OBJECTIVES: HIV/AIDS incidence and mortality rates have decreased in the U.S. since 1996 due to the use of effective antiretroviral medications and prevention campaigns. The objective of this study is to analyze the trends of prices, utilization, and market shares of antiretroviral medications in the U.S. Medicaid program. METHODS: Antiretroviral drugs include protease inhibitors (PIs), nucleoside analogs (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and fusion inhibitors (FIs). Reimbursement and utilization data from 1991 to 2005 are provided by the Centers for Medicare & Medicaid Services. Descriptive time-series analysis was used to assess quarterly prescription numbers, amount of reimbursement, and spending per prescription. RESULTS: The total reimbursement for antiretroviral drugs in the U.S. Medicaid program increased from $ 30.58 million in 1991 to $1.37 billion in 2005. In 2005, NRTIs as a class had the highest reimbursement market share. These drugs alone accounted for $608.6 million in Medicaid reimbursements (44.4 percent of spending on antiretrovirals). The PIs came in second at $560.4 million (40.9 percent), and the NNRTIs were third at $161.4 million (11.8 percent). The total number of prescriptions increased dramatically from 168,914 in 1991 to 1.99 million in 1998, and 2.73 million in 2005. The number of prescriptions for NRTIs reached 1.38 million in 2005. Prescriptions for PIs increased from 114 in 1995 to 928,949 in 2005. The diffusion of prescriptions for NNRTIs was also rapid from 1,339 prescriptions in 1996 to 401,272 in 2005. Reimbursement per prescription for all drugs, with exception of Agenerase, increased over time. The relatively expensive drugs in 2005 included Trizivir ($1040) and Combivir ($640), as well as Reyataz ($750), Lexiva ($700),Sustiva ($420), Viramune ($370), and Fuzeon ($1914). CONCLUSION: The tremendous growth in antiretroviral spending is due in part to growing utilization of newly developed antiretroviral drugs and in part to rising prices of existing medications.