Cost-effectiveness of adding bedaquiline to drug regimens for the treatment of multidrug-resistant tuberculosis in the UK.

OBJECTIVE: To evaluate the cost-effectiveness of adding bedaquiline to a background regimen (BR) of drugs for multidrug-resistant tuberculosis (MDR-TB) in the United Kingdom (UK). METHODS: A cohort-based Markov model was developed to estimate the incremental cost-effectiveness ratio of bedaquiline plus BR (BBR) versus BR alone (BR) in the treatment of MDR-TB, over a 10-year time horizon. A National Health Service (NHS) and personal social services perspective was considered. Cost-effectiveness was evaluated in terms of Quality-Adjusted Life Years (QALYs) and Disability-Adjusted Life Years (DALYs). Data were sourced from a phase II, placebo-controlled trial, NHS reference costs, and the literature; the US list price of bedaquiline was used and converted to pounds (£18,800). Costs and effectiveness were discounted at a rate of 3.5% per annum. Probabilistic and deterministic sensitivity analysis was conducted. RESULTS: The total discounted cost per patient (pp) on BBR was £106,487, compared with £117,922 for BR. The total discounted QALYs pp were 5.16 for BBR and 4.01 for BR. The addition of bedaquiline to a BR resulted in a cost-saving of £11,434 and an additional 1.14 QALYs pp over a 10-year period, and is therefore considered to be the dominant (less costly and more effective) strategy over BR. BBR remained dominant in the majority of sensitivity analyses, with a 81% probability of being dominant versus BR in the probabilistic analysis. CONCLUSIONS: In the UK, bedaquiline is likely to be cost-effective and cost-saving, compared with the current MDR-TB standard of care under a range of scenarios. Cost-savings over a 10-year period were realized from reductions in length of hospitalization, which offset the bedaquiline drug costs. The cost-benefit conclusions held after several sensitivity analyses, thus validating assumptions made, and suggesting that the results would hold even if the actual price of bedaquiline in the UK were higher than in the US.

Analysis of neurocognitive function and CNS endpoints in the PROTEA trial: darunavir/ritonavir with or without nucleoside analogues.

INTRODUCTION: During treatment with protease inhibitor monotherapy, the number of antiretrovirals with therapeutic concentrations in the cerebrospinal fluid (CSF) is lower, compared to standard triple therapy. However, the clinical consequences are unclear. METHODS: A total of 273 patients with HIV RNA <50 copies/mL for over 24 weeks on current antiretrovirals randomized to darunavir/ritonavir (DRV/r) 800/100 mg once-daily, either as monotherapy (n=137) or with 2NRTIs (n=136). Neurocognitive function was evaluated in all patients by the Hopkins Verbal Learning Tests, the Colour Trail Tests and the Grooved Pegboard Test at screening, baseline and at Week 48. A global neurocognitive score (NPZ-5) was derived by averaging the standardized results of the five domains. In a central nervous system (CNS) sub-study (n=70), HIV RNA levels in the CNS were evaluated at baseline and Week 48. Clinical adverse events related to the CNS were collected at each visit. RESULTS: Patients were 83% male and 88% White, with median age 43 years. There were more patients with nadir CD4 count below 200 cells/µL in the DRV/r monotherapy arm (41/137, 30%) than the triple therapy arm (30/136, 22%). At Week 48, there was no difference between the treatment arms for the five combined domains of the neurocognitive score. At Week 48, the percentage of patients with an abnormal neurocognitive score among the five domains was 12.2% for DRV/r monotherapy and 14.9% for triple therapy. However, one patient on DRV/r monotherapy with a CD4 nadir of 17 cells/µL was hospitalized with HIV encephalomyelitis at Week 24, with HIV RNA 2500 copies/mL in the CSF and 125 copies/mL in the plasma. Symptoms resolved after intensification with high dose zidovudine. A second patient on DRV/r monotherapy with CD4 nadir of 166 cells/µL had a rise in HIV RNA in CSF from <40 copies/mL at baseline to 654 copies/mL at Week 48, with concurrent plasma HIV RNA of 77 copies/mL. CONCLUSIONS: In this study for patients with HIV RNA <50 copies/mL at baseline, there was no difference in neurocognitive function between the treatment arms. However two patients on PI monotherapy with CD4 nadir <200 cells/µL developed viraemia in both CSF and plasma, with one symptomatic case. DRV/r monotherapy should be used with caution in patients with nadir CD4 counts below 200 cells/µL.