Cost effectiveness of darunavir/ritonavir in highly treatment-experienced, HIV-1-infected adults in the USA.
ABSTRACT Darunavir is a new protease inhibitor (PI) that is co-administered with low-dose ritonavir and has demonstrated substantial efficacy in clinical trials of highly treatment-experienced patients when combined with an optimized background regimen (with or without enfuvirtide). This study estimates the cost effectiveness of darunavir with ritonavir (DRV/r) in this population over 5-year and lifetime time horizons in the USA.
A Markov model was used to follow a treatment-experienced HIV-1 cohort through six health states, based on CD4 cell count: greater than 500, 351-500, 201-350, 101-200, 51-100 and 0-50 cells/mm³, and death. The magnitude of the CD4 cell count increase and duration of increasing and stable periods were derived from week 48 DRV/r clinical trial results (POWER 1 and 2). The treatment pathway assumed one regimen switch following treatment failure on the initial regimen. The use of antiretroviral drugs was based on usage in DRV/r clinical trials. US daily wholesale acquisition costs were calculated using the recommended daily doses. For each CD4 cell count range, utility values, HIV-1-related mortality rates and costs for medical resources (other than antiretroviral drug costs) were obtained from published literature. Non-HIV-1-related mortality rates were calculated by applying a relative risk value to the US general population age and gender-specific mortality rates. Costs and outcomes were discounted at 3% per year. One-way and probabilistic sensitivity analyses and variability analysis were performed.
In a 5-year analysis, patients receiving DRV/r experienced 3.80 quality-adjusted life-years (QALYs) and incurred total medical costs of US$217,288, while those receiving control PIs experienced 3.60 QALYs and incurred costs of US$218,962. DRV/r was both more effective and less costly than control PIs. For the lifetime analysis, the QALYs and lifetime medical costs with DRV/r were 10.03 and US$565,358, compared with 8.76 and US$527,287 with control PIs. The incremental cost-effectiveness ratio for DRV/r compared with control PIs was US$30,046. One-way sensitivity analyses for both time horizons indicated that the results were most sensitive to changes in the rate of CD4 cell count change during stable and declining periods (lifetime only), duration of stable period (5-year only) and HIV-1-related mortality rates. The results of the variability analysis were most sensitive to the model time horizon. Nevertheless, for all ranges and scenarios tested in these analyses, the incremental cost per QALY gained remained below US$50,000. The probabilistic sensitivity analysis showed that there was a 0.921 and 0.950 probability of a cost-effectiveness ratio below US$50,000 per QALY for the 5-year and lifetime time horizon, respectively.
DRV/r is predicted to be cost effective compared with control PI in highly treatment-experienced patients and is predicted to yield an average of 0.20 additional QALYs per treatment-experienced patient over 5 years and 1.27 additional QALYs over a lifetime in this population.
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ABSTRACT: To assess the cost-effectiveness of etravirine (INTELENCE), a novel nonnucleoside reverse transcriptase inhibitor, used in combination with a background regimen that included darunavir/ritonavir, from a Canadian Provincial Ministry of Health perspective. A Markov model with a 3-month cycle time and six health states based on CD4 cell count ranges was developed to follow a hypothetical cohort of treatment-experienced adults with HIV-1 infection through initial and subsequent treatment regimens. Costs (in 2009 Canadian dollars), utilities, and HIV-related mortality data for each health state as well as non-HIV-related mortality data were estimated from Canadian sources and published literature. Transition probabilities between health states and first-year hospitalization and mortality rates were derived from clinical trial data. Incremental 1-year costs per additional adult with viral load less than 50 copies/ml at 48 weeks and incremental lifetime costs per quality-adjusted life-year (QALY) gained were estimated using a 5% discount rate. Sensitivity and variability analyses and model validation were performed. Etravirine was associated with an increased probability of achieving less than 50 copies/ml at 48 weeks of 0.205 and an estimated gain of 0.66 discounted (1.48 undiscounted) QALYs over a lifetime. The incremental 1-year cost per additional person with viral load less than 50 copies/ml was $23,862. The lifetime incremental cost per QALY gained was $49,120. For the uncertainty ranges and variability scenarios tested for the lifetime horizon, the cost-effectiveness ratio was between $28,859 and 66,249. When compared with optimized standard of care including darunavir/ritonavir, adding etravirine represents a cost-effective option for treatment-experienced adults in Canada.AIDS (London, England) 11/2011; 26(3):355-64. DOI:10.1097/QAD.0b013e32834e87e6 · 6.56 Impact Factor
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ABSTRACT: The aim of this article was to perform a detailed methodological review of models used to estimate the cost effectiveness of drug treatment regimens for HIV infection in Europe and North America and assess the relationship between the different modeling approaches or key structural assumptions and the results. Electronic searches in three databases (MEDLINE, EMBASE, and the Cochrane Library) identified the cost-effectiveness models. Modeling approaches and structural assumptions were abstracted for all models. For three case studies of multiple analyses that compared the cost effectiveness of two drug regimens using the same clinical data inputs, differences in results were compared with differences in modeling approaches and structural assumptions. Forty-one model publications were reviewed. Recent models included Monte Carlo simulations, Markov models, or discrete-event simulation models, all including multiple lines of therapy and capturing the long-expected duration of efficacy of highly active antiretroviral therapy. In the three case studies, assumptions about the duration of efficacy after the trial time period, whether differences between the two regimens persist after the trial time period, the sequence of regimens after initial regimen failure, and the cost and utility assigned to adverse events, but not the modeling approach, were the most important factors in explaining differences in the results. As the models and treatment pathways get more complex, models should be validated using clinical trial data and local observational databases. The results of sensitivity analyses testing the impact of the structural assumptions that might change the results as identified in this review should also be presented in modeling papers.PharmacoEconomics 11/2013; 31(11). DOI:10.1007/s40273-013-0098-6 · 3.34 Impact Factor
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ABSTRACT: OBJECTIVES: To assess the virologic and immunological response of darunavir/ritonavir plus optimized background therapy in highly antiretroviral-experienced HIV-infected patients in Brazil. METHODS: Prospective cohort study carried out in a tertiary center in Sao Paulo, Brazil. Three-class antiretroviral-experienced patients with confirmed virologic failure began darunavir/ritonavir plus optimized background therapy (nucleoside/tide reverse transcriptase inhibitors±raltegravir±enfuvirtide±maraviroc) after performing a genotypic resistance assay. Clinical evaluation and laboratory tests were collected at baseline and at weeks 12, 24, and 48. Multivariate analysis was performed to identify predictors of virologic response at 48 weeks. RESULTS: Ninety-two patients were included. The median of darunavir resistant mutation was 1 (range 0-6). The median genotypic sensitivity score in the optimized background therapy was 2 (interquartile range 1-2). At week 48, 83% (95% CI: 75-90%) had an HIV RNA level <50 copies/mL and the median CD4 cell count was 301 (interquartile range 224-445) cells/mm(3). Baseline HIV RNA >100000 copies/mL was inversely associated with virologic success at week 48 (HR: 0.22, 95% CI: 0.06-0.85, p=0.028). CONCLUSIONS: Darunavir/ritonavir plus optimized background therapy was a highly effective salvage regimen under clinical routine conditions in a referral center in Brazil, which is similar to the reported in high-income countries.The Brazilian journal of infectious diseases: an official publication of the Brazilian Society of Infectious Diseases 01/2013; DOI:10.1016/j.bjid.2012.08.022 · 1.10 Impact Factor