多替拉韦/拉米夫定在筛查时有或无既往耐药结果的HIV-1感染者中的疗效和安全性结局：48周汇总分析
Dolutegravir/Lamivudine Efficacy and Safety Outcomes in People With HIV-1 With or Without Historical Resistance Results at Screening: 48-Week Pooled Analysis.
作者信息
Scholten Stefan, Cahn Pedro, Portilla Joaquín, Bisshop Fiona, Hodder Sally, Ruane Peter, Kaplan Richard, Wynne Brian R, Man Choy Y, Grove Richard, Wang Ruolan, Jones Bryn, Ait-Khaled Mounir, Kisare Michelle, Okoli Chinyere
机构信息
Praxis Hohenstaufenring, Cologne, Germany.
Fundación Huésped, Buenos Aires, Argentina.
出版信息
Open Forum Infect Dis. 2024 Jul 1;11(7):ofae365. doi: 10.1093/ofid/ofae365. eCollection 2024 Jul.
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.
背景
耐药性检测有助于选择合适的抗逆转录病毒疗法以提高治疗成功率，但可能无法随时获得。我们使用TANGO和SALSA试验的汇总数据，评估了在筛查时病毒学得到抑制且有或无既往耐药结果的成人中换用多替拉韦/拉米夫定（DTG/3TC）的影响。
方法
病毒学得到抑制（HIV-1 RNA<50拷贝/mL超过6个月）且无既往病毒学失败史的成人被随机分为换用DTG/3TC组（TANGO组，n = 369；SALSA组，n = 246）或继续其当前抗逆转录病毒方案（CAR组；TANGO组，n = 372；SALSA组，n = 247）。根据既往耐药结果的可获得情况，分析第48周时HIV-1 RNA≥50和<50拷贝/mL（美国食品药品监督管理局的快照算法；意向性分析）、CD4+细胞计数及安全性。
结果
总体而言，DTG/3TC组615名参与者中有294名（48%）、CAR组619名参与者中有277名（45%）在筛查时无既往耐药结果。在第48周时，快照HIV-1 RNA≥50拷贝/mL的比例较低（≤1.1%），在各治疗组间及根据既往耐药结果的可获得情况来看均相似。无论结果是否可获得，高比例（91%-95%）的参与者在第48周时维持了病毒学抑制。在结果可获得情况的两个亚组中，与CAR组相比，DTG/3TC组从基线到第48周CD4+细胞计数的增加幅度更大。无论既往耐药结果是否可获得，服用DTG/3TC的参与者均未出现确诊的病毒学治疗中断。一名在无既往耐药结果情况下接受CAR治疗的参与者出现确诊的病毒学治疗中断；未检测到耐药。总体而言，DTG/3TC耐受性良好；很少有不良事件导致治疗中断。
结论
研究结果支持DTG/3TC作为HIV-1病毒学得到抑制且无既往病毒学失败史的成人的可靠换药选择，无论既往耐药结果是否可获得。
临床试验注册
TANGO：NCT03446573，https://clinicaltrials.gov/study/NCT03446573。SALSA：NCT04021290，https://clinicaltrials.gov/study/NCT04021290。
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