Dolutegravir in antiretroviral-naive adults with HIV-1: 96-week results from a randomized dose-ranging study

OBJECTIVE To evaluate the efficacy and safety/tolerability of dolutegravir (DTG, S/GSK1349572), a potent inhibitor of HIV integrase, through the full 96 weeks of the SPRING-1 study. DESIGN ING112276 (SPRING-1) was a 96-week, randomized, partially blinded, phase IIb dose-ranging study. METHODS Treatment-naive adults with HIV received DTG 10, 25, or 50 mg once daily or efavirenz (EFV) 600 mg once daily (control arm) combined with investigator-selected dual nucleos(t)ide reverse transcriptase inhibitor backbone regimen (tenofovir/emtricitabine or abacavir/lamivudine). The primary endpoint of the study was the proportion of participants with plasma HIV-1 RNA less than 50 copies/ml, based on time to loss of virologic response at 16 weeks (conducted for the purpose of phase III dose selection), with a planned analysis at 96 weeks. Safety and tolerability were also assessed. RESULTS Of 208 participants randomized to treatment, 205 received study drug. At week 96, the proportion of participants achieving plasma HIV-1 RNA less than 50 copies/ml was 79, 78, and 88% for DTG 10, 25, and 50 mg, respectively, compared with 72% for EFV. The median increase from baseline in CD4 cells was 338 cells/μl with DTG (all treatment groups combined) compared with 301 cells/μl with EFV (P  = 0.155). No clinically significant dose-related trends in adverse events were observed, and fewer participants who received DTG withdrew because of adverse events (3%) compared with EFV (10%). CONCLUSION Throughout the 96 weeks of the SPRING-1 study, DTG demonstrated sustained efficacy and favorable safety/tolerability in treatment-naive individuals with HIV-1.