Background: 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). Objective: 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. Methods: 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/mm) 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. Results: 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 &U20AC;11 438/QALY in Belgium, &U20AC;12 122/QALY in Italy, &U20AC;10 942/QALY in Sweden and &U20AC;16 438/QALY in the UK. Assuming an acceptability threshold of &U20AC;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. Conclusion: 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.
