Introduction: 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.
Methods: 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.
Results: 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.
Conclusions: 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.