title: HIV preexposure prophylaxis in the United States: impact on lifetime infection risk, clinical outcomes, and cost-effectiveness.
abstract: BACKGROUND
  The combination of tenofovir and emtricitabine shows promise as HIV preexposure prophylaxis (PrEP). We sought to forecast clinical, epidemiologic, and economic outcomes of PrEP, taking into account uncertainties regarding efficacy, the risks of developing drug resistance and toxicity, behavioral disinhibition, and drug costs.
  
  
  METHODS
  We adapted a computer simulation of HIV acquisition, detection, and care to model PrEP among men who have sex with men and are at high risk of HIV infection (i.e., 1.6% mean annual incidence of HIV infection) in the United States. Base-case assumptions included 50% PrEP efficacy and monthly tenofovir-emtricitabine costs of $753. We used sensitivity analyses to examine the stability of results and to identify critical input parameters.
  
  
  RESULTS
  In a cohort with a mean age of 34 years, PrEP reduced lifetime HIV infection risk from 44% to 25% and increased mean life expectancy from 39.9 to 40.7 years (21.7 to 22.2 discounted quality-adjusted life-years). Discounted mean lifetime treatment costs increased from $81,100 to $232,700 per person, indicating an incremental cost-effectiveness ratio of $298,000 per quality-adjusted life-year gained. Markedly larger reductions in lifetime infection risk (from 44% to 6%) were observed with the assumption of greater (90%) PrEP efficacy. More-favorable incremental cost-effectiveness ratios were obtained by targeting younger populations with a higher incidence of infection and by improvements in the efficacy and cost of PrEP.
  
  
  CONCLUSIONS
  PrEP could substantially reduce the incidence of HIV transmission in populations at high risk of HIV infection in the United States. Although it is unlikely to confer sufficient benefits to justify the current costs of tenofovir-emtricitabine, price reductions and/or increases in efficacy could make PrEP a cost-effective option in younger populations or populations at higher risk of infection. Given recent disappointments in HIV infection prevention and vaccine development, additional study of PrEP-based HIV prevention is warranted.
authors.affiliation: Department of Epidemiology and Public Health, Yale School of Medicine, New Haven, Connecticut 06520-8034, USA. david.paltiel@yale.edu
authors.forename: A David
authors.initials: AD
authors.lastname: Paltiel
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Freedberg
authors.forename: Callie A
authors.initials: CA
authors.lastname: Scott
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Schackman
authors.forename: Elena
authors.initials: E
authors.lastname: Losina
authors.forename: Bingxia
authors.initials: B
authors.lastname: Wang
authors.forename: George R
authors.initials: GR
authors.lastname: Seage
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Sloan
authors.forename: Paul E
authors.initials: PE
authors.lastname: Sax
authors.forename: Rochelle P
authors.initials: RP
authors.lastname: Walensky
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000191:economics / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000191:economics* / Q000627:therapeutic use*; D018890:Chemoprevention / Q000379:methods*; D003198:Computer Simulation; D003362:Cost-Benefit Analysis; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000191:economics / Q000627:therapeutic use; D000068679:Emtricitabine; D015658:HIV Infections / Q000517:prevention & control*; D006716:Homosexuality; D006801:Humans; D008297:Male; D063065:Organophosphonates / Q000191:economics / Q000627:therapeutic use; D018570:Risk Assessment; D000068698:Tenofovir; D014481:United States
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine