OBJECTIVES: To analyze the changes in the highly active antiretroviral pharmacotherapy during the period 2006-2011 and its impact on cost and disease control of HIV/AIDS patients in Bulgaria. METHODS: It is a combined retrospective and prospective observational real life study on cost and therapeutic results of AIDS patient’s therapy. Information was gathered for 2/3 of the treated patients for the antiretroviral combinations therapy and its cost, CD4 count and viral load. The changes in the dosage regimes, cost of therapy and its influence on CD4 count and viral load were evaluated. Descriptive statistic, Willcoxon tests, and Spearman correlation analysis were applied. RESULTS: On total 162 patients were included and out of them 48 identified with the changes in their therapy. Nearly 40 different dosage regimes were found prescribed as combinations of 3 or 4 medicines. During the period were introduces 3 new antiretroviral medicines (tenofovir, emtricitabine, darunavir). The average yearly cost of pharmacotherapy is increasing from 155 837.64 euro to 319 571.76 euro during 2006 - 2011. To all treatment naive patients were prescribed the newly authorized medicines that lead to sustained suppression of viral load to <20 in 45.46%. Introduction of the new medicines led to the increase in total pharmacotherapy cost with 291 89.64 euro, but also to better disease control. Statistically significant were the changes in the mean cost of therapy in 2007 vs 2006 (p=0,0002) and in 2010 vs 2009 (p<0,0001). We found the statistically significant changes among the mean cost of therapy and viral load (p=0,0221), as well as among the mean cost of therapy and CD4 count (p=0,05). The correlation among the therapeutic results and the therapeutic combinations were found in 2011 (p=0,0064).  CONCLUSIONS: AIDS remain costly disease for the health insurance budget but new medicines led to better control on its progression.