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Background Drug resistance testing aids in appropriate antiretroviral therapy selection to improve treatment success but may not be readily available. We evaluated the impact of switching to dolutegravir/lamivudine (DTG/3TC) using pooled data from the TANGO and SALSA trials in adults who were virologically suppressed with or without historical resistance results at screening. Methods Adults who were virologically suppressed (HIV-1 RNA <50 copies/mL for >6 months) with no prior virologic failure were randomized to switch to DTG/3TC (TANGO, n = 369; SALSA, n = 246) or continue their current antiretroviral regimen (CAR; TANGO, n = 372; SALSA, n = 247). Week 48 HIV-1 RNA ≥50 and <50 copies/mL (Snapshot algorithm, Food and Drug Administration; intention-to-treat exposed), CD4+ cell count, and safety were analyzed by availability of historical resistance results. Results Overall, 294 of 615 (48%) participants in the DTG/3TC group and 277 of 619 (45%) participants in the CAR group had no historical resistance results at screening. At week 48, proportions with Snapshot HIV-1 RNA ≥50 copies/mL were low (≤1.1%) and similar across treatment groups and by historical resistance results availability. High proportions (91%–95%) maintained virologic suppression through week 48, regardless of results availability. Across both subgroups of results availability, greater increases in CD4+ cell count from baseline to week 48 occurred with DTG/3TC vs CAR. No participants taking DTG/3TC had confirmed virologic withdrawal, regardless of historical resistance results availability. One participant undergoing CAR without historical resistance results had confirmed virologic withdrawal; no resistance was detected. Overall, DTG/3TC was well tolerated; few adverse events led to withdrawal. Conclusions Findings support DTG/3TC as a robust switch option for adults who are virologically suppressed with HIV-1 and no prior virologic failure, regardless of historical resistance results availability. Clinical trial registration TANGO: NCT03446573, https://clinicaltrials.gov/study/NCT03446573. SALSA: NCT04021290, https://clinicaltrials.gov/study/NCT04021290 [ABSTRACT FROM AUTHOR]

배경 The primary analysis of the STAT study demonstrated the feasibility, efficacy, and safety of using DTG/3TC as a first-line regimen in a test-and-treat setting through 24 weeks, with therapy adjustments for baseline resistance or hepatitis B virus (HBV) co-infection. Here we present secondary analyses through Week 48 of virologic outcomes in participants by baseline viral load (VL). 방법 STAT is a single-arm study of treatment-naive adults with HIV-1 infection who initiated DTG/3TC ≤14 days after HIV-1 diagnosis without availability of screening/baseline laboratory results. If baseline testing indicated DTG or 3TC resistance, HBV co-infection, or creatinine clearance <30 mL/min/1.73 m 2, then antiretroviral therapy (ART) was potentially adjusted and participants remained on study. Efficacy analyses included proportion of participants with HIV-1 RNA <50 c/mL regardless of ART regimen at Week 48, among all participants (ITT-E missing = failure analysis) and among participants with available HIV-1 RNA data at Week 48 (observed analysis). 결과 Of 131 enrolled, DTG/3TC treatment was adjusted in 10 participants, and of those with available data (n=7), all (100%) achieved HIV-1 RNA <50 c/mL at Week 48. At Week 48, 82% (107/131) of all participants (Figure 1) and 97% (107/110) of those with available data (Figure 2) achieved HIV-1 RNA <50 c/mL. Of participants with baseline VL ≥500,000 c/mL, 89% (17/19) achieved HIV-1 RNA <50 c/mL at Week 48; the remaining 2 withdrew from study. Of participants with baseline VL ≥1,000,000 c/mL, 90% (9/10) achieved HIV-1 RNA <50 c/mL at Week 48 (Table); the remaining participant withdrew consent. Of the 17 participants with baseline VL ≥500,000 c/mL with available data through Week 48, 76% (13/17) achieved virologic suppression by Week 24. One participant with baseline VL ≥500,000 c/mL switched from DTG/3TC before the Week 48 assessment. Of the 9 participants with baseline VL ≥1,000,000 c/mL with available data through Week 48, most participants (8/9; 89%) were suppressed by Week 24. 결론 These data provide evidence for the efficacy and feasibility of using DTG/3TC as a first-line regimen in a test-and-treat setting, including among participants with very high baseline VL. Data included in this abstract have previously been presented in full at IDWeek 2021; September 29-October 3, 2021; Virtual; Slides 75. [ABSTRACT FROM AUTHOR]

Background: Dolutegravir/Lamivudine (DTG/3TC) has durable efficacy and a high barrier to resistance, supporting its inclusion in international guidelines as a recommended INSTI-based regimen. We present pooled efficacy and safety outcomes among virologically suppressed adults switching to DTG/3TC by baseline regimen. Methods: This analysis includes 48-week data from the phase 3 TANGO and SALSA trials of adults with HIV-1 RNA <50 c/mL randomized to switch to once-daily DTG/3TC fixed-dose combination or continue current antiretroviral regimen (CAR). Primary and key secondary endpoints were proportions with HIV-1 RNA ≥50 and <50 c/mL at Week 48, respectively (Snapshot, intention-to-treat exposed). Results: Among 1234 participants, the most commonly used baseline third agent class and NRTI backbone were INSTIs (63%) and TAF/FTC (74%), respectively. Overall, at Week 48, few participants had HIV-1 RNA ≥50 c/mL (adjusted difference, −0.5; 95% CI, −1.3, 0.4); results were consistent across baseline regimen subgroups. High proportions of participants maintained HIV-1 RNA <50 c/mL in the DTG/3TC and CAR groups across baseline regimen use (Table). No DTG/3TC participants had confirmed virologic withdrawal (CVW); 1 CAR participant had CVW (no resistance detected). In the overall analysis, proportions of any adverse events (AEs) and grade 2-5 AEs were similar between treatment groups, with few AEs leading to withdrawal or serious AEs; drug-related AEs were more frequent in the DTG/3TC group, as expected in stable switch studies. Similar results were observed by baseline regimen use. Conclusion: DTG/3TC maintained high proportions of virologic suppression, had a high barrier to resistance, and demonstrated a good safety and tolerability profile 1 year after switch regardless of prior 3-/4-drug regimen use, supporting this 2-drug regimen as a robust, well-tolerated switch option with fewer antiretrovirals. [ABSTRACT FROM AUTHOR]