ABSTRACT
Background: Dolutegravir/Lamivudine (DTG/3TC) 2-drug regimen (2DR) was non-inferior to a tenofovir alafenamide (TAF)-based 3-/ 4-drug regimen (3/4DR) (TBR) through the Week 48 primary endpoint in TANGO. Here we present prespecified Week 96 secondary analyses from TANGO. Method: TANGO, a randomized, open-label, non-inferiority phase III study, evaluates efficacy and safety of switching to once-daily DTG/3TC in HIV-1- infected, virologically suppressed adults vs remaining on a TBR over 148 weeks. Week 96 analysis assessed non-inferiority with a 4% non-inferiority margin for Snapshot virologic failure (VF) and 8% for virologic success (VS;US Food and Drug Administration Snapshot algorithm, intention-to- treat- exposed [ITT-E] population). Results: 741 participants were randomized/exposed (DTG/3TC: 369;TBR: 372). For Snapshot VF, switching to DTG/3TC was non-inferior to continuing TBR at Week 96 in the ITT-E analysis: 0.3% vs 1.1%;adjusted difference: -0.8% (95% CI: -2.0, 0.4) and superior to TBR in the per-protocol analysis: 0% vs 1.1%;adjusted difference: -1.1% (95% CI: -2.3, -0.0);P = 0.044 (2-sided). Snapshot VS was high in both arms (DTG/3TC: 85.9%;TBR: 79.0%;adjusted difference: 6.8% [95% CI: 1.4-12.3]). Forty-four participants (5.9%) had missing data in the Week 96 window due to COVID-19. No participants on DTG/3TC and 3 (<1%) on TBR met confirmed virologic withdrawal (CVW) criteria, with no resistance observed at failure. Overall adverse event (AE) rates were similar between arms, with more drug-related AEs in the DTG/3TC arm. Total cholesterol (TC), low-density lipoprotein cholesterol, and triglycerides improved significantly with DTG/3TC, whereas high-density lipoprotein (HDL) cholesterol changes significantly favored TBR, with no difference in TC/HDL-cholesterol ratio between arms. Decreases in glomerular filtration rate by cystatin C were observed with significantly lower decreases in the DTG/3TC arm;proximal tubular function marker changes were small and similar across arms. Conclusion: At Week 96, switching to DTG/3TC FDC was non-inferior to continuing a TAF-based 3/4DR in maintaining virologic suppression in HIV-1- infected antiretroviral therapy-experienced adults. The safety profile of DTG/3TC FDC was consistent with the DTG and 3TC respective labels. DTG/3TC 2DR offers a robust switch option with durable efficacy, good safety and tolerability, and a high barrier to resistance with zero CVWs through 96 weeks.