A Trial That Studied Switching to DOVATO from TAF-Containing Regimens Through 196 Weeks

See the data on virologically suppressed patients switching to fewer ARVs than a 3DR. Consider the switch.

  • TRIAL DESIGN

    TANGO Trial Through 196 Weeks

    Select Eligibility Criteria1,2*
    • Virologically suppressed adults with HIV-1 RNA <50 copies/mL for >6 months
    • Stable 3- or 4-drug TAF-containing regimen: TAF/FTC + INSTI, NNRTI, or PI as initial treatment regimen
    • No history of virologic failure
    • No documented NRTI or INSTI resistance
    • No severe hepatic impairment (Child-Pugh class C)
    • HBV negative
    Primary Endpoint1,4

    Proportion of participants with HIV-1 RNA ≥50 copies/mL at Week 48 using FDA Snapshot analysis (ITT–E) with a 4% noninferiority margin.

    Secondary Endpoint1,4

    Proportion of participants with HIV-1 RNA ≥50 copies/mL and <50 copies/mL by Snapshot algorithm, ITT–E (4% noninferiority margin for ≥50 copies/mL and 8% noninferiority margin for <50 copies/mL) at 96 weeks and 144 weeks.

    Early and Late Switch3

    Patients who switched to DOVATO at Week 1 are referred to as the Early-Switch group. Patients in the TAF-containing regimens arm were switched to DOVATO at Week 148 if HIV-1 RNA <50 copies/mL (N=298) (Late-Switch group).

    *Baseline third-agent class, TAF-containing regimens included TAF/FTC plus: 79.6% INSTI (n=296 [DTG n=41]; RAL n=6; EVG/c n=249]); 12.9% NNRTI (n=48; RPV n=45); 7.5% PI (n=28; bDRV n=27).1,4

  • BASELINE CHARACTERISTICS

    TANGO Baseline Characteristics1,2,4

      DOVATO
    (N=369), n (%)    		 TAF-Containing Regimens
    (N=372), n (%)
    Median age (range) 40 years (20–74) 39 years (18–73)
    Female 25 (7%) 33 (9%)
    African American or African heritage 50 (14%) 58 (16%)
    Asian 13 (4%) 13 (4%)
    White 297 (81%) 289 (78%)
    Hispanic or Latino 69 (19%) 66 (18%)
    Median CD4+ T-cell count (range), cells/mm3 682 (133–1904) 720 (119–1810)
    CD4+ T-cell count <200 cells/mm3 7 (2%) 7 (2%)
    CDC Stage 3 (AIDS) 20 (5%) 19 (5%)
    ≥1 ART stopped or switched prior to screening (any medication) 220 (60%) 244 (66%)
      DOVATO
    (N=369), n (%)    		 TAF-Containing Regimens
    (N=372), n (%)
    Median age (range) 40 years (20–74) 39 years (18–73)
    Female 25 (7%) 33 (9%)
    African American or African heritage 50 (14%) 58 (16%)
    Asian 13 (4%) 13 (4%)
    White 297 (81%) 289 (78%)
    Hispanic or Latino 69 (19%) 66 (18%)
    Median CD4+ T-cell count (range), cells/mm3 682
    (133–1904)    		 720
    (119–1810)
    CD4+ T-cell count <200 cells/mm3 7 (2%) 7 (2%)
    CDC Stage 3 (AIDS) 20 (5%) 19 (5%)
    ≥1 ART stopped or switched prior to screening (any medication) 220 (60%) 244 (66%)
      DOVATO
    (N=369), n (%)
    Median age (range) 40 years (20–74)
    Female 25 (7%)
    African American or African heritage 50 (14%)
    Asian 13 (4%)
    White 297 (81%)
    Hispanic or Latino 69 (19%)
    Median CD4+ T-cell count (range), cells/mm3 682 (133–1904)
    CD4+ T-cell count <200 cells/mm3 7 (2%)
    CDC Stage 3 (AIDS) 20 (5%)
    ≥1 ART stopped or switched prior to screening (any medication) 220 (60%)
      TAF-Containing Regimens
    (N=372), n (%)
    Median age (range) 39 years (18–73)
    Female 33 (9%)
    African American or African heritage 58 (16%)
    Asian 13 (4%)
    White 289 (78%)
    Hispanic or Latino 66 (18%)
    Median CD4+  T-cell count (range), cells/mm3 720 (119–1810)
    CD4+  T-cell count <200 cells/mm3 7 (2%)
    CDC Stage 3 (AIDS) 19 (5%)
    ≥1 ART stopped or switched prior to screening (any medication) 244 (66%)
    Median duration of ART before Day 1 was >2.5 years1†

    †33.8 months and 35.1 months for the DOVATO arm and TAF-containing regimens arm, respectively.

  • EFFICACY

    Demonstrated Noninferior Efficacy Through 144 Weeks and Durability Through 196 Weeks1-3

    144-Week Noninferior Efficacy vs TAF-Containing Regimens

    Durable Suppression
Through 4 Years

    Durable Suppression
Through 4 Years

    ‡The number of participants with no virologic data at Week 96 due to COVID-19 (14% for the DOVATO arm and 20% for the TAF-containing regimens arm) was a primary driver in the treatment difference in the secondary endpoint.2

  • RESISTANCE

    A Demonstrated High Barrier to Resistance

     

    Confirmed Virologic Withdrawal, n (%)2,3§II
      DOVATO‖ (N=369) TAF-Containing Regimens‖ (N=372)
    Week 48 0 1 (<1)
    Week 96 0 3 (<1)
    Week 144 0 3 (<1)
    Week 196 1 (<1) NA

    Confirmed Virologic Withdrawal, n (%)2,3§II
      DOVATO‖ (N=369) TAF-Containing Regimens‖ (N=372)
    Week 48 0 1 (<1)
    Week 96 0 3 (<1)
    Week 144 0 3 (<1)
    Week 196 1 (<1) NA

    Confirmed Virologic Withdrawal, n (%) 2,3§II

      DOVATO ‖ (N=369)
    Week 48 0
    Week 96 0
    Week 144 0
    Week 196 1 (<1)
      TAF-Containing Regimens ‖ (N=372)
    Week 48 1 (<1)
    Week 96 3 (<1)
    Week 144 3 (<1)
    Week 196 NA

    §CVW was defined as HIV-1 RNA ≥50 copies/mL followed by a second consecutive HIV-1 RNA ≥200 copies/mL. Only participants meeting CVW criteria (1 for DOVATO, 3 for TCR) were evaluated for treatment-emergent resistance.2

    ‖Of the participants in both arms, none had treatment-emergent resistance.2,4

    Patients in the TAF-containing regimens arm were switched to DOVATO at Week 148 if HIV-1 RNA <50 copies/mL (Late Switch).3

  • METABOLIC DATA

    Change From Baseline at 144 Weeks in Serum Lipids6

    Prespecified Secondary Endpoint

    Clinical significance of these data is unknown

    #Subjects on lipid-modifying agents at baseline were excluded (DOVATO: 13%; TCR: 15%). Lipid last observation carried forward data were used such that the last available fasted, on-treatment lipid value prior to the initiation of a lipid-lowering agent was used in place of future observed values.4,6

    Change From Baseline at 144 Weeks in Renal Function

    Prespecified Secondary Endpoint**

    Clinical significance of these data is unknown

    **Adjusted for treatment, baseline third-agent class, baseline CD4+ T-cell count, age, sex, race, BMI, presence of diabetes, presence of hypertension, and baseline marker value.4

    ††Based on estimated geometric means ratio of Week 144 vs baseline. Based on the same model as plasma/serum markers except adjusting for loge-transformed baseline marker.2

    n=number of participants with nonmissing data at baseline and Week 144.

3DR=3-drug regimen; ART=antiretroviral therapy; ARV=antiretroviral; bDRV=boosted darunavir; BMI=body mass index; CI=confidence interval; CKD-EPI=Chronic Kidney Disease Epidemiology Collaboration; CVW=confirmed virologic withdrawal; DTG=dolutegravir; eGFR=estimated glomerular filtration rate; ES=Early Switch; EVG/c=elvitegravir/cobicistat; FTC=emtricitabine; HBV=hepatitis B virus; HDL=high-density lipoprotein; INSTI=integrase strand transfer inhibitor; ITT–E=intent-to-treat–exposed; LDL=low-density lipoprotein; NNRTI=non-nucleoside reverse transcriptase inhibitor; NRTI=nucleoside reverse transcriptase inhibitor; PI=protease inhibitor; RAL=raltegravir; RPV=rilpivirine; SE=standard error; TAF=tenofovir alafenamide; TCR=TAF-containing regimen.

References:

  1. van Wyk J, Ajana F, Bisshop F, et al. Efficacy and safety of switching to dolutegravir/lamivudine fixed-dose 2-drug regimen vs continuing a tenofovir alafenamide-based 3- or 4-drug regimen for maintenance of virologic suppression in adults living with human immunodeficiency virus type 1: phase 3, randomized, noninferiority TANGO study. Clin Infect Dis. 2020;71(8):1920-1929. doi:10.1093/cid/ciz1243
  2. Osiyemi O, De Wit S, Ajana F, et al. Efficacy and safety of switching to dolutegravir/lamivudine (DTG/3TC) versus continuing a tenofovir alafenamide-based 3- or 4-drug regimen for maintenance of virologic suppression in adults living with HIV-1: results through week 144 from the phase 3, noninferiority TANGO randomized trial. Clin Infect Dis. 2022;75(6):975-986. doi:10.1093/cid/ciac036
  3. De Wit S, Bonnet F, Osiyemi O, et al. Durable efficacy of switching from a 3- or 4-drug tenofovir alafenamide–based regimen to the 2-drug regimen dolutegravir/lamivudine in the TANGO study through week 196. J Acquir Immune Defic Syndr. 2024;96(2):156-160. doi:10.1097/QAI.0000000000003395
  4. Data on file, ViiV Healthcare.
  5. Wang R, Wright J, Ait-Khaled M, et al. Assessing the virologic impact of archived resistance in an HIV-1 switch study TANGO through week 48. Presented at: CROI; March 8-11, 2020; Boston, MA. Poster 489.
  6. van Wyk J, Ait-Khaled M, Santos J, et al. Metabolic health outcomes at week 144 in the TANGO study, comparing a switch to DTG/3TC versus maintenance of TAF-based regimens. Presented at: 11th IAS Conference on Science; July 18-21, 2021; Virtual. Poster PEB164.

PMUS-DLLWCNT240050 January 2025