SPRING-2 is a phase III, non-inferiority, double-blind randomized trial of 96 weeks duration. Naïve HIV-1 infected adults received either dolutegravir 50 mg once daily (n = 411) or raltegravir 400 mg twice daily (n = 411), both in combination with either tenofovir/emtricitabine or abacavir/lamivudine. By intention to treat using the snapshot algorithm, the proportion of patients with HIV-1 RNA < 50 copies/ml at week 96 was 81% in the dolutegravir group, compared with 76% in the raltegravir group (difference 4.5%, 95% CI -1.1% to 10.0%), confirming week 48 primary endpoint that dolutegravir was non-inferior to raltegravir. Overall, few patients (10 in each group, 2%) discontinued for adverse events. Rate and nature of adverse events, mostly of grade 1 were similar in both groups. Resistance emergence to integrase in protocol-defined virologic failures (2 consecutive plasma HIV-1 RNA > 50 c/ml at or after week 24) was seen in no patients in the dolutegravir group and 1 in the raltegravir group. Mean decrease in estimated creatinine clearance through 96 weeks was higher in the dolutegravir group (- 19.6 vs -9.3 ml/min).