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.
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.