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 50mg once daily or efavirenz (EFV) 600mg 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 50copies/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 50copies/ml was 79, 78, and 88% for DTG 10, 25, and 50mg, respectively, compared with 72% for EFV. The median increase from baseline in CD4(+) cells was 338cells/l with DTG (all treatment groups combined) compared with 301cells/l 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.