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Purpose: A comprehensive study comparing the costs and efficacies of darunavir/ritonavir 800/100 mg qd and the other ritonavir-boosted (/r) protease inhibitors (PIs) recommended for treatment-naïve individuals with HIV-1 infection would help health care decision makers identify the value of each boosted PI., Methods: A cost-efficacy model was developed to compare the five recommended boosted PIs, each used with a tenofovir-based nucleotide/nucleoside reverse transcriptase inhibitor backbone. Efficacy was measured by virologic response (ie, HIV-1 ribonucleic acid < 50 copies/mL) at 48 weeks, based on a systematic review and meta-analysis of recent clinical trials. One-year antiretroviral therapy costs and 48-week efficacy values were used to generate the efficiency frontier and cost-efficacy ratios., Results: Darunavir/r was the most efficacious boosted PI, with an incremental cost-efficacy ratio of $27,390 per additional individual with virologic response, compared with fosamprenavir/r. All other regimens were dominated. Darunavir/r combination therapy also had one of the lowest average costs ($26,287) per individual with virologic response, resulting in a maximal number of individuals successfully treated within a fixed budget. The model results were robust in variability and sensitivity analyses., Conclusion: Darunavir/r 800/100 mg qd combination therapy represents a cost-efficacious option for treatment-naïve individuals with HIV-1 infection in the United States.

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.

Background: Given the association between CD4 cell counts and HIV-related morbidity/mortality, new antiretroviral therapies could potentially lower the direct costs of HIV care by raising CD4 cell counts., Objectives: To predict the effects of the ritonavir-boosted, HIV protease inhibitor (PI) darunavir on the direct costs of care, while accounting for CD4 cell counts, during the first year of therapy in highly treatment-experienced, HIV-infected adults in different healthcare settings., Methods: The mean annual per-patient cost of darunavir/ritonavir (DRV/r) and control PI-based highly active antiretroviral therapy (HAART) was calculated from the proportional use of antiretroviral agents in the DRV/r and control PI arms of the pooled POWER 1 and 2 trials, applying drug-acquisition costs for five healthcare settings. Non-antiretroviral-related costs by CD4 cell count, derived from non-interventional studies in the same settings, were applied to the POWER data (proportion of patients with CD4 cell counts in different strata at week 48) to estimate mean annual non-antiretroviral-related costs per patient in patients receiving DRV/r or control PI-based HAART during year 1., Results: Across all settings, the mean annual per-patient cost of DRV/r-based treatment was 2-19% higher than that of control PI-based therapy during the first year of therapy. By raising CD4 cell counts, however, DRV/r-based regimens were predicted to lower mean annual non-antiretroviral-related costs by 16-38% compared with control PI-based therapy. When combined, the total annual per-patient cost of HIV care during the first year of therapy was estimated to be 7% lower in the DRV/r compared with the control PI arm using US data, 8% lower using Swedish data, budget neutral using UK and Belgian data and 5% higher using Italian data., Conclusions: Darunavir-based HAART may lower non-antiretroviral-related costs compared with control PI-based therapy in highly treatment-experienced, HIV-infected patients during the first year of therapy by improving patients' CD4 cell counts. These costs could partly/fully offset the increased acquisition cost of DRV/r in this patient population over the same period.

Introduction: 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., Methods: 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., Results: 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., Conclusion: 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.

Objective: to determine if there are sex differences in physician burnout in the Netherlands and, if not, to explore why they are present in the United States., Methods: Separate physician surveys were conducted in the United States (n=2326) and the Netherlands (n=1426). Thirty-three percent of US respondents were female (adjusted response rate 52%); 18% of Dutch respondents were female (adjusted response rate 63%). Standardized mean sex differences (effect sizes) in burnout variables were calculated and compared crossnationally., Results: US women experienced more burnout than US men did (28% v 21%, p<.01), but the sex difference in burnout among Dutch physicians was not significant. Women in both countries worked fewer hours than men did (48 v 56 US, 44 v 56 NL, difference in effect sizes of sex differences between US and NL, p<.001). Although women in both countries described less work control than men, the effect size of the sex difference in the United States was more than twice that in the Netherlands (.34 US v .15 NL, p<.01). Children, home support, and work-home interference were comparable between sexes in the United States., Conclusions: Gender parity in physician burnout in the Netherlands may be due to fewer work hours and greater work control of women compared to those in the United States.