GEMINI 1 & 2 Studied >1400 Patients in a Treatment-Naïve Setting Through 144 Weeks

Choose a treatment option for now and later.

  • TRIAL DESIGN

    GEMINI 1 & 2: Studied >1400 Treatment-Naïve Adults Through 144 Weeks2,3

    GEMINI 1 & 2 (Pooled): Phase 3, Identically Designed, Double-Blind, Noninferiority Trials

    Select Eligibility Criteria
    • Treatment-naïve adults ≥18 years old
    • HBV negative
    • HIV-1 RNA 1000 copies/mL to ≤500,000 copies/mL at screening
    • CrCl ≥50 mL/min
    • No severe hepatic impairment (Child-Pugh class C)
    • No evidence of major resistance-associated mutations (<1% of screened participants had M184V mutation at baseline and were excluded)
    Primary Endpoint2

    Proportion of participants with HIV-1 RNA <50 copies/mL at Week 48 (by FDA Snapshot algorithm, ITT–E with a 10% noninferiority margin)

    Secondary Endpoint3

    Proportion of participants with plasma HIV-1 RNA <50 copies/mL at Weeks 96 and 144 (by FDA Snapshot algorithm for the ITT–E with a 10% noninferiority margin)

  • BASELINE CHARACTERISTICS

    GEMINI Baseline Characteristics (Pooled)2

      DOVATO (N=716), n (%) DTG + TDF/FTC (N =717), n (%)
    Median age 32 years 33 years
    Female 113 (16%) 98 (14%)
    African American or African heritage 99 (14%) 76 (11%)
    White 480 (67%) 497 (69%)
    Asian 71 (10%) 72 (10%)
    HIV-1 RNA >100,000 copies/mL* 140 (20%) 153 (21%)
    CD4+ T-cell count ≤200 cells/mm3 63 (9%) 55 (8%)
    CDC Stage 3 (AIDS) 66 (9%) 60 (8%)
    HCV co-infection 39 (5%) 49 (7%)
      DOVATO (N=716), n (%) DTG + TDF/FTC (N =717), n (%)
    Median age 32 years 33 years
    Female 113 (16%) 98 (14%)
    African American or African heritage 99 (14%) 76 (11%)
    White 480 (67%) 497 (69%)
    Asian 71 (10%) 72 (10%)
    HIV-1 RNA >100,000 copies/mL* 140 (20%) 153 (21%)
    CD4+ T-cell count ≤200 cells/mm3 63 (9%) 55 (8%)
    CDC Stage 3 (AIDS) 66 (9%) 60 (8%)
    HCV co-infection 39 (5%) 49 (7%)
      DOVATO (N=716), n (%)
    Median age 32 years
    Female 113 (16%)
    African American or African heritage 99 (14%)
    White 480 (67%)
    Asian 71 (10%)
    HIV-1 RNA >100,000 copies/mL† 140 (20%)
    CD4+ T-cell count ≤200 cells/mm3 63 (9%)
    CDC Stage 3 (AIDS) 66 (9%)
    HCV co-infection 39 (5%)
      DTG + TDF/FTC
    (N =717), n (%)
    Median age 33 years
    Female 98 (14%)
    African American or African heritage 76 (11%)
    White 497 (69%)
    Asian 72 (10%)
    HIV-1 RNA >100,000 copies/mL† 153 (21%)
    CD4+ T-cell count ≤200 cells/mm3 55 (8%)
    CDC Stage 3 (AIDS) 60 (8%)
    HCV co-infection 49 (7%)

    *2% of participants in each arm had baseline HIV-1 RNA ≥500,000 copies/mL.2

  • EFFICACY

    Proven, Sustained Virologic Suppression Through 144 Weeks1,2,4

    GEMINI 1 & 2—DOVATO Was Noninferior to DTG + TDF/FTC at 48, 96, and 144 Weeks

    Pooled Virologic Response (ITT–E; Snapshot analysis)

    The evaluation of antiviral activity over time was a prespecified secondary endpoint, ITT–E population.

    DOVATO Virologic Suppression

    Post Hoc Analysis: Participants With HIV-1 RNA <50 copies/mL at Week 144, by Adherence Category5†

    Participants Were Stratified by ≥90% vs <90% Adherence

    Methods
    • Association between adherence and virologic suppression was evaluated at Week 144 using FDA Snapshot
    • Adherence (%) was calculated as the number of pills taken (pills returned subtracted from pills available) per number of pills prescribed, estimated using pill count data
    FDA Snapshot Treatment Difference
    • ≥90% adherence: –2.6% (95% CI; –7.9%, 2.7%); <90% adherence: 1.8% (95% CI; –21.5%, 25.9%)
    Limitations
    • Small number of participants in the lower adherence subgroup (5% in both arms)
    • Utilizing pill count to accurately measure adherence
    • Increase in number of patients with no virologic data since Week 48 due to COVID-19

    †Results from post hoc analysis are descriptive only.

  • RESISTANCE

    High Barrier to Resistance Through 144 Weeks in Treatment-Naïve Adults1

      CVW‡ (Cumulative) All Participants With Treatment-Emergent Mutations
    DOVATO (N=716), n 12 1§
    DTG + TDF/FTC (N =717), n 9 0
      CVW‡ (Cumulative) All Participants With Treatment-Emergent Mutations
    DOVATO (N=716), n 12 1§
    DTG + TDF/FTC (N =717), n 9 0
      CVW ‡ (Cumulative)
    DOVATO (N=716), n 12
    DTG + TDF/FTC (N =717), n 9
      All Participants With Treatment-Emergent Mutations
    DOVATO (N=716), n 1 §
    DTG + TDF/FTC (N =717), n 0

    ‡CVW—defined as either virologic nonresponse (a decrease in plasma HIV-1 RNA of <1 log10 copies/mL by Week 12, with subsequent confirmation, unless plasma HIV-1 RNA is <200 copies/mL or confirmed plasma HIV-1 RNA ≥200 copies/mL on or after Week 24) or virologic rebound (confirmed rebound in plasma HIV-1 RNA levels to ≥200 copies/mL after prior confirmed suppression to <200 copies/mL).2

    §1/716 in the DOVATO arm developed treatment-emergent resistance (M184V at Week 132 and R263R/K at Week 144). In the DTG + TDF/FTC arm, there were no resistance mutations observed among participants.1

    In 12 Cases of Confirmed Virologic Withdrawal, Viral Rebound Did Not Lead to Resistance3

Cl=confidence interval; CrCl=creatinine clearance; CVW=confirmed virologic withdrawal; DTG=dolutegravir; FTC=emtricitabine; HBV=hepatitis B virus; HCV=hepatitis C virus; INSTI=integrase strand transfer inhibitor; ITT–E=intent-to-treat–exposed; NRTI=nucleoside reverse transcriptase inhibitor; TDF=tenofovir disoproxil fumarate.

References:

  1. Cahn P, Madero JS, Arribas JR, et al. Three-year durable efficacy of dolutegravir plus lamivudine in antiretroviral therapy-naïve adults with HIV-1 infection. AIDS. 2022;36(1):39-48. doi:10.1097/QAD.0000000000003070
  2. Cahn P, Madero JS, Arribas JR, et al; GEMINI Study Team. Dolutegravir plus lamivudine versus dolutegravir plus tenofovir disoproxil fumarate and emtricitabine in antiretroviral-naïve adults with HIV-1 infection (GEMINI-1 and GEMINI-2): week 48 results from two multicentre, double-blind, randomised, non-inferiority, phase 3 trials. Lancet. 2019;393(10167):143-155. doi:10.1016/S0140-6736(18)32462-0
  3. Data on file, ViiV Healthcare.
  4. Cahn P, Madero JS, Arribas JR, et al. Durable efficacy of dolutegravir plus lamivudine in antiretroviral treatment-naïve adults with HIV-1 infection: 96-week results from the GEMINI-1 and GEMINI-2 randomized clinical trials. J Acquir Immune Defic Syndr. 2020;83(3):310-318. doi:10.1097/QAI.0000000000002275
  5. Fernvik E, Madero JS, Espinosa N, et al. Impact of treatment adherence on efficacy of DTG + 3TC and DTG + TDF/FTC: pooled week 144 analysis of the GEMINI-1 and GEMINI-2 clinical studies. Presented at: 18th European AIDS Conference; October 27-30, 2021; Virtual. Poster PE2/63.

PMUS-DLLWCNT240051 January 2025