Once-daily dolutegravir (DTG; S/GSK1349572) is non-inferior to raltegravir (RAL) in antiretroviral‑naive adults: 48 week results from SPRING-2 (ING113086)
Background: The integrase inhibitor, Dolutegravir (DTG; S/GSK1349572), has shown rapid and durable antiviral response, with a favorable tolerability profile.
Methods: In this multicenter, double-dummy-blinded, Phase III, non-inferiority study, HIV-1 infected ART-naive adults with HIV-1 RNA ≥1000 c/mL and no evidence of viral resistance were randomized 1:1 to receive DTG 50 mg QD or RAL 400 mg BID, in addition to investigator-selected backbone NRTIs of either TDF/FTC or ABC/3TC. Subjects were stratified by screening HIV-1 RNA (≤ and >100,000 c/mL) and backbone NRTI selection. The primary endpoint was proportion of subjects with HIV-1 RNA < 50 c/mL through Week 48 (FDA “snapshot” algorithm).
Results: 827 subjects were randomized (DTG n=413, RAL n=414). At baseline: median age 36 years, 14% female, 15% non-white, 28% HIV-1 RNA >100,000 c/mL, 41% ABC/3TC. Proportion of subjects meeting the primary endpoint was 88% for DTG and 85% for RAL; difference (2.5%; 95% CI: -2.2% to 7.1%) met 10% non-inferiority criteria. For subjects with HIV-1 RNA >100,000 c/mL, response rate was 82% for DTG vs 75% for RAL. Secondary analyses supported non-inferiority: HIV-1 RNA < 50 c/mL per-protocol (DTG 90% vs RAL 88%), treatment-related discontinuation=failure (93% vs 92%) and virologic non-response (5% vs 8%). Median CD4 increases were similar (230 cells/mm3 each). Most commonly reported (≥10%) adverse events (AEs) were nausea (DTG 14%, RAL 13%), headache (12% each), nasopharyngitis (11%, 12%) and diarrhea (11% each). Discontinuation due to AEs was 2% in each group. At virologic failure, there was no genotypic integrase or NRTI resistance in the DTG group vs 1 subject and 4 subjects, respectively, in the RAL group.
Conclusions: At week 48, once-daily DTG was non-inferior to twice-daily RAL in treatment-naive HIV-1 infected subjects, with no evidence of emergent resistance to DTG in virologic failure. DTG plus NRTIs could be an option for first-line HIV treatment.
19th International AIDS Conference
"F.Raffi, et al.
Once-daily dolutegravir (DTG; S/GSK1349572) is non-inferior to raltegravir (RAL) in antiretroviral‑naive adults: 48 week results from SPRING-2 (ING113086).
19th International AIDS Conference: