to be the more cost-effective drug for the management of chronic hepatitis B virus (HBV) infections. These results could help decision makers and clinicians to address their decision when choosing a first-line treatment for the management of people affected by chronic HBV.