OBJECTIVES: To estimate the cost of virologic response at week 48 of treatment with etravirine (ETV), raltegravir (RAL) and maraviroc (MAV) for multi-experienced patients with 2 or more active drugs in the optimized background therapy (OBT) in the Brazilian National AIDS Program. METHODS: Treatment regimens of ETV and RAL were defined by the Brazilian national guidelines. Regimens with MAV were based in the same principles, although the drug is not yet reimbursed. Patients not achieving virologic response followed onto subsequent rescue treatments, defined by the guidelines. Re-treatment was not allowed. Treatment costs included cost of medication as published on the government website. The cost of MAV was defined by law. The number of multi-experienced patients receiving treatment was based on the dispensed capsules of RAL in the last 48 weeks. Virologic response was gathered from the phase III clinical trials of ETV, MAR and RAL, at week 48 for patients with two active drugs in the OBT defined by phenotypic susceptibility. RESULTS: The average cost of treatment at week 48 for multi-experienced patients with at least 2 active drugs in the OBT was R$ 27,243.14 with ETV, compared with R$ 27,702.91 with RAL, and R$ 31,220.72 with MAR.  Given 5,627 multi-experienced patients received treatment, 862 patients failed with MAV, 544 failed treatment with RAL compared to 337 failed patients with ETV. For one third of the cohort (1.875), the total cost of treatment was R$ 58,565,276 for MAV, R$ 51,966,391 for RAL, and R$ 51,103,946 for ETV. CONCLUSIONS: Despite similar treatment costs, treatment with ETV compared to RAL and MAV is a more economic option for the treatment of multi-experienced patients with at least two active drugs in the OBT. At week 48, treatment with RAL and MAV was on average 2% and 15% more expensive compared to ETV, respectively.