OBJECTIVES: To analyze the changes in the antiretroviral pharmacotherapy during 2006-2010 and its impact on cost and disease control of HIV/AIDS patients in Bulgaria. METHODS: Micro costing approach was used based on retrospective analysis of patients’ records in major clinic for immunosuppressed patients at the University hospital of infectious and parasitic diseases in Sofia. Information was gathered for the way of diseases transmission, antiretroviral combinations and their cost, CD4 count and viral load per patient per year. It was evaluated the changes in the dosage regimes, cost of therapy and its influence on CD4 count and viral load. RESULTS: On total 162 patients were included in the study. Nearly 40 different dosage regimes were identified and all of them are combinations of 3 or 4 medicines. During the period were introduces 3 new antiretroviral medicines (tenofovir, emtricitabin, darunavir). The average yearly cost of pharmacotherapy (all regimes and patients) is increasing from 155 837.64 euro to 319 571.76 euro during 2006 - 2010 due to switch of the therapy for some of the patients to newer medicines because of drug toxicity, resistance or other reasons. All newly registered patients are treated with the new antiretroviral products and their yearly cost of therapy is 178251.12 euro. Introduction of the new medicines led to the increase in total pharmacotherapy cost with 291 89.64 euro, but also to better control measured with the increase in CD4 count (>500) and sustained suppression of vial load to <20 in 45.46% of patients. CONCLUSIONS: HIV/AIDS remain costly diseases for the Bulgarian population but new medicines led to better control on its progress and thus could save further hospital cost.