OBJECTIVES: To conduct pharmacoeconomic analysis of ritonavir-boosted atazanavir (ATV/r) vs ritonavir-boosted lopinavir (LPV/r) and ritonavir-boosted darunavir (DRV/r) in combination with nucleoside reverse transcriptase inhibitors (NRTIs) in treatment-naïve adult patients with HIV-infection from Russian healthcare system point of view. METHODS: Cost-effectiveness analysis (CEA) with calculation of incremental cost-effectiveness ratio (ICER) was used for comparison of ATV/r with LPV/r. Cost-minimization analysis (CMA) with calculation of cost minimization difference (CMD) was used for comparison of ATV/r with DRV/r. Direct comparison of clinical efficacy and safety of ATV/r vs LPV/r was based on the results of randomized controlled trial (RCT) CASTLE. Indirect comparison of clinical efficacy and safety of ATV/r with DRV/r was performed on the basis of results of RCTs CASTLE and ARTEMIS. Virological response after 96 weeks of treatment and protease inhibitors (PIs)-induced diarrhea were considered as clinical efficacy and safety outcomes, respectively. Direct medical costs were calculated for the hypothetical cohort of 100 patients treated for 96 weeks. RESULTS: ATV/r + NRTIs had statistically significant higher rate of virological response after 96 weeks of treatment than LPV/r + NRTIs (risk ratio (RR) = 1.090 [95% CI 1.002; 1.186], p<0.05) with statistically significant lower risk of PI-induced diarrhea (RR = 0.202 [95% CI 0.107; 0.381], p<0.0001). There were no statistically significant difference between combinations ATV/r + NRTIs and DRV/r + NRTIs in terms of rate of virological response and risk of PI-induced diarrhea (RR = 0.981 [95% CI 0.869; 1.107], p=0.77 and 0.543 [95% CI 0.227; 1.296], p=0.17, respectively). ICER for ATV/r vs LPV/r was 4063.58 EUR per one additional patient with virological response. CMD for ATV/r vs DRV/r was 5485.38 EUR per patient. CONCLUSIONS: ATV/r is more preferable than LPV/r and DRV/r for administration in combination with NRTIs in treatment-naïve adult patients with HIV infection.