电子剂量监测评估贝达喹啉依从性可预测耐多药结核病合并 HIV/AIDS 患者的临床结局。
Bedaquiline Adherence Measured by Electronic Dose Monitoring Predicts Clinical Outcomes in the Treatment of Patients With Multidrug-Resistant Tuberculosis and HIV/AIDS.
机构信息
Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University Medical Center, New York City, NY.
Department of Epidemiology, Columbia University Medical Center, New York City, NY.
出版信息
J Acquir Immune Defic Syndr. 2022 Jul 1;90(3):325-332. doi: 10.1097/QAI.0000000000002940.
BACKGROUND
Novel regimens have revolutionized multidrug-resistant tuberculosis (MDR-TB) treatment; however, medication adherence remains challenging and poorly characterized. We hypothesized that bedaquiline adherence, measured using electronic dose monitoring, would predict MDR-TB treatment outcomes.
SETTING
This is a prospective cohort study conducted in KwaZulu-Natal, South Africa.
METHODS
Adults with MDR-TB and HIV initiating bedaquiline and on antiretroviral therapy (ART) were eligible. Separate electronic dose monitoring devices measured bedaquiline and ART adherence through 6 months, calculated as observed versus expected doses. Whole-genome sequencing was performed to identify bedaquiline resistance-associated variants.
RESULTS
From November 2016 through February 2018, 199 participants with MDR-TB and HIV were enrolled and followed up through treatment completion (median 17.2 months interquartile range 12.2-19.6). The median bedaquiline adherence was higher than ART adherence (97 vs. 89%, P < 0.001) but correlated (r2 = 0.68, P < 0.001). High bedaquiline adherence (≥90%) compared with lower adherence was associated with improved end of treatment successful outcome (83.4% vs. 46.3%, P < 0.001), decreased mortality (11.0% vs. 29.6% P = 0.004), and improved retention in care through end of treatment (94.5% vs. 79.6% P = 0.002). Modeling identified a highly significant but linear association between bedaquiline adherence and outcome. On multivariable analysis, bedaquiline adherence was independently associated with mortality and outcome. Bedaquiline resistance-associated variants were seen in 12% (7/57) of sequenced isolates (7% baseline, 5% emergent) with only 28.6% experiencing successful treatment outcome.
CONCLUSIONS
Bedaquiline adherence through 6 months independently predicted end of MDR-TB treatment outcome, but a specific bedaquiline adherence threshold was not identified. Interventions to optimize bedaquiline adherence are urgently needed to improve MDR-TB HIV treatment outcomes.
背景
新的治疗方案彻底改变了耐多药结核病（MDR-TB）的治疗方式；然而，药物依从性仍然是一个挑战，并且了解甚少。我们假设，使用电子剂量监测来衡量的贝达喹啉依从性将预测 MDR-TB 治疗结果。
地点
这是在南非夸祖鲁-纳塔尔省进行的一项前瞻性队列研究。
方法
符合条件的参与者为开始使用贝达喹啉和抗逆转录病毒治疗（ART）的 MDR-TB 和 HIV 成人患者。通过电子剂量监测设备分别测量 6 个月内的贝达喹啉和 ART 依从性，计算方法是观察到的剂量与预期剂量的比值。对全基因组测序以确定贝达喹啉耐药相关变异。
结果
从 2016 年 11 月至 2018 年 2 月，共纳入 199 名患有 MDR-TB 和 HIV 的患者，并在治疗完成后进行随访（中位数为 17.2 个月，四分位距为 12.2-19.6 个月）。贝达喹啉的依从性中位数高于 ART 依从性（97%比 89%，P<0.001），但两者相关（r2=0.68，P<0.001）。与较低的依从性相比，高贝达喹啉依从性（≥90%）与治疗结束时的成功结局（83.4%比 46.3%，P<0.001）、死亡率降低（11.0%比 29.6%，P=0.004）和治疗结束时保持在治疗中有关（94.5%比 79.6%，P=0.002）。模型确定了贝达喹啉依从性与结局之间存在显著但线性的关联。在多变量分析中，贝达喹啉依从性与死亡率和结局独立相关。在测序的 57 个分离株中，发现了 12%（7/57）的贝达喹啉耐药相关变异（基线时 7%，新出现的 5%），只有 28.6%的患者治疗成功。
结论
6 个月内的贝达喹啉依从性独立预测 MDR-TB 治疗结束时的结局，但未确定具体的贝达喹啉依从性阈值。迫切需要优化贝达喹啉依从性的干预措施，以改善 MDR-TB 合并 HIV 治疗的结局。
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