title: Potential risks and benefits of HIV treatment simplification: a simulation model of a proposed clinical trial.
abstract: BACKGROUND
  In recent studies, subjects who had achieved suppression of the human immunodeficiency virus (HIV) RNA level while receiving an initial 3-drug antiretroviral regimen successfully maintained suppression while receiving treatment with a "boosted" protease inhibitor (PI) alone. We projected the long-term outcomes of this treatment simplification strategy to inform the design of a proposed multicenter, randomized clinical trial.
  
  
  METHODS
  We used published studies to estimate the efficacy, adverse effects, and cost of a sequence of HIV drug regimens for the simplification strategy, compared with those outcomes for the current standard-of-care (SOC) strategy. Using a published simulation model of HIV disease, we projected life expectancy, discounted quality-adjusted life expectancy (QALE), and discounted lifetime medical costs for each strategy.
  
  
  RESULTS
  Subjects who have not developed PI-resistant HIV infection at the time of failure of the simplification regimen have a greater life expectancy (27.9 vs. 27.1 years) and QALE (14.9 vs. 14.7 years), compared with SOC subjects, because they receive an additional line of therapy without negative consequences for future treatment options. The QALE for the simplification strategy remains higher than that for the SOC, unless a large proportion of patients experiencing virologic failure while receiving the simplification regimen develop PI resistance. Depending on the probability of simplification regimen failure, the advantage is maintained even if HIV develops PI resistance in 42%-70% of subjects. Projected lifetime costs are $26,500-$72,400 per person lower for the simplification strategy than for the SOC strategy.
  
  
  CONCLUSIONS
  An HIV treatment simplification strategy involving use of a boosted PI alone may lead to longer survival overall at lower cost, compared with the SOC combination therapy, because the simplification strategy potentially adds an additional line of therapy. The risk of emergence of PI resistance during treatment with a simplified regimen is a critical determinant of the viability of this strategy.
authors: Department of Public Health, Weill Cornell Medical College, New York, NY 10021, USA. brs2006@med.cornell.edu
authors: Bruce R
authors: BR
authors: Schackman
authors: Callie A
authors: CA
authors: Scott
authors: Paul E
authors: PE
authors: Sax
authors: Elena
authors: E
authors: Losina
authors: Timothy J
authors: TJ
authors: Wilkin
authors: John E
authors: JE
authors: McKinnon
authors: Susan
authors: S
authors: Swindells
authors: Milton C
authors: MC
authors: Weinstein
authors: Kenneth A
authors: KA
authors: Freedberg
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D003198:Computer Simulation; D016527:Drug Costs; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000191:economics / Q000627:therapeutic use*; D006801:Humans; D008017:Life Expectancy; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D019057:Quality-Adjusted Life Years; D018570:Risk Assessment; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors