Matono Takashi, Nishijima Takeshi, Teruya Katsuji, Morino Eriko, Takasaki Jin, Gatanaga Hiroyuki, Kikuchi Yoshimi, Kaku Mitsuo, Oka Shinichi
1 AIDS Clinical Center, National Center for Global Health and Medicine , Tokyo, Japan .
2 Department of Infection Control and Laboratory Diagnostics, Internal Medicine, Tohoku University Graduate School of Medicine , Sendai, Japan .
AIDS Patient Care STDS. 2017 Nov;31(11):455-462. doi: 10.1089/apc.2017.0116.
Little information exists on the frequency, severity, and timing of first-line anti-tuberculosis drug-related adverse events (TB-AEs) in HIV-tuberculosis coinfected (HIV-TB) patients in the antiretroviral therapy (ART) era. This matched-cohort study included HIV-TB patients as cases and HIV-uninfected tuberculosis (non-HIV-TB) patients as controls. Tuberculosis was culture-confirmed in both groups. Cases were matched to controls in a 1:4 ratio on age, sex, and year of diagnosis. TB-AEs were defined as Grade 2 or higher requiring drug discontinuation/regimen change. From 2003 to 2015, 94 cases and 376 controls were analyzed (95% men, 98% Asians). Standard four-drug combination therapy was initiated in 91% of cases and 89% of controls (p = 0.45). Cases had a higher frequency of TB-AE [51% (48/94) vs. 10% (39/376), p < 0.001]. Their major TB-AEs were fever (19%), rash (11%), and neutropenia (11%). TB-AEs were more severe in cases [Grade 3 or higher: cases (71%, 34/48) vs. controls (49%, 19/39), p < 0.001]. The time from treatment initiation to TB-AE was shorter in cases [median 18 (interquartile range 12-28) vs. 27 (15-57) days, p = 0.027], and 73% of TB-AEs in cases occurred within 4 weeks of starting anti-tuberculosis treatment. HIV infection was an independent risk factor for TB-AEs in the multivariate Cox analysis [adjusted HR (aHR): 6.96; 95% confidence interval: 3.93-12.3]. TB-AEs occurred more frequently in HIV-TB than in non-HIV-TB patients, and were more severe. The majority of TB-AEs occurred within 4 weeks of initiating anti-tuberculosis treatment. Because TB-AEs may delay ART initiation, careful monitoring during this period is warranted in coinfected patients.
在抗逆转录病毒治疗（ART）时代，关于合并感染人类免疫缺陷病毒（HIV）和结核病（HIV-TB）患者一线抗结核药物相关不良事件（TB-AEs）的发生频率、严重程度和发生时间的信息较少。这项配对队列研究纳入HIV-TB患者作为病例组，未感染HIV的结核病患者（非HIV-TB）作为对照组。两组的结核病均经培养确诊。病例组与对照组按年龄、性别和诊断年份以1:4的比例进行配对。TB-AEs被定义为2级或更高等级且需要停药/更改治疗方案的情况。2003年至2015年，共分析了94例病例和376例对照（95%为男性，98%为亚洲人）。91%的病例组和89%的对照组开始使用标准四联抗结核治疗（p = 0.45）。病例组的TB-AE发生频率更高[51%（48/94） vs. 10%（39/376），p < 0.001]。其主要的TB-AEs为发热（19%）、皮疹（11%）和中性粒细胞减少（11%）。病例组的TB-AEs更严重[3级或更高等级：病例组（71%，34/48） vs. 对照组（49%，19/39），p < 0.001]。病例组从开始治疗到发生TB-AE的时间更短[中位数18（四分位间距12 - 28）天 vs. 27（15 - 谱57）天，p = 0.027]，病例组73%的TB-AEs发生在开始抗结核治疗的4周内。在多变量Cox分析中，HIV感染是TB-AEs的独立危险因素[调整后风险比（aHR）：6.96；95%置信区间：3.93 - 12.3]。HIV-TB患者中TB-AEs的发生频率高于非HIV-TB患者，且更严重。大多数TB-AEs发生在开始抗结核治疗的4周内。由于TB-AEs可能会延迟ART的启动，因此在此期间对合并感染患者进行仔细监测是必要的。
