New data from the TANGO study demonstrate the non-inferior efficacy of dolutegravir/lamivudine (DTG/3TC) compared with a tenofovir alafenamide fumarate (TAF)-containing regimen of at least 3 drugs in virally suppressed individuals with HIV-1 infection.
“With HIV now considered a chronic condition and people living with HIV needing antiretroviral treatments for life, taking fewer medicines over a lifetime has become an important consideration for the community,” Dr Kimberly Smith, head of global research & medical strategy at ViiV Healthcare, said. “The TANGO study was designed to answer the question, can a 2-drug regimen of dolutegravir/lamivudine maintain viral suppression as well as a TAF-containing regimen?”
The full 48-week results of the phase 3, randomised, open-label, active-controlled, multi-centre study were presented at the 10th IAS Conference on HIV Science (IAS 2019).
The study enrolled 743 participants who were on a TAF-containing regimen with no history of virologic failure or resistance to nucleoside reverse transcriptase inhibitors or integrase inhibitors. The participants were randomised to switch to DTG/3TC or continue on the TAF-containing regimen through week 48.
The data presented at IAS 2019 indicate that the study met its primary end point for non-inferiority based on the proportion of participants with plasma HIV-1 RNA > 50 copies per mL at week 48.
The study found that switching to DTG/3TC was non-inferior to continuing a TAF-containing regimen (snapshot virologic failure: <1% vs <1%; adjusted difference: -0.3% [95% Confidence Interval =1.2, 0.7]).
Furthermore, it is reported that the proportion of patients with plasma HIV-1 RNA <50 c/mL was both high and similar in the treatment arms and demonstrated non-inferiority (93.2% [344 of 369] of participants in DTG/3TC compared with 93% [346 of 372] in the TAF-containing regimen arm).
At 48 weeks, 0 participants in the DTG/3TC group and 1 participant in the TAF-containing regimen group met confirmed virologic failure criteria; no resistance mutations were observed at failure.
Common adverse events (AEs) included nasopharyngitis, upper respiratory tract infections, and diarrhea. The percentage of participants who withdrew due to AEs was 4% in the DTG/3TC arm vs <1% in the TAF-containing regimen arm.
DTG/3TC was approved by the US Food and Drug Administration on 8 April, 2019. The approval made DTG/3TC (Dovato) the first FDA-approved 2-drug, fixed-dose, complete regimen for treatment-naïve adults with HIV.
“These data present evidence that a dolutegravir/lamivudine 2-drug regimen is as effective as a TAF-containing, 3-drug regimen for people living with HIV,” Smith concluded.
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.
J van Wyk, F Ajana, F Bisshop, S De Wit, Y Osiyemi, J Portilla, JP Routy, C Wyen, M Ait-Khaled, M Nascimento, K Pappa, R Wang, J Wright, AR Tenorio, B Wynne, M Aboud, M Gartland, K Smith