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Switching to the 2-drug regimen of dolutegravir/lamivudine (DTG/3TC) fixed-dose combination (FDC) is non-inferior to continuing a 3-drug regimen through 24 weeks in a randomized clinical trial (SALSA)

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BACKGROUND: Long-term non-inferior efficacy of the 2-drug regimen (2DR) DTG/3TC compared with 3/4-drug regimens (3/4DRs) has been demonstrated in treatment-naive (DTG + TDF/FTC through 144 weeks) and treatment-experienced individuals with HIV-1 (TAF-based regimens through 96 weeks), with a good safety profile and a high barrier to resistance. We evaluated the efficacy and safety of switching to DTG/3TC fixed-dose combination (FDC) in adults with HIV-1 on any current antiretroviral regimen (CAR).
METHODS: SALSA is a randomized, controlled, open-label study. Participants with HIV-1 RNA <50 c/mL for >6 months on a 3/4DR without prior virologic failure or NRTI or DTG resistance-associated mutations were randomized 1:1 (stratified by baseline third agent class) to switch to DTG/3TC or continue CAR for 52 weeks. Primary endpoint was proportion of participants with plasma HIV-1 RNA '¥50 c/mL at Week 48 (FDA Snapshot algorithm, ITT-E population). Planned Week 24 interim analysis assessed non-inferiority with a 5% margin.
RESULTS: Overall, 493 participants were randomized (59% white; 39% women; 39% aged >50 years; 50%/40%/10% on NNRTI/INSTI/PI at baseline). DTG/3TC was non-inferior to continuing CAR at Week 24 using Snapshot virologic failure, and results were consistent with the Snapshot virologic success analysis (Table). No participants in either arm met confirmed virologic withdrawal criteria; therefore, no resistance testing was done. Overall safety outcomes were comparable between the DTG/3TC and CAR groups for frequency of any AEs (60% vs 60%), AEs leading to withdrawal (2% vs <1%), and serious AEs (1% vs 6%), respectively.

Table. Week 24 Study Outcome by Snapshot Analysis

n (%)
DTG/3TC
(N=246)
CAR
(N=247)


Adjusted difference (95% CI)
HIV-1 RNA '¥50 c/mLa
01 (<1)
'0.4% ('1.2%, 0.4%)
HIV-1 RNA <50 c/mL (virologic success)
234 (95)
237 (96)
'0.8% ('4.5%, 2.8%)
No virologic data
12 (5)
9 (4)
'
aEstimates and confidence intervals were based on a stratified analysis using Cochran-Mantel-Haenszel weights adjusting for baseline third agent class.

CONCLUSIONS: In SALSA, switching to DTG/3TC was non-inferior to continuing CAR in maintaining virologic suppression at Week 24, with a safety profile consistent with the DTG and 3TC labels. Through 24 weeks, DTG/3TC 2DR offers a switch option with fewer antiretroviral drugs compared with traditional 3DRs, without increased risk of virologic failure or resistance. The study is ongoing; the conference presentation will include lipid data and Week 48 results.