使用电子剂量监测评估的依从性与人类免疫缺陷病毒/艾滋病和耐多药结核病患者出现紧急抗逆转录病毒耐药和不良结局相关。
Adherence Measured Using Electronic Dose Monitoring is Associated with Emergent Antiretroviral Resistance and Poor Outcomes in People with Human Immunodeficiency Virus/AIDS and Multidrug-Resistant Tuberculosis.
机构信息
Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.
Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University Irving Medical Center, New York, New York, USA.
出版信息
Clin Infect Dis. 2022 Oct 29;75(9):1489-1496. doi: 10.1093/cid/ciac232.
BACKGROUND
Medication adherence is known to challenge treatment of human immunodeficiency virus (HIV)/AIDS and multidrug-resistant tuberculosis (MDR-TB). We hypothesized that adherence using electronic dose monitoring (EDM) would identify an antiretroviral therapy (ART) adherence threshold for emergent ART resistance and predict treatment outcomes in patients with MDR-TB and HIV on ART and bedaquiline-containing TB regimens.
METHODS
A prospective cohort of adults with MDR-TB and HIV on ART and initiating MDR-TB treatment with bedaquiline were enrolled at a public hospital in KwaZulu-Natal, South Africa (PRAXIS Study). Participants received separate EDM devices that measure adherence to bedaquiline and ART (nevirapine or lopinavir/ritonavir). Adherence was calculated cumulatively over 6 months. Participants were followed through completion of MDR-TB treatment. HIV genome sequencing was performed at baseline and 2 and 6 months on samples with HIV RNA ≥1000 copies/mL.
RESULTS
From November 2016 through February 2018, 198 persons with MDR-TB and HIV were enrolled and followed (median, 17.2 months; interquartile range, 12.2-19.6). Eleven percent had baseline ART resistance mutations, and 7.5% developed emergent ART resistance at 6 months. ART adherence was independently associated with ART resistance and mortality. Modeling identified a significant (P < .001), linear association between ART adherence and emergent resistance, suggesting a strong association without a specific threshold.
CONCLUSIONS
Our findings highlight the need for ART resistance testing, especially in patients with MDR-TB and HIV, which is currently not the standard of care in resource-limited settings. Despite short follow-up duration, reduced ART adherence was significantly associated with emergent resistance and increased mortality.
CLINICAL TRIALS REGISTRATION
NCT03162107.
背景
众所周知，药物依从性是治疗人类免疫缺陷病毒（HIV）/艾滋病和耐多药结核病（MDR-TB）的挑战。我们假设，电子剂量监测（EDM）的依从性将确定抗逆转录病毒治疗（ART）的依从性阈值，以发现ART 耐药，并预测正在接受 ART 治疗的 MDR-TB 和 HIV 患者以及接受包含贝达喹啉的结核病方案治疗的患者的治疗结局。
方法
在南非夸祖鲁-纳塔尔省的一家公立医院（PRAXIS 研究），对正在接受 ART 治疗且开始接受包含贝达喹啉的 MDR-TB 治疗的 MDR-TB 和 HIV 成人患者进行了前瞻性队列研究。参与者接受了单独的 EDM 设备，用于测量对贝达喹啉和 ART（奈韦拉平或洛匹那韦/利托那韦）的依从性。在 6 个月内累积计算依从性。参与者在 MDR-TB 治疗完成后接受随访。在基线以及 HIV RNA≥1000 拷贝/mL 的样本中，第 2 个月和第 6 个月时进行 HIV 基因组测序。
结果
从 2016 年 11 月至 2018 年 2 月，共纳入并随访了 198 名患有 MDR-TB 和 HIV 的患者（中位数为 17.2 个月；四分位距，12.2-19.6）。11%的患者基线时存在 ART 耐药突变，7.5%的患者在 6 个月时出现了新兴的 ART 耐药。ART 依从性与 ART 耐药和死亡率独立相关。模型确定了 ART 依从性与新兴耐药性之间存在显著（P<.001）、线性关联，表明存在强关联而没有特定的阈值。
结论
我们的研究结果强调了 ART 耐药检测的必要性，尤其是在 MDR-TB 和 HIV 患者中，这在资源有限的环境中目前不是标准治疗方法。尽管随访时间短，但降低的 ART 依从性与新兴耐药和死亡率增加显著相关。
临床试验注册
NCT03162107。
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