Introduction: GESIDA (AIDS Study Group) and the National AIDS Plan panel of experts propose "preferred regimens" of antiretroviral treatment (ART) as initial therapy in HIV infected patients. These preferred regimens are based on the results of clinical trials, and on the opinions of the experts of the panel. The objective of this study is to evaluate the costs and the cost effectiveness of initiating treatment following these guidelines. Methods: Economic assessment of costs and cost effectiveness through the construction of decision trees. Effectiveness was defined as the probability of having viral load <50 copies/mL at week 48 in an intention-to-treat analysis. The perspective of the analysis is that of the National Health System, taking into account only the differential direct costs (ART, management of adverse effects, studies of resistance, and determination of HLA B* 5701). The area is Spain, the time horizon is 48 weeks, and the costs are those of 2011. A deterministic sensitivity analysis was performed, building three scenarios for each regimen: baseline, the most favourable, and the most unfavourable. Results: In the baseline scenario, the cost of initiating treatment ranges from 7,550 Euros for the ABC/3TC + EFV to 13,327 Euros for TDF/FTC + RAL. The efficacy ranges between 0.66 for ABC/3TC + LPV/r and 0.86 for TDF/FTC + RAL. Efficiency, in terms of cost effectiveness, varies between 10,175 and 15,539 Euros per responder at 48 weeks, for TDF/FTC/EFV and TDF/FTC + RAL respectively. Conclusion: The most efficient regimen was TDF/FTC + EFV, followed by ABC/3TC + EFV. Sensitivity analysis confirms the robustness of these findings. © 2011 Elsevier Espãna, S.L. All rights reserved.