Background: The requirement for life-long antiretroviral therapy of HIV infection has highlighted interest in 2-drug regimens (2DRs) to minimise cumulative drug exposure. DTG´s potency, safety and resistance barrier make it an optimal core agent for 2DRs while 3TC´s safety, tolerability and efficacy make it an attractive partner for initial HIV-1 treatment.
Methods: GEMINI-1 and GEMINI-2 are two identical global double-blind, multicentre Phase III studies evaluating efficacy and safety of DTG+3TC once daily in treatment-naïve HIV-1-infected adults with Screening HIV-1 RNA ≤500,000c/mL (ClinicalTrials.gov: NCT02831673/NCT02831764). Participants were randomised 1:1 (stratified by Screening plasma HIV-1 RNA and CD4+ cell count) to treatment with DTG+3TC or DTG+TDF/FTC. The primary endpoint is the proportion of participants with plasma HIV-1 RNA < 50c/mL at Week 48 (Snapshot algorithm).
Results: 714 and 719 adults were randomised and treated in GEMINI-1&2, respectively. Participants were well matched for demographic/baseline characteristics. Overall, 20% of participants had baseline HIV-1 RNA >100,000c/mL; median CD4+ was 432 cells/mm³. Based on a 10% non-inferiority margin, DTG+3TC was non-inferior to DTG+TDF/FTC at Week 48 in both GEMINI-1&2 and in the pooled analysis [Table]. Response rates in subjects with baseline HIV-1 RNA >100,000 c/mL were high and similar between arms. Across both studies, 6 participants on DTG+3TC and 4 on DTG+TDF/FTC met protocol-defined virologic withdrawal criteria through Week 48; none had treatment-emergent primary integrase-strand transfer inhibitor or NRTI resistance mutations. Overall rates of AEs were similar between arms, with low rates of withdrawals due to AEs for both DTG+3TC and DTG+TDF/FTC. More drug related AEs were reported with DTG+TDF/FTC. Post baseline changes in markers of bone and renal function favoured DTG+3TC through week 24.