Teira Ramón, Diaz-Cuervo Helena, Aragão Filipa, Marguet Sophie, de la Fuente Belén, Muñoz Maria Jose, Abdulghani Nadia, Ribera Esteban, Domingo Pere, Deig Elisabeth, Peraire Joaquim, Roca Bernardino, Montero Marta, Galindo Maria José, Romero Alberto, Espinosa Nuria, Lozano Fernando, Merino María Dolores, Martínez Elisa, Geijo Paloma, Estrada Vicente, García Josefina, Sepúlveda M Antonia, Berenguer Juan
Hospital de Sierrallana, Torrelavega, Spain.
Gilead Sciences, Medical Affairs, Stockley Park HEOR, Spain.
PLoS One. 2021 Apr 8;16(4):e0249515. doi: 10.1371/journal.pone.0249515. eCollection 2021.
Since 1996, the standard of care (SOC) therapy for HIV treatment has consisted of a backbone of two nucleoside analogue reverse transcriptase inhibitors (NRTI) paired with a third agent. Use of two-drug combinations (2DC) has been considered for selected patients to avoid toxicities associated with the use of NRTIs. This study aimed to compare the real-world outcomes of integrase strand transfer inhibitor (INSTI)-containing triple therapy (TT) to dolutegravir- (DTG) and/or boosted protease inhibitor (bPI)-based 2DC in a large Spanish cohort of HIV patients.
A retrospective analysis was performed using data from the VACH cohort, a prospective multicentre Spanish cohort of adult HIV patients. All treatment experienced patients initiating a TT of an INSTI combined with two NRTIs or a 2DC-containing DTG and/or a bPI between 01/01/2012 and 01/06/2017 were included. The unit of analysis was patient-regimens. The overall sample analysis was complemented with two sub-analyses. The first sub-analysis focused on patients treated with a backbone plus DTG compared to those treated with DTG+ one other antiretroviral. The second sub-analysis focused on patients with HIV RNA<50 copies/mL at baseline, irrespective of the regimen used. The following endpoints were assessed: time to discontinuation for any reason, time to switch due to virologic failure, and time to switch due to toxicity (reasons for discontinuation according to clinician report in the database). Time-to-event analyses were conducted using Kaplan-Meier survival curves and Cox regression models.
Overall 7,481 patients were included in the analysis, contributing to 9,243 patient-regimens. Patient characteristics at baseline differed among groups, with the 2DC group being significantly older and having a higher proportion of women, a longer time on ART and a higher number of previous virologic failures. Median (95% Confidence Interval [C.I.]) time to switch was 2.5 years (2.3, 2.7) in 2DC group versus 2.9 years (2.7, 3.0) in TT. Adjusted hazard ratios (95% C.I.) for discontinuation due to any reason, virologic failure and toxicity in the 2DC vs TT group were 1.29 (1.15; 1.44), 2.06 (1.54; 2.77) and 1.18 (0.94; 1.48), respectively. Results were consistent in the two sub-analyses.
In this analysis, time to discontinuation and probability of remaining free of virologic failure were significantly higher in patients on INSTI-based TT compared to DTG- and/or bPI-containing 2DC, with no differences in toxicity.
自1996年以来，HIV治疗的标准治疗（SOC）方案一直是由两种核苷类逆转录酶抑制剂（NRTI）组成的主干方案与第三种药物联合使用。对于部分患者，考虑使用两药联合方案（2DC）以避免与使用NRTI相关的毒性。本研究旨在比较在西班牙一个大型HIV患者队列中，含整合酶链转移抑制剂（INSTI）的三联疗法（TT）与基于多替拉韦（DTG）和/或增强型蛋白酶抑制剂（bPI）的2DC的实际治疗效果。
使用来自VACH队列的数据进行回顾性分析，VACH队列是西班牙一个针对成年HIV患者的前瞻性多中心队列。纳入所有在2012年1月1日至2017年6月1日期间开始接受INSTI联合两种NRTI的TT治疗或含DTG和/或bPI的2DC治疗的有治疗经验的患者。分析单位是患者-治疗方案。总体样本分析辅以两项亚分析。第一项亚分析聚焦于接受主干方案加DTG治疗的患者与接受DTG加另一种抗逆转录病毒药物治疗的患者。第二项亚分析聚焦于基线时HIV RNA<50拷贝/mL的患者，无论使用何种治疗方案。评估了以下终点：因任何原因停药的时间、因病毒学失败换药的时间以及因毒性换药的时间（根据数据库中临床医生报告的停药原因）。使用Kaplan-Meier生存曲线和Cox回归模型进行事件发生时间分析。
总体分析纳入了7481例患者，共9243个患者-治疗方案。各组基线时的患者特征存在差异，2DC组患者年龄显著更大，女性比例更高，接受抗逆转录病毒治疗的时间更长，既往病毒学失败次数更多。2DC组换药的中位时间（95%置信区间[C.I.]）为2.5年（2.3，2.7），而TT组为2.9年（2.7，3.0）。2DC组与TT组因任何原因停药、因病毒学失败停药和因毒性停药的调整后风险比（95% C.I.）分别为1.29（1.15；1.44）、2.06（1.54；2.77）和1.18（0.94；1.48）。两项亚分析的结果一致。
在本分析中，与含DTG和/或bPI 的2DC相比，接受基于INSTI的TT治疗的患者停药时间和无病毒学失败的概率显著更高，毒性方面无差异。
