OBJECTIVES: Dolutegravir is a new FDA-approved (August 2013) antiretroviral medication in the integrase inhibitor class which could be a possible first-line agent for treatment of antiretroviral naïve HIV infected adults. A phase III trial (SPRING-2) compared clinical efficacy of dolutegravir versus raltegravir, a currently recommended first-line agent, and demonstrated non-inferior viral response rates at 96 weeks for dolutegravir (81%) when compared to raltegravir (76%). This study aims to estimate the costs and effectiveness of dolutegravir and raltegravir and to determine the cost-effectiveness of dolutegravir versus raltegravir. METHODS: A decision analysis model was constructed to determine the cost-effectiveness of treatment with dolutegravir versus treatment with raltegravir as a first-line agent from the perspective of the provider. First-line efficacy data was derived from the previously-mentioned published phase-III trial (SPRING-2).  Drug costs were estimated using average whole sale price and data were obtained using the Red Book. Costs associated with second-line treatment as well as adverse effect treatment were also derived from the Red Book. The model was run over a period of 192 weeks using TreeAge Pro 2013. RESULTS: The estimated costs for the dolutegravir arm and raltegravir arm at 192 weeks were $100,750.28 and $96,622.17, respectively. The incremental cost-effectiveness ratio for dolutegravir versus raltegravir was estimated to be $412,811 per 1% increase in virological success. Sensitivity analysis performed on the cost parameters confirmed the primary cost effectiveness results. CONCLUSIONS: The analysis provided cost-effectiveness findings of dolutegravir versus raltegravir for HIV-infected treatment naïve patients and showed favorable cost-effectiveness results for raltegravir when using a 192 week time frame.