在成人人类免疫缺陷病毒 1（HIV-1）感染者中，转换为二药方案多替拉韦/拉米夫定与继续三药或四药方案维持病毒学抑制的疗效和安全性：来自 III 期非劣效性 SALSA 随机试验的第 48 周结果。
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): Week 48 Results From the Phase 3, Noninferiority SALSA Randomized Trial.
机构信息
Hospital Universitari Germans Trias i Pujol, Barcelona, Spain.
Universidade Federal da Bahia, Salvador, Brazil.
出版信息
Clin Infect Dis. 2023 Feb 18;76(4):720-729. doi: 10.1093/cid/ciac130.
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.
背景
在 TANGO 研究中，与继续使用基于替诺福韦艾拉酚胺的方案相比，转换为多替拉韦/拉米夫定（DTG/3TC）在治疗经验丰富的 HIV-1 成人中显示出长期非劣效疗效。这项 3 期 SALSA 研究评估了与继续使用各种 3/4 种药物的现有抗逆转录病毒方案（CAR）相比，转换为 DTG/3TC 的疗效和安全性。
方法
HIV-1 RNA<50 拷贝/ml 且无既往病毒学失败的成人随机分为（1:1，按基线时的第三种药物类别分层）接受每日一次固定剂量联合 DTG/3TC 或继续 CAR（主要终点：第 48 周时 HIV-1 RNA≥50 拷贝/ml 的参与者比例；Snapshot，意向治疗暴露人群，5%非劣效性边界）。
结果
共有 493 名成人（39%女性；39%年龄≥50 岁；19%非裔美国人/非洲裔；14%亚裔）被随机分配至转换为 DTG/3TC 组（n=246）或继续 CAR 组（n=247）。在第 48 周时，DTG/3TC 组有 1 名（0.4%）参与者和 CAR 组有 3 名（1.2%）参与者的 HIV-1 RNA≥50 拷贝/ml（Snapshot），显示非劣效性（校正差异，-0.8%；95%CI，-2.4%，.8%）。零名参与者符合确认的病毒学停药标准；因此，未进行耐药性检测。DTG/3TC 组药物相关不良事件的发生率（20%）高于 CAR 组（6%），直至第 48 周，但在第 24 周后相似（分别为 5%和 2%）。DTG/3TC 可改善近端肾小管肾功能和骨转换生物标志物。两组的脂质和炎症生物标志物均有轻微变化。
结论
在第 48 周时，与继续 CAR 相比，转换为 DTG/3TC 可维持病毒学抑制，且无耐药性观察结果，支持 DTG/3TC 的疗效、良好的安全性和高耐药屏障。
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