C1. Clinical trials (abstracts submitted to C1 should choose a secondary category that describes the subject matter of the trial)
Oral Abstract Submission
Background : At Weeks 48 and 96 in the GEMINI-1 & GEMINI-2 studies (Clinicaltrials.gov: NCT02831673 & NCT02831764), the 2DR of DTG+3TC was non-inferior to the three-drug regimen of DTG + tenofovir/emtricitabine (TDF/FTC) in achieving plasma HIV-1 RNA < 50 c/mL in treatment-naïve adults.
Methods : GEMINI-1&2 are identical, global, double-blind, multicenter Phase III studies. Participants with screening HIV-1 RNA ≤ 500,00 c/mL were randomised to once daily DTG+3TC or DTG+TDF/FTC, stratified by plasma HIV-1 RNA and CD4+ cell count. The primary endpoint was the proportion of participants with plasma HIV-1 RNA < 50 c/mL at Week 48 (Snapshot algorithm). We present a secondary endpoint analysis of efficacy at Week 96 by baseline disease and demographic characteristics. For the overall population, estimates and confidence intervals were based on a stratified analysis using Cochran-Mantel-Haenszel weights.
Results : 714 and 719 adults were randomised and treated in GEMINI-1&2, respectively. Based on a 10% non-inferiority margin, DTG+3TC was non-inferior to DTG+TDF/FTC at Week 96 in both GEMINI-1&2 and in the pooled analysis. Response rates across baseline HIV-1 RNA subgroups were high and similar in both arms in the pooled analysis, including in participants with baseline HIV-1 RNA > 100,000 c/mL [Table 1]. Results were also generally consistent regardless of age, gender, or race. In the CD4+ ≤ 200 cells/mm3 subgroup, response rates were lower in the DTG+3TC group compared to DTG+TDF/FTC; most reasons for non-response were unrelated to virologic efficacy or treatment regimen. Across both studies, 11 participants on DTG+3TC and 7 on DTG+TDF/FTC met protocol-defined virologic withdrawal criteria through Week 96; none had treatment emergent integrase-strand-transfer-inhibitor or NRTI resistance mutations.
Conclusion : In GEMINI-1&2, DTG+3TC was non-inferior to DTG+TDF/FTC in treatment-naïve adults at Week 96, demonstrating durable efficacy. The results of subgroup analyses of efficacy at Week 96 were generally consistent with overall study results, and further demonstrate that DTG+3TC is an effective initial treatment for HIV-infected patients across a spectrum of disease characteristics and patient populations. The studies are ongoing.