Carlos Silveira Machado António, Figueiredo Cristóvão, Teixeira Tiago, Azevedo Carlos, Fragoso Joana, Nunes Sofia, Coutinho Daniel, Malheiro Luís
Medicine, Faculty of Medicine - University of Porto, Porto, PRT.
Infectious Diseases, Vila Nova de Gaia/Espinho Hospital Centre, Vila Nova de Gaia, PRT.
Cureus. 2023 Jul 10;15(7):e41647. doi: 10.7759/cureus.41647. eCollection 2023 Jul.
Introduction Multiple risk factors, such as human immunodeficiency virus (HIV) infection and immunosuppressive therapies, increase the odds of latent tuberculosis infection (LTBI) reactivation and progression to active tuberculosis. A six-to-nine-month preventive treatment with isoniazid (INH) decreases the risk of LTBI reactivation, but its effectiveness can be limited by its long duration and adverse events (AEs), including liver toxicity. Due to comorbidities and polypharmacy, people living with HIV (PLHIV) may be at increased risk of INH-associated AEs. Our study aimed to assess the prevalence of AEs among patients receiving INH treatment for LTBI, to identify risk factors for their occurrence, and to evaluate whether PLHIV have higher odds of developing INH-associated AEs. Methods We conducted a single-center retrospective case-control study, including 130 outpatients with LTBI treated with INH between July 2019 and March 2022. Participants who developed AE (cases) were compared to controls, and a subgroup of PLHIV was compared to HIV-negative participants. Demographics, socioeconomic variables, comorbidities, and clinical variables were compared between study groups. Patient data were obtained from institutional electronic medical records, and outcomes were measured at regularly scheduled appointments. Results We included 130 participants, of which 54 were PLHIV. The PLHIV subgroup was significantly younger (p = 0.01) and demonstrated significantly higher prevalences of chronic liver disease, previous viral hepatitis, daily alcohol consumption, and intravenous drug use (IDU). One-third of the participants had an AE (45 cases, 34.6%), with liver toxicity being the most common (22.3%). Participants who developed AEs were significantly older (p = 0.030) and had a higher prevalence of economic hardship (p = 0.037), as well as higher scores of the Charlson comorbidity index (p = 0.002) than the controls. INH withdrawal occurred in 17 participants (13.1%) and was mainly associated with liver toxicity (p < 0.01) and gastrointestinal symptoms (p = 0.022). In the adjusted effect model, an age ≥ 65 years, economic hardship, and excessive alcohol consumption were significantly associated with higher odds of AEs, while HIV infection decreased the odds by 68.4% (p = 0.033). Conclusions In our study, INH-associated AEs were common, with liver toxicity being the most frequent. Older age, economic hardship, and excessive alcohol consumption increased the odds of INH-associated AEs, while PLHIV had lower odds of developing INH-associated AEs, even when adjusting for other variables in the multivariate analysis. Further studies should be conducted to assess if these results are replicable in a larger population and in different settings.
引言 多种风险因素，如人类免疫缺陷病毒（HIV）感染和免疫抑制疗法，会增加潜伏性结核感染（LTBI）重新激活并进展为活动性结核病的几率。使用异烟肼（INH）进行6至9个月的预防性治疗可降低LTBI重新激活的风险，但其有效性可能会受到疗程长和不良事件（AE）的限制，包括肝毒性。由于合并症和多种药物治疗，HIV感染者（PLHIV）发生INH相关不良事件的风险可能更高。我们的研究旨在评估接受INH治疗LTBI的患者中不良事件的发生率，确定其发生的风险因素，并评估PLHIV发生INH相关不良事件的几率是否更高。方法 我们进行了一项单中心回顾性病例对照研究，纳入了2019年7月至2022年3月期间接受INH治疗的130例LTBI门诊患者。将发生不良事件的参与者（病例）与对照组进行比较，并将PLHIV亚组与HIV阴性参与者进行比较。比较研究组之间的人口统计学、社会经济变量、合并症和临床变量。患者数据来自机构电子病历，并在定期预约时进行结果测量。结果 我们纳入了130名参与者，其中54名是PLHIV。PLHIV亚组明显更年轻（p = 0.01），并且慢性肝病、既往病毒性肝炎、每日饮酒和静脉吸毒（IDU）的患病率明显更高。三分之一的参与者发生了不良事件（45例，34.6%），其中肝毒性最为常见（22.3%）。发生不良事件的参与者比对照组明显年龄更大（p = 0.030），经济困难的患病率更高（p = 0.037），以及Charlson合并症指数得分更高（p = 0.002）。17名参与者（13.1%）停用了INH，主要与肝毒性（p < 0.01）和胃肠道症状（p = 0.022）有关。在调整后的效应模型中，年龄≥65岁、经济困难和过量饮酒与不良事件的几率显著相关，而HIV感染使几率降低了68.4%（p = 0.033）。结论 在我们的研究中，INH相关不良事件很常见，肝毒性最为频繁。年龄较大、经济困难和过量饮酒增加了INH相关不良事件的几率，而PLHIV发生INH相关不良事件的几率较低，即使在多变量分析中调整了其他变量也是如此。应进行进一步研究，以评估这些结果在更大人群和不同环境中是否可重复。
