Introduction: GESIDA and the AIDS National Plan panel of experts suggest preferred (PR), alternative (AR) and other regimens (OR) for antiretroviral treatment (ART) as initial therapy in HIV-infected patients for 2016. The objective of this study is to evaluate the costs and the efficiency of initiating treatment with these regimens. Methods: Economic assessment of costs and efficiency (cost/efficacy) based on decision tree analyses. Efficacy 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 considering only 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 2016. A sensitivity deterministic 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 4,663 Euros for 3TC + LPV/r (OR) to 10,894 Euros for TDF/FTC + RAL (PR). The efficacy 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/efficacy, ranges from 5,280 to 12,836 Euros per responder at 48 weeks, for 3TC + LPV/r (OR) and RAL + DRV/r (OR) respectively. Conclusion: Despite the overall most efficient regimen was 3TC + LPV/r (OR), among the PR and AR, the most efficient regimen was ABC/3TC/ DTG (PR). Among the AR regimes, the most efficient was TDF/FTC/RPV.