TY - JOUR
T1 - Efficacy and Safety of Switching to the 2-Drug Regimen Dolutegravir/Lamivudine Versus Continuing a 3- or 4-Drug Regimen for Maintaining Virologic Suppression in Adults Living With Human Immunodeficiency Virus 1 (HIV-1)
T2 - Week 48 Results From the Phase 3, Noninferiority SALSA Randomized Trial
AU - Llibre, Josep M.
AU - Brites, Carlos
AU - Cheng, Chien Yu
AU - Osiyemi, Olayemi
AU - Galera, Carlos
AU - Hocqueloux, Laurent
AU - Maggiolo, Franco
AU - Degen, Olaf
AU - Taylor, Stephen
AU - Blair, Elizabeth
AU - Man, Choy
AU - Wynne, Brian
AU - Oyee, James
AU - Underwood, Mark
AU - Curtis, Lloyd
AU - Bontempo, Gilda
AU - Van Wyk, Jean
N1 - Publisher Copyright:
© 2022 The Author(s). Published by Oxford University Press for the Infectious Diseases Society of America.
PY - 2023/2/15
Y1 - 2023/2/15
N2 - Background: In TANGO, switching to dolutegravir/lamivudine (DTG/3TC) demonstrated long-term noninferior 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 (CARs). 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% noninferiority 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 noninferiority (adjusted difference, -0.8%; 95% CI, -2.4%,. 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 noninferior 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. Clinical Trials Registration: www.clinicaltrials.gov, NCT04021290.
AB - Background: In TANGO, switching to dolutegravir/lamivudine (DTG/3TC) demonstrated long-term noninferior 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 (CARs). 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% noninferiority 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 noninferiority (adjusted difference, -0.8%; 95% CI, -2.4%,. 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 noninferior 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. Clinical Trials Registration: www.clinicaltrials.gov, NCT04021290.
KW - 2-drug regimen
KW - dolutegravir/lamivudine
KW - integrase strand transfer inhibitor
KW - treatment-experienced
KW - virologic suppression
UR - http://www.scopus.com/inward/record.url?scp=85148678697&partnerID=8YFLogxK
U2 - 10.1093/cid/ciac130
DO - 10.1093/cid/ciac130
M3 - Article
C2 - 35235656
AN - SCOPUS:85148678697
SN - 1058-4838
VL - 76
SP - 720
EP - 729
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 4
ER -
