© 2015 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. Introduction GESIDA and the AIDS National Plan panel of experts suggest a preferred (PR), alternative (AR) and other regimens (OR) for antiretroviral treatment (ART) as initial therapy in HIV-infected patients for 2015. The objective of this study is to evaluate the costs and the effectiveness of initiating treatment with these regimens. Methods Economic assessment of costs and effectiveness (cost/effectiveness) based on decision tree analyses. Effectiveness was defined as the probability of reporting a viral load <50 copies/mL at week 48, in an intention-to-treat analysis. Cost of initiating treatment with an ART regimen was defined as the costs of ART and its consequences (adverse effects, changes of ART regimen, and drug resistance studies) during the first 48 weeks. The payer perspective (National Health System) was applied, only taking into account differential direct costs: ART (official prices), management of adverse effects, studies of resistance, and HLA B∗5701 testing. The setting is Spain and the costs correspond to those of 2015. A deterministic sensitivity analysis was conducted, building three scenarios for each regimen: base case, most favourable and least favourable. Results In the base case scenario, the cost of initiating treatment ranges from 4663 Euros for 3TC + LPV/r (OR) to 10,902 Euros for TDF/FTC + RAL (PR). The effectiveness varies from 0.66 for ABC/3TC + ATV/r (AR) and ABC/3TC + LPV/r (OR), to 0.89 for TDF/FTC + DTG (PR) and TDF/FTC/EVG/COBI (AR). The efficiency, in terms of cost/effectiveness, ranges from 5280 to 12,836 Euros per responder at 48 weeks, for 3TC + LPV/r (OR) and RAL + DRV/r (OR), respectively. Conclusion The most efficient regimen was 3TC + LPV/r (OR). Among the PR and AR, the most efficient regimen was TDF/FTC/RPV (AR). Among the PR regimes, the most efficient was ABC/3TC + DTG.