title: Genotype assays and third-line ART in resource-limited settings:  a simulation and cost-effectiveness analysis of a planned clinical trial.
abstract: OBJECTIVE
  To project the clinical and economic outcomes of a genotype assay for selection of third-line antiretroviral therapy (ART) in resource-limited settings, as per the planned international A5288 trial (MULTI-OCTAVE).
  
  
  METHODS
  We used the Cost-effectiveness of Preventing AIDS Complications (CEPAC)-International Model to compare three strategies for patients who have failed second-line ART in South Africa: sustained second-line: no genotype assay, all patients remain on second-line ART; A5288: genotype to determine the resistance profile and assign an appropriate regimen; or population-based third-line: no genotype, all patients switch to a potent third-line regimen. Model inputs are from published data in South Africa. Resistance profiles, ART regimens, and efficacy data were those used for trial planning.
  
  
  RESULTS
  Projected life expectancy for sustained second-line, A5288, and population-based third-line are 61.1, 103.8, and 104.2 months. Compared to sustained second-line ($12 ,460), per person lifetime costs increase for the A5288 ($39, 250) and population-based ($44, 120) strategies. The incremental cost-effectiveness ratio of A5288, compared to sustained second-line, is $7500/year of life saved (YLS), and for population-based third-line, compared to A5288, is $154 ,500/YLS. In the A5288 strategy, very late presentation to care, coupled with lengthy delays to obtain the genotype, dramatically reduces 5-year survival, making the population-based third-line strategy more attractive.
  
  
  CONCLUSIONS
  We project that, whereas the public health approach to third-line therapy is unaffordable, genotype assays and third-line ART in resource-limited settings will increase survival and be cost-effective compared to the population-based approach, supporting the value of an efficacy study.
authors.affiliation: Division of Infectious Disease, Department of Medicine, Massachusetts General Hospital, and Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Lorenzana
authors.forename: Michael D
authors.initials: MD
authors.lastname: Hughes
authors.forename: Beatriz
authors.initials: B
authors.lastname: Grinsztejn
authors.forename: Ann C
authors.initials: AC
authors.lastname: Collier
authors.forename: Paula Mendes
authors.initials: PM
authors.lastname: Luz
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Freedberg
authors.forename: Robin
authors.initials: R
authors.lastname: Wood
authors.forename: Julie H
authors.initials: JH
authors.lastname: Levison
authors.forename: Peter N
authors.initials: PN
authors.lastname: Mugyenyi
authors.forename: Robert
authors.initials: R
authors.lastname: Salata
authors.forename: Carole L
authors.initials: CL
authors.lastname: Wallis
authors.forename: Milton C
authors.initials: MC
authors.lastname: Weinstein
authors.forename: Robert T
authors.initials: RT
authors.lastname: Schooley
authors.forename: Rochelle P
authors.initials: RP
authors.lastname: Walensky
mesh_terms: D019380:Anti-HIV Agents / Q000191:economics* / Q000627:therapeutic use; D002986:Clinical Trials as Topic / Q000191:economics*; D003362:Cost-Benefit Analysis; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000191:economics*; D006801:Humans; D008017:Life Expectancy; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D013019:South Africa; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents