Wang Ruolan, Underwood Mark, Llibre Josep M, Bernal Morell Enrique, Brinson Cynthia, Sanz Moreno José, Scholten Stefan, Moore Richard, Saggu Parminder, Oyee James, Moodley Riya, Wynne Brian, Kisare Michelle, Jones Bryn, Ait-Khaled Mounir
ViiV Healthcare, Durham, North Carolina, USA.
Infectious Diseases Division and Fight Infections Foundation, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain.
Open Forum Infect Dis. 2023 Dec 9;11(1):ofad626. doi: 10.1093/ofid/ofad626. eCollection 2024 Jan.
We compared proportions of participants with target detected, target not detected (TND), and elevated viral load (VL) and assessed baseline variables associated with week 144 inflammatory biomarker levels between dolutegravir-lamivudine (DTG/3TC) and tenofovir alafenamide-based regimens (TBRs) in the TANGO study (post hoc).
TANGO is an open-label, multicenter, phase 3 study that randomized adults with VL <50 copies/mL to switch to once-daily fixed-dose DTG/3TC or continue TBR. At baseline and each study visit, the VL was measured. Elevated VL event frequencies were assessed, including "blips." Interleukin 6, D-dimer, high-sensitivity C-reactive protein, soluble CD14, and soluble CD163 were measured at baseline and at week 144. Log-transformed week 144 biomarker levels were compared between treatment groups using an analysis of covariance model adjusting for baseline variables.
High, comparable proportions of participants had VL <40 copies/mL and TND at week 144 (DTG/3TC, 279 of 369 [76%]; TBR, 267 of 372 [72%], intention-to-treat exposed Snapshot analysis; adjusted difference, 3.9% [95% confidence interval, -2.5% to 10.2%]), with similar TND proportions at all postbaseline visits (123 of 369 [33%] vs 101 of 372 [27%], respectively). Similar proportions of DTG/3TC participants had ≥1 postbaseline VL ≥50 copies/mL (28 of 369 [8%] vs 42 of 372 [11%] for TBR), primarily blips (18 of 369 [5%] and 26 of 372 [7%], respectively). Week 144 inflammatory biomarker levels were low and comparable between groups and associated with multiple demographic and baseline characteristics, including baseline biomarker levels, indicating a multifactorial inflammatory response.
Week 144 biomarker levels were low and generally comparable between treatment groups, reflecting similar, robust, and durable viral suppression observed using the stringent TND end point. ClinicalTrials.gov, NCT03446573.
在TANGO研究（事后分析）中，我们比较了接受多替拉韦-拉米夫定（DTG/3TC）和替诺福韦艾拉酚胺方案（TBR）治疗的参与者中检测到目标病毒载量、未检测到目标病毒载量（TND）以及病毒载量升高（VL）的比例，并评估了与第144周炎症生物标志物水平相关的基线变量。
TANGO是一项开放标签、多中心、3期研究，将病毒载量<50拷贝/mL的成年人随机分组，分别改为每日一次固定剂量的DTG/3TC或继续使用TBR方案。在基线和每次研究访视时测量病毒载量。评估病毒载量升高事件的频率，包括“病毒载量波动”。在基线和第144周时测量白细胞介素6、D-二聚体、高敏C反应蛋白、可溶性CD14和可溶性CD163。使用协方差分析模型对基线变量进行调整，比较治疗组之间第144周经对数转换的生物标志物水平。
在第144周时，接受DTG/3TC和TBR治疗的参与者中病毒载量<40拷贝/mL和TND的比例较高且相当（DTG/3TC组，369例中的279例[76%]；TBR组，372例中的267例[72%]，意向性分析；校正差异为3.9%[95%置信区间，-2.5%至10.2%]），在所有基线后访视中TND比例相似（分别为369例中的123例[33%]和372例中的101例[27%]）。DTG/3TC组和TBR组中病毒载量≥50拷贝/mL的基线后参与者比例相似（分别为369例中的28例[8%]和372例中的42例[11%]），主要为病毒载量波动（分别为369例中的18例[5%]和372例中的26例[7%]）。第144周时炎症生物标志物水平较低，且两组之间相当，并与多种人口统计学和基线特征相关，包括基线生物标志物水平，表明存在多因素炎症反应。
第144周时生物标志物水平较低，且治疗组之间总体相当，这反映了使用严格的TND终点观察到的相似、强劲且持久的病毒抑制效果。 临床试验注册号：NCT03446573 。
