WEAB0403LB
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Title
Switching to DTG+3TC fixed dose combination (FDC) is non-inferior to continuing a TAF-based regimen (TBR) in maintaining virologic suppression through 24 weeks (TANGO Study)
Presenter
Jean van Wyk
Authors
J. van Wyk1, F. Ajana2, F. Bisshop3, S. De Wit4, Y. Osiyemi5, J. Portilla6, J.-P. Routy7, C. Wyen8, M. Ait-Khaled1, M. Nascimento1, K. Pappa9, R. Wang9, J. Wright10, A.-R. Tenorio9, B. Wynne9, M. Aboud1, M. Gartland9, K. Smith9
Institutions
1ViiV Healthcare, Brentford, United Kingdom, 2Centre Hospitalier de Tourcoing, Tourcoing, France, 3Holdsworth House Medical Brisbane, Queensland, Australia, 4CHU St-Pierre, Brussels, Belgium, 5Triple O Research Institute PA, West Palm Beach, United States, 6Hospital General Universitario de Alicante, Alicante, Spain, 7McGill University Health Center, Montreal, Canada, 8Praxis am Ebertplatz, Cologne, Germany, 9ViiV Healthcare, Research Triangle Park, United States, 10GlaxoSmithKline, Stockley Park, United Kingdom

Background: DTG+3TC 2-drug regimen (2DR) is noninferior to DTG+TDF/FTC 3 drug regimen in HIV-1 infected ART-naïve adults. Efficacy and safety of switching to DTG+3TC in ART-experienced adults suppressed on 3DRs have been demonstrated in smaller studies.
Methods: TANGO, a randomized, open-label, multicenter, non-inferiority Phase III study evaluates efficacy and safety of switching to DTG+3TC once daily in HIV-1 infected adults on TBR with HIV-1 RNA< 50c/mL for > 6 months, without prior virologic failure, no historical NRTI or INSTI major resistance mutations. Participants were randomized 1:1 (stratified by baseline 3rd agent class: PI, NNRTI, INI) to switch to DTG+3TC or continue TBR through Wk148. Primary endpoint: proportion of participants with plasma HIV-1 RNA≥50c/mL at Week 48 (FDA Snapshot algorithm) for Intention To Treat-Exposed (ITT-E) population. Planned Wk24 interim analysis assessed non-inferiority of DTG+3TC with 4% non-inferiority (NI)margin. Secondary endpoint: Virologic suppression (HIV-1 RNA< 50c/mL by FDA Snapshot, ITT-E) with 8% NI margin.
Results: 741 randomized/exposed participants (DTG+3TC: 369; TBR: 372). demonstrated switching to DTG+3TC was non-inferior to continuing TBR at Week 24 - Snapshot Virologic Failure: < 1% vs. < 1%; adjusted difference: -0.5% (95% CI: -1.6%, 0.5%). Proportion with plasma HIV-1 RNA< 50 c/mL was high and similar in both arms and demonstrated non-inferiority (Table 1). Zero participant on DTG+3TC and 1 participant (< 1%) on TBR met protocol-defined virologic failure with no resistance mutations observed at failure. No unexpected AEs were identified for DTG or 3TC.

Week 24 Study Outcome by Snapshot Analysis (ITT-E Population)DTG + 3TC (N=369) n (%)TBR (N=372) n (%)
HIV-1 RNA ≥50 c/mL (Snapshot Virologic Failure)1 (<1)3 (<1)
HIV-1 RNA <50 c/mL (Snaphot Virologic Success) a 350 (95)358 (96)
No Virologic Data at Week 24 Window18 (5)11 (3)
Key Safety results (Safety Population)(N=369)(N=371b)
AEs or death leading to withdrawal c 12 (3)1 (<1)
Drug-related Grade 2-5 AEs c 15 (4)3 (<1)
Serious Adverse Events (none related to study treatment)14 (4)8 (2)
a Snapshot Virologic Success adjusted difference in (DTG+3TC) - TBR: -1.4% (95% CI: -4.4%, 1.6%). Estimates and confidence intervals were based on a stratified analysis using Cochran-Mantel-Haenszel weights adjusting for baseline 3rd agent class. b One subject was excluded due to receiving a TDF-based regimen instead of a TAF-based regimen c One death (homicide) unrelated to treatment occurred in the DTG+3TC arm.
[Efficacy and Key Safety Results for the ITT-E and Safety Population]


Conclusions: At Wk24, switching to DTG/3TC FDC was non-inferior to continuing a TAF-based 3DR 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 new robust switch option with reduced ART exposure, without increased risk of virologic failure or resistance. The study is ongoing; conference presentation will include Wk48 results.