Postgraduate Program Clinical Research in Infectious Diseases, National Institute of Infectious Diseases Evandro Chagas, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
Clinical Research Laboratory on Mycobacteria, (LAPCLIN-TB), National Institute of Infectious Diseases Evandro Chagas, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
PLoS One. 2023 Feb 7;18(2):e0269765. doi: 10.1371/journal.pone.0269765. eCollection 2023.
Adverse drug reactions (ADR) challenge successful anti-tuberculosis treatment (ATT). The aim of this study was to evaluate the impact of ATT-associated ADR and related factors on ATT outcomes.
A prospective cohort study of persons with tuberculosis (TB) at a referral center in Rio de Janeiro, Brazil, from 2010 to 2016. Baseline information: race, sex, schooling, economic status, tobacco, drugs and alcohol abuse, HIV-infection status and comorbidities were captured during TB screening and diagnosis. Laboratory exams were performed to confirm TB diagnosis and monitor ADRs, favorable (cure and treatment completion) and unfavorable (death, loss to follow up and failure) outcomes were prospectively captured. The Kaplan-Meier curve was used to estimate the probability of ADR-free time. A logistic regression analysis (backward elimination) was performed to identify independent associations with unfavorable outcomes.
550 patients were enrolled, 35.1% were people living with HIV (PLHIV) and ADR occurred in 78.6% of all participants. Smoking (OR: 2.32; 95% CI:1.34-3.99) and illicit-drug use (OR:2.02; 95% CI:1.15-3.55) were independent risk factors for unfavorable outcomes. In PLHIV, alcohol abuse and previous ART use were associated with unfavorable outcomes. In contrast, ADR increased the odds of favorable outcomes in the overall population. PLHIV more frequently experienced grade 3/4-ADR (18.36%), especially "liver and biliary system disorders". Lower CD4 counts (<100 cells/uL) were associated with hepatotoxicity (p = 0.03). ART-naïve participants presented a higher incidence of ADR in comparison with ART-experienced patients.
Substance use was associated with unfavorable outcomes, highlighting the need for better strategies to reduce this habit. In contrast, ADRs were associated with favorable outcomes. Attention to the occurrence of ADR in PLHIV is essential, especially regarding hepatotoxicity in those with high immunosuppression.
药物不良反应（ADR）对结核病治疗（ATT）的成功产生挑战。本研究旨在评估 ATT 相关 ADR 及其相关因素对 ATT 结局的影响。
这是一项 2010 年至 2016 年在巴西里约热内卢转诊中心进行的结核患者前瞻性队列研究。基线信息：种族、性别、受教育程度、经济状况、烟草、药物和酒精滥用、HIV 感染状况和合并症在结核病筛查和诊断期间进行采集。进行实验室检查以确认结核病诊断并监测 ADR，前瞻性采集有利（治愈和治疗完成）和不利（死亡、失访和失败）结局。使用 Kaplan-Meier 曲线估计无 ADR 时间的概率。采用逻辑回归分析（向后消除法）确定与不利结局相关的独立因素。
共纳入 550 例患者，35.1%为 HIV 感染者（PLHIV），所有参与者中有 78.6%发生 ADR。吸烟（OR：2.32；95%CI：1.34-3.99）和非法药物使用（OR：2.02；95%CI：1.15-3.55）是不利结局的独立危险因素。在 PLHIV 中，酒精滥用和既往 ART 使用与不利结局相关。相反，ADR 增加了总体人群中有利结局的几率。PLHIV 更常发生 3/4 级 ADR（18.36%），尤其是“肝脏和胆道系统疾病”。较低的 CD4 计数（<100 个细胞/μL）与肝毒性相关（p=0.03）。与 ART 经验丰富的患者相比，ART 初治患者发生 ADR 的发生率更高。
物质使用与不利结局相关，这突出表明需要采取更好的策略来减少这种习惯。相反，ADR 与有利结局相关。需要注意 PLHIV 中 ADR 的发生，特别是对于高免疫抑制患者的肝毒性。
