Sekaggya-Wiltshire C, von Braun A, Scherrer A U, Manabe Y C, Buzibye A, Muller D, Ledergerber B, Gutteck U, Corti N, Kambugu A, Byakika-Kibwika P, Lamorde M, Castelnuovo B, Fehr J, Kamya M R
Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda.
Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of Zurich, Zurich, Switzerland.
J Antimicrob Chemother. 2017 Apr 1;72(4):1172-1177. doi: 10.1093/jac/dkw534.
Toxicities due to anti-TB treatment frequently occur among TB/HIV-coinfected patients.
To determine the association between anti-TB drug concentrations and the occurrence of hepatotoxicity and peripheral neuropathy among TB/HIV-coinfected patients.
TB/HIV-coinfected patients were started on standard dose anti-TB treatment according to WHO guidelines. Anti-TB drug concentrations were measured using HPLC 1, 2 and 4 h after drug intake at 2, 8 and 24 weeks following initiation of TB treatment. Participants were assessed for hepatotoxicity using Division of AIDS toxicity tables and for peripheral neuropathy using clinical assessment of tendon reflexes, vibration sensation or symptoms. Cox regression was used to determine the association between toxicities and drug concentrations.
Of the 268 patients enrolled, 58% were male with a median age of 34 years. Participants with no hepatotoxicity or mild, moderate and severe hepatotoxicity had a median C max of 6.57 (IQR 4.83-9.41) μg/mL, 7.39 (IQR 5.10-10.20) μg/mL, 7.00 (IQR 6.05-10.95) μg/mL and 3.86 (IQR 2.81-14.24) μg/mL, respectively. There was no difference in the median C max of rifampicin among those who had hepatotoxicity and those who did not ( P = 0.322). There was no difference in the isoniazid median C max among those who had peripheral neuropathy 2.34 (1.52-3.23) μg/mL and those who did not 2.21 (1.45-3.11) μg/mL ( P = 0.49).
There was no association between rifampicin concentrations and hepatotoxicity or isoniazid concentrations and peripheral neuropathy among TB/HIV-coinfected patients.
抗结核治疗引起的毒性反应在结核病/艾滋病病毒合并感染患者中经常发生。
确定结核病/艾滋病病毒合并感染患者中抗结核药物浓度与肝毒性和周围神经病变发生之间的关联。
结核病/艾滋病病毒合并感染患者按照世界卫生组织指南开始接受标准剂量的抗结核治疗。在开始抗结核治疗后的第2、8和24周,于服药后1、2和4小时使用高效液相色谱法测定抗结核药物浓度。使用艾滋病毒性分类表评估参与者的肝毒性,并通过对腱反射、振动觉或症状的临床评估来评估周围神经病变。采用Cox回归分析确定毒性反应与药物浓度之间的关联。
在纳入的268例患者中,58%为男性,中位年龄为34岁。无肝毒性、轻度、中度和重度肝毒性的参与者的Cmax中位数分别为6.57(四分位间距4.83 - 9.41)μg/mL、7.39(四分位间距5.10 - 10.20)μg/mL、7.00(四分位间距6.05 - 10.95)μg/mL和3.86(四分位间距2.81 - 14.24)μg/mL。有肝毒性和无肝毒性者的利福平Cmax中位数无差异(P = 0.322)。有周围神经病变者的异烟肼Cmax中位数为2.34(1.52 - 3.23)μg/mL,无周围神经病变者为2.21(1.45 - 3.11)μg/mL,两者无差异(P = 0.49)。
结核病/艾滋病病毒合并感染患者中,利福平浓度与肝毒性或异烟肼浓度与周围神经病变之间无关联。