OBJECTIVES: To estimate the cost and effects of initiating treatment with atazanavir/r (ATV/r) compared to darunavir/r (DRV/r), lopinavir/r (LPV/r) and efavirenz (EFV) in treatment-naïve HIV-1 patients in Italy(I), Spain(S), Portugal(P) and UK. METHODS: HIV-disease progression is modeled using a micro-simulation model. Health states are a function of HIV-RNA, CD4+cells, AIDS defining events (ADEs), and comorbidities. At model entry patients receive either ATV/r, LPV/r, DRV/r, or EFV with a treatment backbone. Treatment-sequences are modelled following treatment discontinuation due to virological failure, adverse events, resistance, or treatment related co-morbidities. Country-specific patterns for HIV related drug use were applied to estimate specific treatment sequences; maximized at 8 treatment lines after which patient were assumed to be untreated. Efficacy and tolerability inputs of first line treatments were derived from a Mixed-Treatment-Comparison, supplemented by published literature and product-SPCs for remaining drug specific data for efficacy, tolerability and safety. Occurrence of (non)-AIDS defining malignancies was linked to current CD4+cell count and independent of therapy. Cost estimates were based on country specific sources. A 25-year time-horizon was chosen for the base-case analyses. A payer’s perspective was chosen and country-specific discount rates were applied.   RESULTS: Across countries, total costs per patient who started with ATV/r ranged between €126,947(I) and €154,285(P). Predicted incremental costs of ATV/r versus comparators ranged between -€27,004 (S) versus LPV/r and -€13,165 (P) versus EFV. Estimated incremental QALYs of ATV/r versus comparators varied from -0.68(UK) versus EFV to 0.78(UK) versus DRV/r. CONCLUSIONS: The value of initiation with ATV/r in terms of durable viral suppression and favourable side-effect profile was most prominent in Spain. In general, starting with ATV/r is suggested to be a cost-effective treatment strategy for HIV-1 treatment-naïve patients in most of the country-specific comparisons made.