A Head-to-Head, Randomized (2:1), Open-Label, Noninferiority Trial of DOVATO vs BIKTARVY1

  • TRIAL DESIGN

    222 Adult Participants Who Started on BIKTARVY Either Switched to DOVATO or Continued BIKTARVY1

    Select Eligibility Criteria1
    • Participants virologically suppressed on BIKTARVY for ≥3 months
    • At least 2 documented measurements of HIV suppression on BIKTARVY at least 3 months apart
    • Participants ≥18 years of age
    • Stable form of insurance that was expected to continue without significant changes for at least 12 months
    Select Exclusion Criteria1
    • HBV infection or acute need for HCV therapy
    • History of prior viral failure
    • Suspected or documented INSTI resistance
    • Major NRTI resistance
    Primary Endpoint1
    • Proportion of participants with HIV-1 RNA ≥50 copies/mL at Week 48 using the FDA Snapshot algorithm (ITT–E) and a 6% noninferiority margin
    Secondary Endpoints1
    • Proportion of participants with plasma HIV-1 RNA <50 copies/mL at Weeks 48, 96, and 144 in the ITT–E population
    • Mean change in weight from baseline at Week 48, compared using 2-sample t-tests

    *Observational phase follows participants after they exit DYAD in the real world and collects 96- and 144-week efficacy and safety data recorded in the electronic medical record.1

  • BASELINE CHARACTERISTICS

    The Median Participant Was on ART for ~10 Years and Took 3 Prior ART Regimens1

    Baseline Characteristics DOVATO
    (n=149)    		 BIKTARVY
    (n=73)
    Age, median (range), years 49 (24–73) 51 (20–73)
    ≥50, n (%) 74 (50%) 44 (60%)
    Female, n (%) 24 (16%) 12 (16%)
    Race, n (%)    
    Caucasian 102 (68%) 54 (74%)
    Black 44 (30%) 18 (25%)
    Asian 1 (1%) 0 (0%)
    Ethnicity, n (%)    
    Hispanic or Latino 43 (29%) 22 (30%)
    Weight, median (range), kg 90.4 (53.1–171.9) 88.5 (59.1–123.5)
    CD4+ T-cell count, median (range), cells/mm3 720.5 (214–1479) 734.5 (151–1573)
    Duration of ART prior to Day 1, median (range), years 12 (1–32) 9.5 (1–27)
    Number of prior ART regimens 3 (1–9) 3 (1–10)
    Participants with unknown genotype, n (%) 89 (60%) 36 (49%)
    Current insurance coverage, n (%)    
    Private 132 (89) 59 (81)
    Medicare 12 (8) 10 (13)
    Medicaid 5 (3) 2 (3)
    Ryan White 0 (0) 2 (3)
    Baseline Characteristics DOVATO
    (n=149)    		 BIKTARVY
    (n=73)
    Age, median (range), years 49
    (24–73)    		 51
    (20–73)
    ≥50, n (%) 74 (50%) 44 (60%)
    Female, n (%) 24 (16%) 12 (16%)
    Race, n (%)    
    Caucasian 102 (68%) 54 (74%)
    Black 44 (30%) 18 (25%)
    Asian 1 (1%) 0 (0%)
    Ethnicity, n (%)    
    Hispanic or Latino 43 (29%) 22 (30%)
    Weight, median (range), kg 90.4
    (53.1–171.9)    		 88.5
    (59.1–123.5)
    CD4+ T-cell count, median (range), cells/mm3 720.5
    (214–1479)    		 734.5
    (151–1573)
    Duration of ART prior to Day 1, median (range), years 12 (1–32) 9.5 (1–27)
    Number of prior ART regimens 3 (1–9) 3 (1–10)
    Participants with unknown genotype, n (%) 89 (60%) 36 (49%)
    Current insurance coverage, n (%)    
    Private 132 (89) 59 (81)
    Medicare 12 (8) 10 (13)
    Medicaid 5 (3) 2 (3)
    Ryan White 0 (0) 2 (3)
    Baseline Characteristics DOVATO
    (n=149)
    Age, median (range), years 49 (24–73)
    ≥50, n (%) 74 (50%)
    Female, n (%) 24 (16%)
    Race, n (%)
    Caucasian 102 (68%)
    Black 44 (30%)
    Asian 1 (1%)
    Ethnicity, n (%)
    Hispanic or Latino 43 (29%)
    Weight, median (range), kg 90.4 (53.1–171.9)
    CD4+ T-cell count, median (range), cells/mm3 720.5 (214–1479)
    Duration of ART prior to Day 1, median (range), years 12 (1–32)
    Number of prior ART regimens 3 (1–9)
    Participants with unknown genotype, n (%) 89 (60%)
    Current insurance coverage, n (%)  
    Private 132 (89)
    Medicare 12 (8)
    Medicaid 5 (3)
    Ryan White 0 (0)
    Baseline Characteristics BIKTARVY
    (n=73)
    Age, median (range), years 51 (20–73)
    ≥50, n (%) 44 (60%)
    Female, n (%) 12 (16%)
    Race, n (%)
    Caucasian 54 (74%)
    Black 18 (25%)
    Asian 0 (0%)
    Ethnicity, n (%)
    Hispanic or Latino 22 (30%)
    Weight, median (range), kg 88.5 (59.1–123.5)
    CD4+ T-cell count, median (range), cells/mm3 734.5 (151–1573)
    Duration of ART prior to Day 1, median (range), years 9.5 (1–27)
    Number of prior ART regimens 3 (1–10)
    Participants with unknown genotype, n (%) 36 (49%)
    Current insurance coverage, n (%)  
    Private 59 (81)
    Medicare 10 (13)
    Medicaid 2 (3)
    Ryan White 2 (3)
    The study population had a median age of ~50 years, 16% female, and ~30% non-white PLHIV1

  • EFFICACY

    DOVATO Was Noninferior to BIKTARVY at 48 Weeks, With Fewer Medicines1,2

    Virologic Outcomes at Week 48 by FDA Snapshot Analysis1†

    Noninferiority criteria were not specified for the HIV-1 RNA <50 copies/mL endpoint. 

    There were no virologic data for 16 (11%) participants in the DOVATO arm and 9 (12%) participants in the BIKTARVY arm.

    †Noninferiority analysis with a 6% margin using the Farrington-Manning Score Test.1

  • RESISTANCE

    A High Barrier to Resistance and No Cases of INSTI Resistance for DOVATO Through Week 481

    Cases of CVW With Treatment-Emergent Resistance1‡§

      DOVATO
    (n=149)    		 BIKTARVY
    (n=73)
    2 consecutive viral loads ≥50 copies/mL‡ 12 (8.1%) 6 (8.2%)
    And with treatment-emergent resistance§‖ 1 1
    Cases of treatment-emergent resistance by type    
    NRTI resistance 1 1
    INSTI resistance 0 1
      DOVATO
    (n=149)
    2 consecutive viral loads ≥50 copies/mL‡ 12 (8.1%)
    And with treatment-emergent resistance §‖ 1
    Cases of treatment-emergent resistance by type
    NRTI resistance 1
    INSTI resistance 0
      BIKTARVY
    (n=73)
    2 consecutive viral loads ≥50 copies/mL‡ 6 (8.2%)
    And with treatment-emergent resistance §‖ 1
    Cases of treatment-emergent resistance by type
    NRTI resistance 1
    INSTI resistance 1

    ‡Only participants meeting CVW criteria were assessed for treatment-emergent resistance.

    §One non-CVW DOVATO participant developed SVF at Week 4 with an HIV-1 RNA of 148 copies/mL but did not return for confirmatory testing. At Week 12, HIV-1 RNA was 87 copies/mL, and a genotype was inadvertently collected at this initial episode of unconfirmed viremia. Genotypic testing demonstrated K65R, M184V, T215S, and K219E. The participant was discontinued from the trial at Week 12, at which time they had an HIV-1 RNA <50 copies/mL on DOVATO. The participant was suppressed when they discontinued DOVATO and transitioned to a DTG-based regimen (DTG + DRV/c). A baseline genotypic test demonstrated no NRTI or INSTI resistance.1

    ‖One participant in the DOVATO arm demonstrated TAMs and M184V resistance but no integrase resistance. This participant switched to a DTG-based regimen (DTG + DRV/c) and was suppressed at the time of the switch. In the BIKTARVY arm, 1 participant demonstrated M184M/I and integrase resistance (G140G/S). The participant in the BIKTARVY arm was suppressed when they discontinued from the study, and they remained on BIKTARVY.1

  • WEIGHT CHANGE DATA

    Mean Change in Weight at Week 481

    Clinical significance of these data is unknown. 

ART=antiretroviral therapy; CI=confidence interval; CVW=confirmed virologic withdrawal; DRV/c=darunavir/cobicistat; DTG=dolutegravir; HBV=hepatitis B virus; HCV=hepatitis C virus; INSTI=integrase strand transfer inhibitor; ITT–E=intent-to-treat–exposed; NRTI=nucleoside reverse transcriptase inhibitor; ns=not significant; SVF=suspected virologic failure; TAM=thymidine analogue mutation.

Reference:

  1. Rolle C-P, Castano J, Nguyen V, Hinestrosa F, DeJesus E. Efficacy, safety, and tolerability of switching from bictegravir/emtricitabine/tenofovir alafenamide to dolutegravir/lamivudine among adults with virologically suppressed HIV: the DYAD study. Open Forum Infect Dis. 2024;11(10):1-10. doi:10.1093/ofid/ofae560

PMUS-DLLWCNT240048 January 2025