title: Should expectations about the rate of new antiretroviral drug development impact the timing of HIV treatment initiation and expectations about treatment benefits?
abstract: BACKGROUND
  Many analyses of HIV treatment decisions assume a fixed formulary of HIV drugs. However, new drugs are approved nearly twice a year, and the rate of availability of new drugs may affect treatment decisions, particularly when to initiate antiretroviral therapy (ART).
  
  
  OBJECTIVE
  To determine the impact of considering the availability of new drugs on the optimal initiation criteria for ART and outcomes in patients with HIV/AIDS.
  
  
  METHODS
  We enhanced a previously described simulation model of the optimal time to initiate ART to incorporate the rate of availability of new antiviral drugs. We assumed that the future rate of availability of new drugs would be similar to the past rate of availability of new drugs, and we estimated the past rate by fitting a statistical model to actual HIV drug approval data from 1982-2010. We then tested whether or not the future availability of new drugs affected the model-predicted optimal time to initiate ART based on clinical outcomes, considering treatment initiation thresholds of 200, 350, and 500 cells/mm3. We also quantified the impact of the future availability of new drugs on life expectancy (LE) and quality-adjusted life expectancy (QALE).
  
  
  RESULTS
  In base case analysis, considering the availability of new drugs raised the optimal starting CD4 threshold for most patients to 500 cells/mm3. The predicted gains in outcomes due to availability of pipeline drugs were generally small (less than 1%), but for young patients with a high viral load could add as much as a 4.9% (1.73 years) increase in LE and a 8% (2.43 QALY) increase in QALE, because these patients were particularly likely to exhaust currently available ART regimens before they died. In sensitivity analysis, increasing the rate of availability of new drugs did not substantially alter the results. Lowering the toxicity of future ART drugs had greater potential to increase benefit for many patient groups, increasing QALE by as much as 10%.
  
  
  CONCLUSIONS
  The future availability of new ART drugs without lower toxicity raises optimal treatment initiation for most patients, and improves clinical outcomes, especially for younger patients with higher viral loads. Reductions in toxicity of future ART drugs could impact optimal treatment initiation and improve clinical outcomes for all HIV patients.
authors: Department of Industrial Engineering, Clemson University, Clemson, South Carolina, United States of America.
authors: Amin
authors: A
authors: Khademi
authors: Department of Medicine, New York University, New York City, New York, United States of America; Division of Comparative Effectiveness and Decision Sciences, Department of Population Health, NYU School of Medicine, New York City, New York, United States of America.
authors: R Scott
authors: RS
authors: Braithwaite
authors: Department of Industrial Engineering, University of Chile, Santiago, RM, Chile.
authors: Denis
authors: D
authors: Saure
authors: Department of Industrial Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors: Andrew J
authors: AJ
authors: Schaefer
authors: Division of Comparative Effectiveness and Decision Sciences, Department of Population Health, NYU School of Medicine, New York City, New York, United States of America.
authors: Kimberly
authors: K
authors: Nucifora
authors: Department of Industrial Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Department of Health Policy and Management, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania, United States of America; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors: Mark S
authors: MS
authors: Roberts
mesh_terms: D000328:Adult; D000367:Age Factors; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D003657:Decision Making; D055808:Drug Discovery / Q000639:trends*; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008017:Life Expectancy; D019057:Quality-Adjusted Life Years; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents