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: Abstract Background Guidelines from the Department of Health and Human Sciences in the United States (US) recommend ritonavir-boosted lopinavir (LPV/r) as a preferred protease inhibitor (PI) for HIV-positive antiretroviral-naїve pregnant women. These guidelines also cite ritonavir-boosted darunavir (DRV+RTV) as an alternative PI in this clinical scenario. The purpose of this analysis was to compare economic outcomes for regimens based on these two treatments. Study Design An existing discrete event simulation (DES) model was adapted to conduct a cost-minimization analysis comparing the two regimens in HIV-infected women of childbearing age (WOCBA), from the perspective of a healthcare payer in the United States. Methods The DES model was used to represent disease states, health events, healthcare encounters, pregnancy and treatment choices in HIV-infected WOCBA starting treatment with regimens based on either LPV/r or DRV+RTV. It also incorporated parameters for individual patient characteristics, and for antiretroviral (ARV) treatment effectiveness, treatment sequencing, clinical progression and resource use. Potential events included scheduled physician visits; viral suppression; viral rebound; AIDS-related complications; CHD events; treatment discontinuation and switching; ARV treatment side effects (SE); and death. The primary outcomes were discounted 5-year and 10-year healthcare costs. Alternative scenarios considered different rates of switching from DRV+RTV to LPV/r upon conception. Results Compared with DRV+RTV, LPV/r was associated with similar clinical outcomes while offering savings at the 5- and 10-year horizons (of $24,904 and $43,502 per patient, respectively), and in extensive sensitivity analyses. The main driver of the savings was the difference in cost between PIs. Conclusions Starting HIV-infected ARV-treatment-naїve WOCBA on an LPV/r-based regimen is cost-saving and provides similar patient outcomes compared to a DRV+RTV-based regimen.Journal of Medical Economics 12/2013;
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ABSTRACT: The latest HIV-1 protease inhibitor (PI) darunavir (Prezista™) has a high genetic barrier to resistance development and is active against wild-type HIV and HIV strains no longer susceptible to some older PIs. Ritonavir-boosted darunavir, as a component of antiretroviral therapy (ART), is indicated for the treatment of HIV-1 infection in adult and paediatric patients (aged ≥3 years), with or without treatment experience (details vary depending on region of approval). Several open-label or partially-blinded trials have evaluated the efficacy of ritonavir-boosted darunavir ART regimens for up to 192 weeks in these settings. In treatment-naïve adults, once-daily boosted darunavir was no less effective in establishing virological suppression than once- or twice-daily boosted lopinavir, yet was more effective at maintaining suppression long term. Moreover, treatment-experienced adults with no darunavir resistance-associated mutations (RAMs) had no less effective viral load suppression with once-daily than with twice-daily boosted darunavir. In treatment-experienced adults, including some with multiple major PI RAMs, twice-daily boosted darunavir was more effective than twice-daily boosted lopinavir or boosted control PIs in reducing viral load, and provided virological benefit as part of a salvage regimen in those with few remaining treatment options. Boosted darunavir also reduced viral load when administered once-daily in treatment-naïve adolescents or twice-daily in treatment-experienced children and adolescents. Boosted darunavir is generally well tolerated, with gastrointestinal disturbances and lipid abnormalities among the most common tolerability issues. It has a lipid profile more favourable than that of boosted lopinavir in terms of total cholesterol and triglyceride changes and, when administered once daily, its lipid effects are generally similar to those of boosted atazanavir. Thus, boosted darunavir is a useful option for the ART regimens of adult and paediatric patients with HIV-1 infection.Drugs 12/2013; · 4.13 Impact Factor
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ABSTRACT: The AntiRetroviral Therapy with TMC114 ExaMined In naive Subjects (ARTEMIS) clinical trial examined the efficacy and safety of two ritonavir-boosted protease inhibitors (PI/r), darunavir/r 800/100 mg once daily (QD) and lopinavir/r 800/200 mg daily, both used in combination with tenofovir disoproxil fumarate/emtricitabine. This study aimed to assess the cost effectiveness of the darunavir/r regimen compared with the lopinavir/r regimen in treatment-naive adults with HIV-1 infection in Canada.PharmacoEconomics 06/2014; · 3.34 Impact Factor