OBJECTIVES: In the last years in Mexico HIV/AIDS appears within the first seven causes of mortality among the population between 15 and 64 years old (SINAIS). Boosted PI combination therapy, in combination with other advances, has lowered the mortality rate among HIV-infected patients almost to that of the uninfected population. The 96-week CASTLE randomized trial demonstrated that, in HAART-naïve patients, ATV/RTV was non-inferior to LPV/RTV for suppressing viral replication and caused lower rates of GI toxicity and lower increases in total cholesterol. In this study we evaluated the cost-effectiveness of ATV/RTV versus LPV/RTV in treatment-naïve HIV patients in Mexico, using results from the CASTLE study. METHODS: A lifetime Markov micro simulation model was used to estimate the cost per QALY for both therapies lifetime costs, clinical outcomes and cost-effectiveness. Tenofovir-emtricitabine was considered the backbone therapy. A million-member cohort of HIV-infected, treatment-naïve adults progressed at 3-month intervals through 8 health states. The model measures the cost per adverse event averted of the ATV based regime, focusing in particular on GI and coronary heart disease outcomes.  The analysis was conducted from the Mexican Health care perspective. Outcomes were discounted at a 5% rate. Virologic suppression, health state transition probabilities, cholesterol changes, and side effect rates were derived from CASTLE. Costs and utilities were derived from literature and expert opinion. RESULTS: Patients initiating ATV+RTV regime had longer quality-adjusted survival than those initiating LPV+RTV, (10.47 vs. 10.26 years) and lower total costs ($95,579 vs. $103,891 USD) resulting in a more effective and less costly treatment option (dominant alternative). Sensitivity analyses demonstrated that the model is robust to a wide range of parameter estimates. CONCLUSIONS: This analysis suggests that the use of ATV+RTV in the Mexican healthcare setting is a preferred option when compared to LPV+RTV for treatment of treatment-naïve HIV patients.