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.