title: Cost effectiveness of darunavir/ritonavir 600/100 mg bid in treatment-experienced, lopinavir-naive, protease inhibitor-resistant, HIV-infected adults in Belgium, Italy, Sweden and the UK.
abstract: BACKGROUND
  Using data from the phase IIb POWER trials, darunavir boosted with low-dose ritonavir (DRV/r; 600/100 mg twice daily; bid)-based highly active antiretroviral therapy (HAART) was shown to be significantly more efficacious and cost effective than other protease inhibitor (PI)-based therapy in highly treatment-experienced, HIV-1-infected adults. Furthermore, in the phase III TITAN trial (TMC114-C214), DRV/r 600/100 mg bid-based HAART generated a superior 48-week virological response rate compared with standard-of-care lopinavir/ritonavir (LPV/r; 400/100 mg bid)-based therapy in treatment-experienced, lopinavir-naive patients, and in particular those with one or more International AIDS Society - USA (IAS-USA) primary PI resistance-associated mutations at baseline. These patients had a broader degree of previous PI use/failure (0 - ≥ 2) than the POWER patients.
  
  
  OBJECTIVE
  To determine whether DRV/r 600/100 mg bid-based HAART is cost effective compared with LPV/r-based therapy, from the perspective of Belgian, Italian, Swedish and UK reimbursement authorities, when used in treatment-experienced patients similar to TITAN patients with one or more IAS-USA primary PI mutations at baseline.
  
  
  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/mm³) and an absorbing state of death was adapted for use in the above-mentioned healthcare settings. Baseline demographics, CD4 cell count distribution, antiretroviral drug usage, virological/immunological response rates and matching transition probabilities were based on data collected during the first 48 weeks of therapy in the modelled subgroup of TITAN patients and the published literature. After treatment failure, patients were assumed to switch to a follow-on combination regimen. For each health state, utility values and mortality rates were obtained from the published literature. Data from local observational studies (Belgium, Sweden and Italy) or the published literature (UK) 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 chosen based on local guidelines.
  
  
  RESULTS
  The base-case analysis predicted quality-adjusted life year (QALY) gains of 0.785 in Belgium, 0.608 in Italy, 0.584 in Sweden and 0.550 in the UK when DRV/r-based therapy was used instead of LPV/r-based treatment. The estimated base-case incremental cost-effectiveness ratios (ICERs) were €6964/QALY gained in Belgium, €9277/QALY gained in Italy, €6868 (SEK69,687)/QALY gained in Sweden and €14,778 (£12 612)/QALY gained in the UK. Assuming a threshold of €30,000/QALY gained, DRV/r-based therapy remained cost effective over most parameter ranges tested in extensive one-way sensitivity analyses. The variation of immunological response rates and the time horizon were identified as important drivers of cost effectiveness. Probabilistic sensitivity analysis revealed a greater than 70% probability of achieving an ICER below this threshold in all four healthcare settings.
  
  
  CONCLUSIONS
  From the perspective of Belgian, Italian, Swedish and UK payers, DRV/r 600/100 mg bid-based HAART is predicted to be cost effective compared with LPV/r 400/100 mg bid-based therapy, when used to manage treatment experienced, lopinavir-naive, PI-resistant, HIV-infected adults with a broad range of previous PI use/failure.
authors.affiliation: IMS Health, Health Economics Outcomes Research, Brussels, Belgium. KMoeremans@be.imshealth.com
authors.forename: Karen
authors.initials: K
authors.lastname: Moeremans
authors.forename: Lindsay
authors.initials: L
authors.lastname: Hemmett
authors.forename: Jonas
authors.initials: J
authors.lastname: Hjelmgren
authors.forename: Gabriele
authors.initials: G
authors.lastname: Allegri
authors.forename: Erik
authors.initials: E
authors.lastname: Smets
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000191:economics; D001530:Belgium; D018791:CD4 Lymphocyte Count / Q000191:economics; D017322:Clinical Trials, Phase II as Topic; D003362:Cost-Benefit Analysis; D000069454:Darunavir; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000191:economics* / Q000401:mortality / Q000821:virology; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000191:economics* / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects; D017048:Health Care Costs; D006801:Humans; D007558:Italy; D061466:Lopinavir; D008297:Male; D008390:Markov Chains; D015337:Multicenter Studies as Topic; D011744:Pyrimidinones / Q000009:adverse effects / Q000191:economics* / Q000627:therapeutic use; D019057:Quality-Adjusted Life Years; D012367:RNA, Viral / Q000097:blood; D016032:Randomized Controlled Trials as Topic; D019438:Ritonavir / Q000009:adverse effects / Q000191:economics* / Q000627:therapeutic use; D013449:Sulfonamides / Q000191:economics* / Q000627:therapeutic use; D013548:Sweden; D006113:United Kingdom; D019562:Viral Load / Q000191:economics
chemical_list: D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D012367:RNA, Viral; D013449:Sulfonamides; D061466:Lopinavir; D019438:Ritonavir; D000069454:Darunavir