ABSTRACT
BACKGROUND: In TANGO, switching to dolutegravir/lamivudine (DTG/3TC) demonstrated long-term non-inferior efficacy vs continuing tenofovir alafenamide-based regimens in treatment-experienced adults with HIV-1. The phase 3 SALSA study evaluated efficacy and safety of switching to DTG/3TC compared with continuing various 3-/4-drug current antiretroviral regimens (CAR). METHODS: Adults with HIV-1 RNA <50 copies/mL and no previous virologic failure were randomized (1:1, stratified by baseline third agent class) to switch to once-daily fixed-dose combination DTG/3TC or continue CAR (primary endpoint: proportion of participants with HIV-1 RNA ≥50 copies/mL at Week 48; Snapshot, intention-to-treat-exposed population, 5% non-inferiority margin). RESULTS: Overall, 493 adults (39% women; 39% aged ≥50 years; 19% African American/African heritage; 14% Asian) were randomized to switch to DTG/3TC (n=246) or continue CAR (n=247). At Week 48, 1 (0.4%) participant in the DTG/3TC group and 3 (1.2%) in the CAR group had HIV-1 RNA ≥50 copies/mL (Snapshot), demonstrating non-inferiority (adjusted difference, -0.8%; 95% CI, -2.4%, 0.8%). Zero participants met confirmed virologic withdrawal criteria; therefore, no resistance testing was performed. Drug-related adverse events were more frequent with DTG/3TC (20%) than CAR (6%) through Week 48 but comparable post-Week 24 (5% vs 2%, respectively). Proximal tubular renal function and bone turnover biomarkers improved with DTG/3TC. Both groups had generally minimal changes in lipids and inflammatory biomarkers. CONCLUSIONS: Switching to DTG/3TC was non-inferior to continuing CAR for maintaining virologic suppression at Week 48 with no observed resistance, supporting the efficacy, good safety, and high barrier to resistance of DTG/3TC.