OBJECTIVE: The primary objective of this study was to estimate survival functions and natural history of patients infected with human immunodeficiency virus (HIV) who were using antiretroviral medication with a protease inhibitor versus those who were under treatment protocols without protease inhibitors. METHOD: Data used in this study were collected using two sources: expert physician surveys and the literature search. The transition were obtained from both sources. The fundamental matrix solution of a Markov chain model was used to estimate survival functions and natural history profiles for HIV-infected patients. The research was conducted from the perspective of a managed care organization. RESULTS: The median survival time of patients with initial CD-4 cell counts above 500/mm3 for the drug regimen without a protease inhibitor was estimated to be 8.6 years compared to 12.9 years for patients taking a combination therapy with one protease inhibitor. Similar results were obtained for patients with various CD4 cell counts at the initiation of therapy. A series of natural history estimates quantified the progress of disease which showed that the use of protease inhibitors significantly reduced the rate of progression of the disease. CONCLUSION: Results from the Markov chain analysis suggested that protease inhibitors significantly improved overall survival of HIV-infected patients by deterring the progression of disease and onset of various opportunistic infections.