The cost-effectiveness of testing for NS5a resistance-associated polymorphisms at baseline in genotype 1a-infected (treatment-naïve and treatment-experienced) subjects treated with all-oral elbasvir/grazoprevir regimens in the United States.

BACKGROUND: The presence of baseline NS5A resistance-associated variants (RAVs) impacted treatment response in HCV genotype 1a (GT1a)-infected patients treated with elbasvir/grazoprevir (EBR/GZR) for 12 weeks, but not patients treated with EBR/GZR and ribavirin (RBV) for 16 weeks. AIMS: To assess the cost-effectiveness of baseline testing for NS5A RAVs in EBR/GZR-treated patients compared without testing, and with current treatments for GT1a patients. METHODS: We simulated the course of treatment with EBR/GZR, ledipasvir/sofosbuvir (LDV/SOF) and ombitasvir/paritaprevir/ritonavir+dasabuvir (3D) with or without RBV and natural history of disease of GT1a patients. Treatment-related data from clinical trials were used in a state-transition model of the natural history of chronic HCV GT1a infection and liver disease to project lifetime costs (US$2015) and quality-adjusted life years (QALY). Other clinical and economic inputs were estimated from published sources. We conducted base case and sensitivity analyses. RESULTS: RAVs testing-guided treatment with EBR/GZR resulted in more QALYs than EBR/GZR without testing, 3D+RBV, or LDV/SOF8. This strategy was cost-saving relative to 3D+RBV or LDV/SOF8 and was cost-effective compared with EBR/GZR without testing. LDV/SOF12 was not cost-effective compared with the EBR/GZR RAVs testing-based strategy. Treatment with EBR/GZR guided by RAVs testing is the most effective regimen among treatment-experienced patients without cirrhosis and cirrhotic patients. In sensitivity analysis, RAVs testing was cost-effective in 48-55% and 63-85% among noncirrhotic and cirrhotic patients respectively. CONCLUSIONS: RAVs testing before treatment with EBR/GZR is likely to be a cost-effective alternative to the use of EBR/GZR without testing, LDV/SOF, or 3D among GT1a treatment-naïve or treatment-experienced patients.

Differential characteristics of primary infection and re-infection can cause backward bifurcation in HCV transmission dynamics.

Backward bifurcation, a phenomenon typically characterized by the co-existence of multiple stable equilibria when the associated reproduction number of the model is less than unity, has been observed in numerous disease transmission models. This study establishes, for the first time, the presence of this phenomenon in the transmission dynamics of hepatitis C virus (HCV) within an IDU population. It is shown that the phenomenon does not exist under four scenarios, namely (i) in the absence of re-infection, (ii) in the absence of differential characteristics of HCV infection (with respect to infectivity, progression, treatment and recovery) between re-infected individuals and primary-infected individuals, (iii) when re-infected and treated individuals do not transmit HCV infection and (iv) when the average infectivity-adjusted duration of re-infection is less than that of primary infection. This study identifies, using sensitivity analysis, five parameters of the model that have the most influence on the disease transmission dynamics, namely: effective contact rate, progression rate from acute to chronic infection, recovery rate from acute infection, natural death rate and the relative infectiousness of chronically-infected individuals. Numerical simulations of the model show that the re-infection of recovered individuals has marginal effect on the HCV burden (as measured in terms of the cumulative incidence and the prevalence of the disease) in the IDU community. Furthermore, treatment of infected IDUs, even for small rate (such as 4%), offers significant impact on curtailing HCV spread in the community.

The epidemiological and economic impact of a quadrivalent human papillomavirus vaccine (6/11/16/18) in the UK.

OBJECTIVE: To assess the potential epidemiological and economic impact of a prophylactic quadrivalent human papillomavirus (HPV) (6/11/16/18) vaccine for preventing cervical cancer, cervical intraepithelial neoplasia grades 2 and 3 (CIN2/3), CIN1 and genital warts. DESIGN: Cost-utility analysis. SETTING: UK. POPULATION: Female and male UK population 12 years or older. METHODS: We adapted a previously developed multi-HPV type dynamic transmission to compare four female vaccination strategies, routine vaccination at age 12 years, and routine vaccination at age 12 years combined with temporary catch-up vaccination at ages 12-14, 12-17 and 12-24 years. MAIN OUTCOMES MEASURES: Costs, cases avoided, incremental cost per quality-adjusted life year (QALY). RESULTS: The model projected that at year 100, each vaccination strategy could reduce the number of HPV 6/11/16/18-related cervical cancer, CIN2/3, CIN1 and genital wart cases among women by 86, 85, 79 and 89% respectively. Over 25 years, routine vaccination at age 12 years combined with a 12- to 24-year-old catch-up programme was the most effective strategy, reducing the cumulative number of cases of cervical cancer, CIN2/3, CIN1 and genital warts by 5800, 146 000, 28 000, and 1.1 million respectively. Over 100 years, the incremental cost-effectiveness ratios across all strategies ranged from pound5882 to pound11,412 per QALY gained. CONCLUSION: In the UK, a quadrivalent HPV vaccination programme that includes a catch-up strategy can reduce the incidence of cervical cancer, CIN and genital warts at a cost per QALY ratio within the range typically regarded as cost-effective.

Role of incidence function in vaccine-induced backward bifurcation in some HIV models.

The phenomenon of backward bifurcation in disease models, where a stable endemic equilibrium co-exists with a stable disease-free equilibrium when the associated reproduction number is less than unity, has important implications for disease control. In such a scenario, the classical requirement of the reproduction number being less than unity becomes only a necessary, but not sufficient, condition for disease elimination. This paper addresses the role of the choice of incidence function in a vaccine-induced backward bifurcation in HIV models. Several examples are given where backward bifurcations occur using standard incidence, but not with their equivalents that employ mass action incidence. Furthermore, this result is independent of the type of vaccination program adopted. These results emphasize the need for further work on the incidence functions used in HIV models.

Discrete time representation of the formula for calculating DALYs.

The global burden of disease (GBD) was measured using a new indicator called disability-adjusted life years (DALYs). The formula to calculate DALYs is based on the idea of time being a continuous variable, which is not consistent with the way economic and health data are collected and reported, and is also different from the concept of time used in the vast majority of policy analyses. Use of this formula gives rise to a time-aggregation bias in the estimates of GBD. Based on discrete time representation and the key principles outlined in the GBD study, a new formula for estimating DALYs is derived in this paper. The properties of the two formulae are compared and contrasted and the implications of using the new formula are discussed. The results show that there is an appreciable difference in percentage terms (14.06%) between the burden of cataract in Sub-Saharan Africa in 1990 calculated using the new and the old formulae. The global burden of diseases and injuries as previously reported in the GDB study may, therefore, be underestimated and the relative positions of some diseases and injuries, and hence the relative priorities of related interventions, may shift if the more appropriate, discrete-time formula is used. The difference is greatest for diseases of short duration (e.g. infectious diseases).

Costs and benefits of a subtype-specific surveillance system for identifying Escherichia coli O157:H7 outbreaks.

We assessed the societal costs and benefits of a subtype-specific surveillance system for identifying outbreak-associated Escherichia coli O157:H7 infections. Using data from Colorado, we estimated that if it averted five cases annually, the system would recover all its costs.