Background The relationship between concentrations of antituberculosis drugs, sputum culture conversion, and treatment outcome remains unclear. We sought to determine the association between antituberculosis drug concentrations and sputum conversion among patients coinfected with tuberculosis and human immunodeficiency virus (HIV) and receiving first-line antituberculosis drugs. Methods We enrolled HIV-infected Ugandans with pulmonary tuberculosis. Estimation of first-line antituberculosis drug concentrations was performed 1, 2, and 4 hours after drug intake at 2, 8, and 24 weeks of tuberculosis treatment. Serial sputum cultures were performed at each visit. Time-to-event analysis was used to determine factors associated with sputum culture conversion. Results We enrolled 268 HIV-infected patients. Patients with low isoniazid and rifampicin concentrations were less likely to have sputum culture conversion before the end of tuberculosis treatment (hazard ratio, 0.54; 95% confidence interval, .37-.77; P = .001) or by the end of follow-up (0.61; .44-.85; P = .003). Patients in the highest quartile for area under the rifampicin and isoniazid concentration-time curves for were twice as likely to experience sputum conversion than those in the lowest quartile. Rifampicin and isoniazid concentrations below the thresholds and weight <55 kg were both risk factors for unfavorable tuberculosis treatment outcomes. Only 4.4% of the participants had treatment failure. Conclusion Although low antituberculosis drug concentrations did not translate to a high proportion of patients with treatment failure, the association between low concentrations of rifampicin and isoniazid and delayed culture conversion may have implications for tuberculosis transmission. Clinical Trials Registration: NCT01782950.

中文翻译：

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低异烟肼和利福平浓度的结核病-人类免疫缺陷病毒合并感染患者的痰培养转化延迟。


背景 抗结核药物浓度、痰培养转化率和治疗结果之间的关系仍不清楚。我们试图确定同时感染结核病和人类免疫缺陷病毒（HIV）并接受一线抗结核药物的患者的抗结核药物浓度与痰液转化之间的关系。方法 我们招募了感染艾滋病毒并患有肺结核的乌干达人。在结核病治疗第 2、8 和 24 周时，在服药后 1、2 和 4 小时进行一线抗结核药物浓度的估计。每次就诊时均进行系列痰培养。使用事件时间分析来确定与痰培养转化相关的因素。结果 我们招募了 268 名 HIV 感染者。异烟肼和利福平浓度较低的患者在结核病治疗结束前（风险比，0.54；95% 置信区间，0.37-0.77；P = 0.001）或随访结束时出现痰培养转化的可能性较小。上升（0.61；.44-.85；P = .003）。利福平和异烟肼浓度-时间曲线下面积最高四分位数的患者出现痰转化的可能性是最低四分位数患者的两倍。利福平和异烟肼浓度低于阈值和体重<55 kg都是结核病治疗结果不良的危险因素。只有 4.4% 的参与者治疗失败。结论 尽管抗结核药物浓度低并不会导致治疗失败的患者比例较高，但低浓度利福平和异烟肼与培养物转化延迟之间的关联可能对结核病传播产生影响。 临床试验注册：NCT01782950。