OBJECTIVES:   Determine cost-effectiveness and cost-utility of three treatment schemes (based on lopinavir [LPV/r], darunavir [DRV/r] and atazanavir [ATZ/r]) used in patients with HIV/AIDS after a first virological failure, in Colombia. METHODS:   We designed a Markov model with 10 six-month cycles (5-year timeframe) based on efficacy measures obtained from published clinical trials. We estimated local direct costs from a payer perspective using 2009 official rates for drugs and lab tests, and real costs for AIDS-related complications (exchange rate Col$1968 per US$, January 2010). Utilities (in QALYs) were obtained from the Tufts CEA registry. Effectiveness was measured as further virological failures, need of “rescue therapy”, AIDS-related complications, and deaths per 1000 patients (estimated through Monte Carlo probabilistic simulation). We applied a 5% discount rate for costs and QALYs. RESULTS:   Average cost per patient was US$ 39,334 for DRV/r, US$ 41,825 for LPV/r and US$ 49,135 for ATZ/r. Five-year mortality was 5.9% in the DRV/r group, 7.6% for LPV/r and 8.0% for ATZ/r; there were 235 AIDS-related complications in the DRV/r group, 383 in the LPV/r group and 326 in ATZ/r. Rescue therapy was required in 85 occasions in the DRV/r group, 273 in the LPV/r group and 198 in the ATZ/r group, while there were 700 virological failures per 1000 patients in the DRV/r group, 1070 in LPV/r and 1080 in ATZ/r. Average QALYs gained in the five-year period were: DRV/r 3.92; LPV/r 3.81 and ATZ/r 3.84. Cost-utility and cost-effectiveness analysis show darunavir as the dominant alternative since the first year compared to atazanavir, and since the fourth year compared to lopinavir. One way sensitivity analyses did not modify the results significantly. CONCLUSIONS:   In Colombia, initial treatment with darunavir in patients with a first antiretroviral therapy failure is less costly than with lopinavir or atazanavir and is significantly more effective.