Influence of alternative thresholds for initiating HIV treatment on quality-adjusted life expectancy: a decision model

Ann Intern Med. 2008 Feb 5;148(3):178-85. doi: 10.7326/0003-4819-148-3-200802050-00004.

Abstract

Background: The optimal threshold for initiating HIV treatment is unclear.

Objective: To compare different thresholds for initiating HIV treatment.

Design: A validated computer simulation was used to weigh important harms from earlier initiation of antiretroviral therapy (toxicity, side effects, and resistance accumulation) against important benefits (decreased HIV-related mortality).

Data sources: Veterans Aging Cohort Study (5742 HIV-infected patients and 11 484 matched uninfected controls) and published reports.

Target population: Individuals with newly diagnosed chronic HIV infection and varying viral loads (10,000, 30,000, 100,000, and 300,000 copies/mL) and ages (30, 40, and 50 years).

Time horizon: Unlimited.

Perspective: Societal.

Intervention: Alternative thresholds for initiating antiretroviral therapy (CD4 counts of 200, 350, and 500 cells/mm3).

Outcome measures: Life-years and quality-adjusted life-years (QALYs).

Results of base-case analysis: Although the simulation was biased against earlier treatment initiation because it used an upper-bound assumption for therapy-related toxicity, earlier treatment increased life expectancy and QALYs at age 30 years regardless of viral load (life expectancies with CD4 initiation thresholds of 500, 350, and 200 cells/mm3 were 18.2 years, 17.6 years, and 17.2 years, respectively, for a viral load of 10,000 copies/mL and 17.3 years, 15.9 years, and 14.5 years, respectively, for a viral load of 300,000 copies/mL), and increased life expectancies at age 40 years if viral loads were greater than 30 000 copies/mL (life expectancies were 12.5 years, 12.0 years, and 11.4 years, respectively, for a viral load of 300,000 copies/mL).

Results of sensitivity analysis: Findings favoring early treatment were generally robust.

Limitations: Results favoring later treatment may not be valid. The findings may not be generalizable to women.

Conclusion: This simulation suggests that earlier initiation of combination antiretroviral therapy is often favored compared with current recommendations.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / adverse effects
  • CD4 Lymphocyte Count
  • Computer Simulation
  • Decision Support Techniques
  • Disease Progression
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • HIV / genetics
  • HIV Infections / drug therapy*
  • HIV Infections / mortality
  • HIV Infections / virology
  • Humans
  • Life Expectancy*
  • Mutation
  • Quality-Adjusted Life Years*
  • Sensitivity and Specificity
  • Time Factors
  • Viral Load

Substances

  • Anti-HIV Agents