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: BACKGROUND: The ARTEMIS trial compared first-line antiretroviral therapy (ART) with lopinavir/ritonavir (LPV/r) to darunavir plus ritonavir (DRV + RTV) for HIV-1-infected subjects. In order to fully assess the implications of this study, economic modelling extrapolating over a longer term is required. OBJECTIVE: The aim of this study was to simulate the course of HIV and its management, including the multiple factors known to be of importance in ART. METHODS: A comprehensive discrete event simulation was created to represent, as realistically as possible, ART management and HIV outcomes. The model was focused on patients for whom clinicians believed that LPV/r or DRV + RTV were good options as a first regimen. Prognosis was determined by the impact of initial treatment on baseline CD4+ T-cell count and viral load, adherence, virological suppression/failure/rebound, acquired resistance mutations, and ensuing treatment changes. Inputs were taken from trial data (ARTEMIS), literature and, where necessary, stated assumptions. Clinical measures included AIDS events, side effects, time on sequential therapies, cardiovascular events, and expected life-years lost as a result of HIV infection. The model underwent face, technical and partial predictive validation. Treatment-naive individuals similar to those in the ARTEMIS trial were modelled over a lifetime, and outcomes with first-line DRV + RTV were compared with those with LPV/r, both paired with tenofovir and emtricitabine. Up to three regimen changes were permitted. Drug prices were based on wholesale acquisition cost. Outcomes were lifetime healthcare costs (in 2011 US dollars) from the US healthcare system perspective and quality-adjusted life-years (QALYs) (discounted at 3 % per annum). RESULTS: Choice of LPV/r over DRV + RTV as initial ART resulted in nearly identical clinical outcomes, but distinctly different economic consequences. Starting with an LPV/r regimen potentially results in approximately US$25,000 discounted lifetime savings. Accumulated QALYs for LPV/r and DRV + RTV were 12.130 and 12.083, respectively (a 19-day difference). In sensitivity analyses, net monetary benefit ranged from US$12,000 to US$31,000, favouring LPV/r (base case US$27,762). CONCLUSIONS: A comprehensive simulation of lifetime course of HIV in the USA indicated that using LPV/r as first-line therapy compared with DRV + RTV may result in cost savings, with similar clinical outcomes.PharmacoEconomics 04/2013; · 2.86 Impact Factor
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ABSTRACT: Two phase II trials (POWER 1 and 2) have demonstrated that darunavir co-administered with low-dose ritonavir (DRV/r) provides significant clinical benefit compared with control protease inhibitors (PIs) in highly treatment-experienced, HIV-1-infected adults, when co-administered with optimized background therapy (OBR). To determine whether DRV/r is cost effective compared with control PIs, from the perspective of Belgian, Italian, Swedish and UK reimbursement authorities, when used in treatment-experienced patients similar to those included in the POWER 1 and 2 trials. An existing Markov model containing health states defined by CD4 cell count ranges (> 500, 351-500, 201-350, 101-200, 51-100 and 0-50 cells/mm³) and death was adapted for use in four European healthcare settings. Baseline demographics, CD4 cell count distribution and antiretroviral drug usage reflected those reported in the POWER 1 and 2 trials. Virological/immunological response rates and matching transition probabilities over the patient's lifetime were based on results from the POWER trials and published data. After treatment failure, patients were assumed to switch to a tipranavir-containing regimen plus OBR. For each CD4 cell count range, utility values and HIV-related mortality rates were obtained from the published literature. National all-cause mortality data and published data on the increased risk of non HIV-related mortality in HIV-infected individuals were taken into account in the model. Data from observational studies conducted in each healthcare setting were used to determine resource-use patterns and costs associated with each CD4 cell count range. Unit costs were derived from official local sources; a lifetime horizon was taken and discount rates were selected based on local guidelines. In the base-case analysis, quality-adjusted life-year (QALY) gains of up to 1.397 in Belgium, over 1.171 in Italy, 1.142 in Sweden and 1.091 in the UK were predicted when DRV/r-based therapy was used instead of control PI-based treatment. The base-case analyses predicted an incremental cost-effectiveness ratio (ICER) of €11,438/QALY in Belgium, €12,122/QALY in Italy,€10,942/QALY in Sweden and €16,438/QALY in the UK. Assuming an acceptability threshold of €30,000/QALY, DRV/r-based therapy remained cost effective over all parameter ranges tested in extensive one-way sensitivity analyses. Probabilistic sensitivity analysis revealed a 95% (Belgium), 97% (Italy), 92% (Sweden) or 78% (UK) probability of attaining an ICER below this threshold. From four European payer perspectives, DRV/r-based antiretroviral therapy is predicted to be cost effective compared with currently available control PIs, when both are used with an OBR in treatment-experienced, HIV-1-infected adults who failed to respond to more than one PI-containing regimen.PharmacoEconomics 12/2010; 28 Suppl 1:107-28. · 2.86 Impact Factor
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ABSTRACT: The phase III TITAN trial evaluated the use of darunavir with low-dose ritonavir (DRV/r) 600/100 mg twice daily (bid) compared with lopinavir with low-dose ritonavir (LPV/r) in treatment-experienced, lopinavir-naive patients. This study estimates the cost effectiveness of DRV/r from a US societal perspective when compared with LPV/r in treatment-experienced patients with a profile similar to those TITAN patients who had one or more International AIDS Society - USA (IAS-USA) primary protease inhibitor (PI) resistance-associated mutations (RAMs) at baseline. This population had less advanced HIV disease and a broader range of previous PI exposure/failure (0 - ≥ 2 PIs) at enrollment than those in the darunavir phase IIb POWER trials. An existing Markov model containing six health states defined by CD4 cell count range (>500, 351-500, 201-350, 101-200, 51-100 and 0-50 cells/mm³) and an absorbing state of death was adapted. Baseline demographics, CD4 cell count distribution and antiretroviral drug usage, virological response (at week 24), and immunological response estimates and matching transition probabilities were based on data collected directly from the one or more IAS-USA PI mutation subpopulation during the first 48 weeks of the TITAN trial, as well as from published literature. Patients were assumed to switch to a regimen containing tipranavir plus an optimized background regimen after treatment failure. For each CD4 cell count range or health state, the utility values, HIV and non-HIV-related mortality rates, and non-antiretroviral-related cost of HIV care estimates were derived from published literature. Unit costs were derived from official local sources. A lifetime horizon was taken in the base-case analysis. The base-case analysis predicted discounted quality-adjusted survival gains of 0.493 quality-adjusted life-years (QALYs) for DRV/r compared with LPV/r, resulting in an incremental cost-effectiveness ratio (ICER) of US$23,057 per QALY gained over a lifetime horizon. Probabilistic sensitivity analysis indicated a 0.754 probability of an ICER below the threshold of US$50,000 per QALY gained. DRV/r remained cost effective over all parameter ranges tested in extensive one-way sensitivity analyses and variability analyses, which examined the impact of input parameter uncertainty and changes in model assumptions and treatment patterns, respectively. Shortening the model time horizon had the largest impact on the ICER, reducing it most notably to US$4919 with a 10-year time horizon. From a US societal perspective and based on an analysis of the patients with primary IAS-USA PI RAMs enrolled in the darunavir phase III TITAN trial, a highly active antiretroviral therapy (HAART) regimen containing DRV/r 600/100 mg bid is estimated to be a cost-effective therapy when compared with a HAART regimen containing LPV/r, for the management of treatment-experienced, PI-resistant, HIV-infected adults with a broad range of previous PI use/failure.PharmacoEconomics 12/2010; 28 Suppl 1:129-46. · 2.86 Impact Factor