Objective: To develop a simulation model to project costs, life expectancy, and cost-effectiveness in discounted dollars per quality-adjusted life-year (QALY) saved for clinical strategies to prevent Mycobacterium avium complex (MAC) in patients with AIDS.

Methods: We used natural history data from the Multicenter AIDS Cohort Study, efficacy and toxicity data from randomized clinical trials, and cost data from the AIDS Cost and Services Utilization Survey. The model permits timing of prophylaxis to be stratified by CD4 count (201–300, 101–200, 51–100, and ≤ 50/mm3), and allows combinations of prophylaxis, crossover to second- and third-line agents for toxicity, and consideration of adherence, resistance, and quality of life.

Results: The model projects that the average HIV-infected patient with a beginning CD4 count between 201 and 300/mm3 has total lifetime costs of approximately $43,150 and a quality-adjusted life expectancy of 42.35 months. If azithromycin prophylaxis for M. avium complex is begun after the CD4 declines to 50/mm3, costs and quality-adjusted survival increase to approximately $44,040 and 42.78 months, respectively, for an incremental cost-effectiveness ratio of $25,000/QALY compared with no M. avium complex prophylaxis. Other prophylaxis options (i.e., rifabutin, clarithromycin, and combination therapies) either cost more but offer shorter survival, or have cost-effectiveness ratios above $260,000/QALY. Sensitivity analysis reveals that, for reasonable assumptions about quality of life, risk of infection, prophylaxis cost, adherence, and resistance, azithromycin remains the most cost-effective prophylaxis option.

Conclusions: Azithromycin prophylaxis, begun after the CD4 count has declined to 50/mm3, is the most cost-effective M. avium complex prophylaxis strategy. Consistent with new United States Public Health Service guidelines, it should be the first-line prophylaxis option.