Switching to dolutegravir/lamivudine dual therapy is non-inferior to TAF-based triple therapy at week-48 in TANGO study
Simon Collins, HIV i-Base
Results from a international phase 3 study using the dual fixed dose combination (FDC) dolutegravir/lamivudine (DTG/3TC) as a switch option in treatment experienced participants was presented in a late-breaking oral presentation at IAS 2019.
Although already approved for first-line therapy, the phase 3 TANGO study is the first large randomised study to look at this in treatment-experienced participants.
This study randomised 741 people (1:1) with viral load <50 copies/mL for > 6 months on current TAF-based ART to either switch to DTG/3TC or remain on their current therapy. Entry criteria included not having hepatitis B or prior virologic failure or document major resistance to NRTIs or integrase inhibitors.
The primary endpoint of this ongoing phase 3, non-inferiority trial is viral suppression at week-48, with results stratified by baseline third drug (PI, NNRTI or INSTI), with follow-up out to week 196.
Approximate baseline characteristics included median (range) age 40 years (18 to 74), which 20% older than 50; 8% were women and 20% were defined as “non-white”. Baseline median (range) CD4 was about 700 cells/mm3 (119 to 1904) with 9% having a CD4 count <350 cells/mm3.
Most participants were using an integrase inhibitor (79%, mainly elvitegravir), with 14% using an NNRTI (mainly rilpivirine) and 7% were using a boosted PI (mainly boosted darunavir).
Participants had been on ART for a median (range) of 34 months (range: 7 to 201 months).
At week 48, 0.3% vs 0.5% (n=1 and 2) participants had viral load >50 copies/mL in the dual vs triple arms respectively (difference: 0.3: 95%CI: 1.2 to +0.7), meeting criterion for non-inferiority for this primary endpoint, based on 4% margin. The single case in the DTG/3TC arm was a protocol violation before taking study drugs.
Results were very similar for secondary endpoint of suppression < 50 copies/mL: 93% in each arm, again meeting non-inferiority (difference: 0.2; 95%CI: –3.4 to +3.9, margin 8%). Also, 6.5% in each group had no data for this time point. See Table 1.
Adverse events were similar between groups: with 80% reporting any AE, but 12% vs 1% reported drug-related AEs, in the dual vs TDF arms, with 4% (n=13) vs 1% (n=2) discontinuing because of side effects. These were mainly anxiety (n=3), insomnia (n=3), weight gain (n=2) or fatigue (n=2) in the DTG/3TC arm (all (<1%). Serious AEs (SAEs) were report by 6% (n=21) vs 4% (n=16). The single death in the study was due to gunshot wounds and unrelated to HIV treatment.
Small differences in bone and renal markers, and lipid profiles, were unlikely to have clinical significance but continued follow-up to 96- and 148 weeks will provide information about longer-term results.
At week 48, similar weight gains were reported for each group (approximately +0.8 kg).
Table 1: Week 48 study outcome by snapshot analysis
|TAF-based ART (n=372)|
|VL <50 c/mL, n (5)||344 (93%)||346 (93%)|
|VL <50 c/mL, n (5)||1* (0.3%)||2 (0.5%)|
|No VL data||24 (6.5%)||24 (6.5%)|
|Discontinue (AE or death)||12 (3.3%)||1 (0.3%)|
|Discontinue other reasons (VL >50 c/mL||24 (6.5%)||22 (5.9%)|
* Discontinued unrelated to treatment.
van Wyk J et al. 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). 10th IAS Conference on HIV Science (IAS 2019), 21-24 July 2019, Mexico City. Late-breaker oral abstract WEAB0403LB.