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

Abstract

Background The 2-drug regimen dolutegravir (DTG) + lamivudine (3TC) is indicated for treatment-naive adults with human immunodeficiency virus type 1 (HIV-1). We present efficacy and safety of switching to DTG/3TC in virologically suppressed individuals. Methods TANGO is an open-label, multicenter, phase 3 study that randomized adults (1:1, stratified by baseline third agent class) with HIV-1 RNA <50 copies/mL to switch to once-daily fixed-dose DTG/3TC or remain on a tenofovir alafenamide (TAF)–based regimen. The primary end point was proportion of participants with HIV-1 RNA ≥50 copies/mL at week 48 (US Food and Drug Administration Snapshot algorithm) in the intention-to-treat–exposed population (4% noninferiority margin). Results 743 adults were enrolled; 741 received ≥1 dose of study drug (DTG/3TC, N = 369; TAF-based regimen, N = 372). At week 48, proportion of participants with HIV-1 RNA ≥50 copies/mL receiving DTG/3TC was 0.3% (1/369) vs 0.5% (2/372) with a TAF-based regimen (adjusted treatment difference [95% confidence interval], −0.3 [−1.2 to .7]), meeting noninferiority criteria. No participants receiving DTG/3TC and 1 receiving a TAF-based regimen met confirmed virologic withdrawal criteria, with no emergent resistance at failure. Drug-related grade ≥2 adverse events and withdrawals due to adverse events occurred in 17 (4.6%) and 13 (3.5%) participants with DTG/3TC and 3 (0.8%) and 2 (0.5%) with a TAF-based regimen, respectively. Conclusions DTG/3TC was noninferior in maintaining virologic suppression vs a TAF-based regimen at week 48, with no virologic failure or emergent resistance reported with DTG/3TC, supporting it as a simplification strategy for virologically suppressed people with HIV-1. Clinical Trials Registration NCT03446573.

Evaluation of the Efficacy and Tolerability of Dolutegravir Plus Lamivudine as a Switch Strategy in Treatment-experienced HIV-infected Patients

“…Although the changes in serum creatine and eGFR have been statistically signi cant at 48 weeks after the switching, they are proved not to be related to a real decrease in glomerular ltration [21]. These are substantially similar to previous ndings using the same drug combination [9,16]. This change could be due to the long-term use of DTG on organic cation transporter 2 (OCT2), which provides a mechanistic basis for the mild increases in serum creatinine [21,22].…”

“…The combination of DTG with 3TC has been proved in several other studies with rapid and sustained virological suppression in ART-naive patients in the PADDLE [8] and GEMINI-1 and GEMINI-2 [9] trials. In patients with sustained HIV virological suppression from the TANGO trial, switching to treatment with DTG plus 3TC was non-inferior to a TAFbased regimen at 48 weeks [16]. Several real-life studies also demonstrated that 3TC plus DTG was a safe and effective option for the simpli cation of ART in pretreated and virologically stable HIV-positive patients, being the same effectiveness as the triple therapy it replaces [17][18][19].…”

Long-Acting Injectable Cabotegravir + Rilpivirine for HIV Maintenance Therapy: Week 48 Pooled Analysis of Phase 3 ATLAS and FLAIR Trials

“…This proportion is comparable to other large switch studies, which also reported incidences of ≤1%. 22 , 23 Excluding the 1 participant who discontinued oral lead-in dosing because of a false-positive pregnancy test, all of these participants had NNRTI (n = 6) and/or INSTI (n = 4) resistance-associated mutations at time of suspected virologic failure. All except 1 (ATLAS, subtype AG) of these participants were subtype A1 or A.…”

Shall We Dance? Extending TANGO’s Results to Clinical Practice

“…To the Editor —After previous evidence from the ASPIRE trial [ 1 ], results from the TANGO study [ 2 ] definitively proved the efficacy of lamivudine (3TC) plus dolutegravir (DTG) as a maintenance strategy. As trials’ populations often differ from real-practice settings, we aimed to assess whether these results are reproducible in an unselected population living with human immunodeficiency virus (HIV).…”