Background: Compared with 3-drug regimens, two-drug regimens (2DR) have the potential to reduce cumulative drug exposure during life-long antiretroviral therapy in HIV-1 infected patients. In GEMINI-1 and GEMINI-2 (ClinicalTrials.gov: NCT02831673/NCT02831764), the efficacy of the 2DR of DTG+3TC was non-inferior to DTG+ tenofovir/emtricitabine (TDF/FTC) at week 48 in treatment-naïve adults.
Methods: GEMINI-1&2 are identical double-blind, multicentre Phase III studies. Participants with HIV-1 RNA ≤500,000c/mL at screening were randomised 1:1 (stratified by plasma HIV-1 RNA and CD4+ cell count) to once-daily treatment with DTG+3TC or DTG+TDF/FTC. The primary endpoint was the proportion of participants with plasma HIV-1 RNA < 50c/mL at week 48 (Snapshot algorithm). We present efficacy and safety data from prespecified 96-week secondary analyses. 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. At baseline, 20% had HIV-1 RNA >100,000c/mL, 8% had CD4+ < 200cells/mm³. At week 96, DTG+3TC was non-inferior to DTG+TDF/FTC in both GEMINI-1&2 and in the pooled analysis (using a 10% non-inferiority margin) [Table]. Response rates in participants with baseline HIV-1 RNA >100,000c/mL were high and similar between arms. Consistent with week 48 outcomes, response remained lower in DTG+3TC participants with CD4+ < 200cells/mm³. 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. Overall rates of AEs were similar, with low rates of withdrawals due to AEs in both arms. Numerically, 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 96.