GEMINI-1 AND GEMINI-2 STUDIES

GEMINI-1 and GEMINI-2 are identical ongoing double-blind, non-inferiority Phase 3 studies.

Participants were treatment-naïve adults with HIV-1 (N=1433). Participants were randomised 1:1 to DTG + 3TC or DTG + TDF/FTC up until Week 96, with primary analysis taking place at Week 48), followed by an open-label, randomised phase from Week 96 up until Week 148.

Study design:1
GEMINI-1 and GEMINI-2 study design illustration
Primary endpoint:1,2

Proportion of patients with plasma HIV-1 RNA <50 copies/mL at Week 48 as determined with the FDA snapshot analysis algorithm in the ITT-E population (-10% non-inferiority margin).

 

Endpoints for the Week 96 secondary analysis:1

  • Proportion of patients with HIV-1 RNA <50 copies/mL at Week 96
  • Change in CD4+ cell count from baseline
  • Incidence of emergent mutations conferring genotypic and/or phenotypic resistance to DTG+3TC or DTG + TDF/FTC in participants with confirmed viral withdrawal
  • Proportion of patients with HIV-RNA <50 copies/mL in subgroups defined by demographic and baseline disease characteristics, including plasma viral load and CD4+ cell count
  • Incidence and severity of AEs and proportion of patients who discontinued due to AEs
Results/outcomes:1,2
  • Rapid, powerful and durable non-inferior efficacy in treatment-naïve adults
  • 72% of patients in the DTG + 3TC group vs 70% of patients in the DTG + TDF/FTC group were suppressed at Week 4
  • 91% of patients in the DTG + 3TC group vs 93% of patients in the DTG + TDF/FTC group were suppressed at Week 48 (primary endpoint)
  • 82% of patients in the DTG + 3TC group vs 84% of patients in the DTG + TDF/FTC group were suppressed at Week 144
     
  • Low rates of confirmed virological withdrawal though Week 144
    • Few confirmed virological withdrawals on DTG+3TC (12 [2.0%]) vs DTG + TDF/FTC (9 [1.0%])
    • 1 non-CVW participant with reported non-adherence in the DTG + 3TC group developed M184V at Week 132 (HIV-1 RNA 61,927 c/mL) and R263R/K at Week 144 (HIV-1 RNA 135 c/mL), conferring a 1.8-fold change in susceptibility to DTG
      • Suppressed to HIV-1 RNA <50 c/mL from Week 4 through Week 120; HIV-1 RNA 61,927 c/mL detected at Week 132, with successive HIV-1 RNA of <50, 135, and 61 c/mL after Week 132
      • Withdrawn due to lack of efficacy after Week 144, switched to DTG once daily + DRV/COBI, and regained virologic suppression

  • DTG was generally well tolerated up to 144 weeks
    • Overall AE profiles were similar between treatment groups
    • Lower risk of drug-related AEs in the DTG + 3TC group through Week 144
      • Participants in the DTG + 3TC group had a significantly lower risk of drug-related AEs (20%) compared with the DTG + TDF/FTC group for the pooled population (27%; relative risk, 0.76 [95% CI, 0.63-0.92])
         
  • Changes in renal and bone biomarkers significantly favoured DTG + 3TC at Week 144
  • Improvements in TC:HDL ratio in both arms at 144 weeks

N.B. The GEMINI studies did not determine whether these changes translate to clinical differences

References:

  1. Cahn P, et al. J Acquir Defic Synd. 2020;83(3):310–318.
  2. Cahn P, et al. HIV Drug Therapy. Presented at: HIV Glasgow 2020; October 5-8, 2020; Virtual. Poster P018.
DOVATO (Dolutegravir/lamivudine)

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