Cost Effectiveness of Darunavir/Ritonavir in Highly Treatment-Experienced, HIV-1-Infected Adults in the USA

RTI Health Solutions, Research Triangle Park, North Carolina, USA.
PharmacoEconomics (Impact Factor: 2.45). 12/2010; 28 Suppl 1(suppl 1):83-105. DOI: 10.2165/11587470-000000000-00000
Source: PubMed


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: Darunavir boosted by low-dose ritonavir (DRV/r), at a daily dose of 600/100mg twice a day (bid), has been shown to be superior to alternative highly active antiretroviral therapy (HAART) regimens for the management of treatment-experienced, HIV-infected adults in the phase IIb POWER trials and the phase III TITAN trial. Economic analyses of different types that have been performed for several countries to investigate the cost effectiveness and budgetary impact of DRV/r 600/100mg bid for treatment-experienced people living with HIV (PLHIV) based on the clinical data gathered in the POWER and TITAN trials are reviewed for consistency and their value to different decision-makers is assessed. Cost-utility analyses for the USA and several European countries indicate that DRV/r-based HAART is cost effective compared with other standard of care protease inhibitor (PI)-based regimens in PLHIV with evidence of PI resistance. For all of these countries, the estimated cost-utility ratio is well below typical benchmark values and these ratios are robust, as demonstrated by one-way sensitivity and variability analyses and multi-way probabilistic sensitivity analyses. Studies using other metrics including the average 1-year drug cost per patient with a plasma HIV-RNA level less than 50 copies/mL at 48 weeks, the incremental drug cost per additional patient with a plasma HIV-RNA level less than 50 copies/mL at 48 weeks, the total (antiretroviral and nonantiretroviral) costs during the first year of treatment, and the total healthcare budget impact during the first 5 years of treatment provided further evidence of the positive economic outcomes with the use ofDRV/r in treatmentexperienced PLHIV. Different measures of economic outcomes are useful for different types of decision-makers and different types of decisions. In general, the results of these different types of analyses will be consistent with each other. For darunavir, the economic analyses reviewed in this paper demonstrate that the use of DRV/r 600/100mg bid in the management of HIV-infected, treatmentexperienced adults who have failed at least one of the other currently available PIs is cost effective and may be cost saving.
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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.
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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.
    No preview · Article · Dec 2010 · PharmacoEconomics
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