Glasgow 2018—2-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) is non–inferior to dolutegravir plus  tenofovir/emtricitabine (DTG + TDF/FTC) at 48 weeks in antiretroviral treatment-naïve adults with HIV-1 infection: subgroup analyses in the GEMINI studies1

Background: Two-drug regimens (2DR) are being evaluated against standard 3-drug regimens for their potential to reduce cumulative drug exposure and drug-drug interactions during life-long antiretroviral therapy in patients with HIV-1 infection. In the GEMINI studies, the efficacy of the 2DR of DTG+3TC was recently shown to be non-inferior to DTG+TDF/FTC at 48-weeks in treatment-naïve adults.

Methods and Materials: GEMINI-1&2 are 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 to treatment with DTG+3TC or DTG+TDF/FTC, stratified by Screening plasma HIV-1 RNA and CD4+ cell count. The primary endpoint was the proportion of participants with plasma HIV-1 RNA <50c/mL at Week 48 (Snapshot algorithm). We present a secondary analysis of the primary endpoint and of safety by demographic and baseline plasma HIV-1 RNA and CD4+ cell count subgroups. For the primary endpoint, estimates and confidence intervals were based on a stratified analysis using Cochran-Mantel-Haenszel weights. The subgroup analysis was unadjusted.

Results: 714 and 719 adults were randomised and treated in GEMINI-1&2, respectively. Participants were well matched for demographic and baseline characteristics. Based on a 10% non-inferiority margin, DTG+3TC was non-inferior to DTG+TDF/FTC at Week 48 in both GEMINI-1&2. Results were generally consistent regardless of age, gender, race or baseline HIV-1 RNA [Table 1]. Response rates in subjects with baseline HIV-1 RNA >100,000c/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 integrase-strand- transfer-inhibitor or NRTI resistance mutations. Overall rates of AEs were similar between arms, with low rates of withdrawals due to AEs in both arms [GEMINI-1&2 pooled: DTG+3TC 15/716 (2%) vs. DTG+TDF/FTC 16/717 (2%)]. More drug related AEs were reported with DTG+TDF/FTC [GEMINI-1&2 pooled: DTG+3TC 126/716 (18%) vs. DTG+TDF/FTC 169/717 (24%)]. The frequency of AEs was generally similar across subgroups.

Table 1. Proportion of participants with plasma HIV-1 RNA <50 c/mL at week 48: Snapshot Analysis by subgroups – ITT-E population

gemini-sub-grpups

Conclusions: In GEMINI-1&2, DTG+3TC demonstrated non inferior efficacy to DTG+TDF/FTC in treatment-naïve adults with Screening HIV-1 RNA ≤500,000c/mL at Week 48. Both regimens were well tolerated. Subgroup analyses of efficacy and safety performed based on baseline disease and demographic characteristics were generally consistent with overall study results. These results further demonstrate DTG+3TC is an option for initial treatment of HIV-infected patients across a spectrum of disease characteristics and patient populations. The studies are ongoing to explore long-term durability and safety.1

  1. Orkin C, Porteiro N, Berhe M, et al. 2-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) is non-inferior to dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) at 48 weeks in antiretroviral treatment-naïve adults with HIV-1 infection: subgroup analyses in the GEMINI studies. Presented at: HIV Drug Therapy Glasgow 2018; October 28-31, 2018; Glasgow, UK.

UK/DTGP/0027/18 - November 2018