Endpoints Primary proportion of patients with HIV RNA 50 cmL at W48 ITTE snapshot noninferiority if upper margin of the twosided 95 CI for the difference 4 973 power Secondary proportion of patients with HIV RNA lt 50 cmL at W48 ITTE snapshot noninferiority if lowe ID: 1018496
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1. Switch to DTG/3TCTANGO
2. DesignEndpointsPrimary: proportion of patients with HIV RNA ≥ 50 c/mL at W48 (ITT-E, snapshot) ; non-inferiority if upper margin of the two-sided 95% CI for the difference = 4%, 97.3% power Secondary: proportion of patients with HIV RNA < 50 c/mL at W48 (ITT-E, snapshot) ; non-inferiority if lower margin of the two-sided 95% CI for the difference = - 8%Switch to DTG/3TCContinue current ARTRandomisation *1 : 1Open-labelHIV+ ≥ 18 yearsStable first-line ART with TAF/FTC (TDF to TAF switch ≥ 3 months before screening allowed) + PI/b or NNRTI or INSTI≥ 2 HIV-1 RNA < 50 c/mL in the past 12 monthsHIV-1 RNA < 50 c/mL at screeningHBs Ag negativeN = 372N = 371W144W196TANGO Study: switch to DTG/3TCSwitch to DTG/3TCTANGOVan Wyk J. Clin Infect Dis 2020 Jan 6 (Epub ahead of print] * Randomisation was stratified by 3rd agent (PI, INSTI or NNRTI)
3. TANGO Study: switch to DTG/3TCDTG/3TCN = 369Continuation of current TAF/FTC-containing ARTN = 372Median age, years4039Female, %79Median time on ART, months33.835.1Median time on TAF-based ART, months17.718.2CD4 cell count (/mm3), median682720ART at randomisation, %INSTI / EVG/cNNRTI / RPVPIb / DRV78 / 6614 / 128 / 780 / 6713 / 128 / 7Discontinuation, N (%)For adverse eventFor lack of efficacyFor other reasons27 (7.3%)1301429 (7.8%)2324Excluded from per-protocol analysis, NPregnancy, N171140Baseline characteristics and patient dispositionTANGOVan Wyk J. Clin Infect Dis 2020 Jan 6 (Epub ahead of print]
4. Virologic outcome at W48ITT-e snapshotAdjusted difference (95% CI)DTG/3TC (N = 369)TAF/FTC-based ART (N = 372)0204060801000.30.593.2936.56.5HIV RNA ≥ 50 c/mLHIV RNA< 50 c/mLNo virologic data%1 discontinuation for HIV RNA ≥ 200 c/ml (TAF/FTC arm) No emergence of resistanceTAF/FTC-based ARTPrimary endpoint: HIV RNA ≥ 50 c/mLDTG/3TC-1.20.7- 0.30-2-4-6-82468Non inferioritySecondary endpoint: HIV RNA < 50 c/mLDTG/3TC - 3.4 3.90-2-4-6-82468TAF/FTC-based ART0.2Non inferiority36TANGO Study: switch to DTG/3TCTANGOVan Wyk J. Clin Infect Dis 2020 Jan 6 (Epub ahead of print]
5. Other efficacy resultsHIV RNA ≥ 50 c/mL at W48, per-protocol populationDTG/3TC = 0 vs TAF-based ART = 0.6% (difference [95% CI] : -0.6 % [- 1.3 to 0.2])Post-hoc analysis on baseline proviral DNA genotypingPre-existing archived M184V/I : 4/322 DTG/3TC and 3/321 TAF-based ARTHIV RNA < 50 c/mL at W48 in 7/7Median CD4/mm3 increase at W48DTG/3TC = + 22.5 vs TAF-based ART = + 11TANGO Study: switch to DTG/3TCVan Wyk J. Clin Infect Dis 2020 Jan 6 (Epub ahead of print] TANGO
6. DTG/3TC(N = 369)TAF/FTC-based ART(N = 372)Any adverse event, %NasopharyngitisUpper respiratory tract infectionDiarrheaHeadacheSyphilisBack painFatigueBronchitis8012887765279119754815Grade 2-5 adverse event, %51Drug-related grade 2-5 adverse event in ≥ 0,5%, %InsomniaConstipationFlatulenceHeadache11110< 100Serious adverse event, %Drug-related6040Adverse event leading to withdrawal from the study, N (%)Drug-related, N13 * (3.5)92 (0.5)1 Adverse events37TANGO Study: switch to DTG/3TCTANGO* Including anxiety (N = 3), insomnia (N = 3), weight increased (N = 2), fatigue (N = 2) Van Wyk J. Clin Infect Dis 2020 Jan 6 (Epub ahead of print]
7. Weight increase and metabolic parametersDTG/3TCN = 369Continuation of current TAF/FTC-containing ARTN = 372Adverse event of increased weight3 (0.8%)6 (1.6%)EVG/c = 2, RPV = 2, DTG = 1, RAL = 1Adjusted mean weight increase at W48+ 0.8 kg+ 0.8 kgAdjusted mean BMI increase at W48+ 0.25 kg/m2+ 0.26 kg/m2Adjusted mean HOMA-IR change- 9.7%+ 4.5%HOMA-IR ≥ 2At baselineAt W4869%65%68%74% (p = 0.008)Mean change from baseline in lipids at W48Total cholesterolHDL-cholesterolLDL-cholesterolTriglyceridesTotal cholesterol / HDL-cholesterol ratio- 4.5%- 1.2%- 5.5%- 11.2%- 3.3%+ 2.3% (p < 0.001)+ 1.7% (ns)+ 2.2% (p < 0.001)+ 6.0% (p < 0.001)+ 0.5% (p = 0.017)Van Wyk J. Clin Infect Dis 2020 Jan 6 (Epub ahead of print] TANGO Study: switch to DTG/3TCTANGO
8. Parameter%OR (95% CI)pTreatmentTAF-based regimenDTG/3TC74.164.70.59 (0.40 - 0.87)0.008SexMaleFemale69.763.20.51 (0.22 - 1.14)0.101Baseline HOMA-IRNA1.88 (1.56 - 2.27)< 0.01Baseline BMINA1.11 (1.05 - 1.17)< 0.01Variables associated with HOMA-IR ≥ 2 at W48TANGO Study: switch to DTG/3TCVan Wyk J. Clin Infect Dis 2020 Jan 6 (Epub ahead of print] TANGO
9. DTG/3TC (N = 369)TAF/FTC-based cART (N = 371)SerumUrine: proteinuria/creatininuriaRenal biomarkers at W48Adjusted mean change from baselineChange from baseline, %-10-50510eGFRcreatinine, CKD-EPI (mL/min/1.73 m2)eGFRcystatin C, CKD-EPI (mL/min/1.73 m2)Creatinine(µmol/L)6.672.19- 1.60.1- 7.7- 3.0p < 0.001p < 0.00101020-10-20-30Protein/Creatinine(g/moL)Retinol-bindingprotein/creatinine(µg/mmoL)Beta-2microglobulin/creatinine (mg/mmoL)- 2.9- 7.8- 2.71.66.36.738TANGO Study: switch to DTG/3TCTANGOVan Wyk J. Clin Infect Dis 2020 Jan 6 (Epub ahead of print]
10. TANGO Study: switch to DTG/3TCConclusionSwitching to DTG/3TC FDC was non-inferior to remaining on a TAF/FTC-based regimen through Week 48 in ART-experienced, virologically suppressed adultsNo confirmed virologic withdrawals in the DTG/3TC groupZero resistance development in the DTG/3TC groupGood safety profile of DTG/3TC FDC113TANGOVan Wyk J. Clin Infect Dis 2020 Jan 6 (Epub ahead of print]