Switching to DTG/3TC fixed-dose combination (FDC) is non-inferior to continuing a TAF-based regimen (TBR) in maintaining virologic suppression through 96 weeks (TANGO study)

Background: DTG/3TC two-drug regimen (2DR) was non-inferior to a TAF-based 3/4DR through the Week 48 primary endpoint in TANGO Here we present Week 96 secondary endpoint analyses Materials and methods: TANGO, a randomized, open-label, non-inferiority phase III study evaluates the efficacy and safety of switching to once-daily DTG/3TC in HIV-1-infected, virologically suppressed (\u003e6 months, no prior virologic failure, no major NRTI or INSTI resistance) adults versus remaining on a TBR, over 148 weeks Participants were randomized 1:1, stratified by baseline third agent class: PI, NNRTI, INSTI Week 96 analysis assessed non-inferiority with a 4% non-inferiority margin for Snapshot virologic failure (VF) and 8% for virologic success (VS;FDA Snapshot algorithm, intention-to-treat-exposed [ITT-E] population) Results: Seven hundred and forty-one randomized/exposed participants (DTG/3TC: 369;TBR: 372) For Snapshot VF, switching to DTG/3TC was non-inferior to continuing TBR at Week 96 in the ITT-E analysis: 0 3% versus 1 1%;adjusted difference:-0 8% (95% CI-2 0%, 0 4%) and superior to TBR in the per-protocol analysis: 0% versus 1 1%;adjusted difference:-1 1% (95% CI-2 3%,-0 0%);p = 0 044 (twosided) Snapshot VS was high in both arms and demonstrated non-inferiority (Table 1) Forty-four participants (5 9%) had missing data in the Week 96 window due to COVID-19 impact Zero participants on DTG/3TC and three (\u003c1%) on TBR met protocol-defined VF with no resistance observed at failure Overall adverse event (AE) rates were similar between arms, with more drug-related AEs in the DTG/3TC arm (Table 1) TC, LDL-cholesterol, and triglycerides improved significantly with DTG/3TC while HDL-cholesterol (HDL-C) changes significantly favored TBR, with no difference in TC/HDL-C ratio between arms Decreases in GFR by cystatin C were observed with a significantly lower decrease in the DTG/3TC arm;proximal tubular function marker changes were small and similar across arms aSnapshot virologic success adjusted difference in (DTG/3TC)-TBR: 6 8% (95% CI 1 4%, 12 3%) Estimates and confidence intervals were based on a stratified analysis using Cochran-Mantel-Haenszel weights adjusting for baseline third agent class;bsensitivity analysis excluding 16 and 28 participants in the DTG/3TC and TBR arms, respectively, because of no Week 96 HIV-1 RNA data due to COVID-19 pandemic impact Snapshot virologic success adjusted difference in (DTG/3TC)-TBR: 4 3% (95% CI-0 6%, 9 2%);cone participant was excluded due to receiving a TDF-based regimen instead of a TAF-based regimen;dtwo deaths (one homicide and one unknown reason) both unrelated to treatment occurred in the DTG/3TC arm Conclusions: At Week 96, switching to DTG/3TC FDC was non-inferior to continuing a TAF-based 3/4DR in maintaining virologic suppression in HIV-1-infected ART-experienced adults The safety profile of DTG/3TC FDC was consistent with the DTG and 3TC respective labels DTG/3TC 2DR offers a robust switch option with durable efficacy, good safety and tolerability, and a high barrier to resistance with zero protocol-defined VF through 96 weeks