The introduction of highly active antiretroviral therapy has proven highly effective in treating patients with HIV/AIDS. However, the high cost of the advanced antiretroviral therapy has led to increased financial constraints on both patients and payers. From business firms'perspective, especially those with operations in developing countries, it is crucial to determine the long-term economic cost implications of alternative employment and benefit policies for HIV-infected workers or those at high risk for the disease. A simulation model is developed to predict the comprehensive lifetime economic costs of HIV-infected workers to an employer. This model employs age,CD4(+) cell counts,and plasma HIV-1 RNA level as major predictors of the disease progression and patient survival in the determination of various cost functions. Major cost components considered include direct expenses on health insurance premium,life insurance premium, short-term disability benefits, long-term disability benefits, hiring/training expenses, and indirect costs resulting from reduced or lost productivity at work. An individual model and a group model are derived to estimate the costs of an individual and a group of HIV-infected patients, respectively. Over a 10-year period, following the nonadvanced antiretroviral treatment regimen, the group model predicts that the total lifetime cost of an HIV-infected worker can be as high as U.S. 90,000 dollars to his/her employer, of which 60,000 dollars would be various explicit costs and 30,000 dollars lost work productivity. Sensitivity analysis further demonstrated that changes in the initial level of age,CD4(+) cell count, HIV-1 RNA viral load,CD4(+) cell decline rate, and the costs of medical care influence the dynamics of the cost functions. HIV infection can result in sizable economic costs to an employer over the lifetime course of an infected employee if not treated with the advanced antiretroviral therapy. These cost estimates provide a rational economic basis for an employer to optimally assess the longrun costs and benefits of alternative employment and insurance policies in the care of employees with HIV infection.