Acquired rifamycin resistance with twice-weekly treatment of HIV-related tuberculosis
Acquired rifamycin resistance with twice-weekly treatment of HIV-related tuberculosis
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DOI：
10.1164/rccm.200503-417oc
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发表时间：
2006-02-01
影响因子：
24.7
通讯作者：
El-Sadr, W
中科院分区：
文献类型：
--
作者：
Burman, W;Benator, D;El-Sadr, W
理由。在治疗HIV相关结核病（TB）期间，推荐使用利福布汀代替利福平，以促进伴随的强效抗逆转录病毒治疗，但这种方法尚未在前瞻性研究中进行评估。目的：评价以利福布汀为基础的间歇性治疗的活性。培养确诊的结核病患者在直接监督下接受2个月的利福平、异烟肼、吡嗪酰胺和乙胺丁醇治疗（根据当地结核病控制计划，每天、每周三次或每周两次给药），随后是4个月的每周两次的利福布雷定加异烟肼（isoniazid. Measures）：培养阳性治疗失败或复发。大多数人患有晚期艾滋病毒疾病;中位CD 4细胞计数和HIV-RNA水平分别为90个细胞/mm 3（四分位数范围，35-175）和5.3 log（10）拷贝/ml（四分位数范围，4.8-5.7）。9例（5.3%）患者出现培养阳性治疗失败（n = 3）或复发（n = 6）。这9例病例中有8例（89%）分离株具有获得性利福霉素耐药。治疗失败或复发与基线CD 4淋巴细胞计数相关，在CD 4 < 100 cells/mm 3的患者中为12.3%（9/73; 95%置信区间，6.5-22.0%），而在CD 4淋巴细胞计数较高的患者中为0%（0/65; 95%置信区间，0.0-4.5%）（p < 0.01）。137例（81%）患者在结核病治疗期间接受了抗逆转录病毒治疗。不良事件是常见的，但只有两名患者（1%）永久停止studydrug.Conclusions：间歇性利福布丁为基础的治疗艾滋病毒相关的结核病，耐受性良好，但有一个高风险的治疗失败或复发与获得性利福霉素耐药低CD 4淋巴细胞计数的患者。
Rationale. Rifabutin was recommended in place of rifampin during treatment of HIV-related tuberculosis (TB) to facilitate concomitant potent antiretroviral therapy, but this approach has not been evaluated in a prospective study.Objective: To evaluate the activity of intermittent rifabutin-based therapy.Methods: Patients with culture-confirmed TB were treated under direct supervision with 2 mo of rifabutin, isoniazid, pyrazinamide, and ethambutol (given daily, thrice-weekly, or twice-weekly per the local tuberculosis control program), followed by 4 mo of twice-weekly rifabutin plus isoniazid.Measurements: Culture-positive treatment failure or relapse.Main Results: A total of 169 eligible patients were enrolled. Most had advanced HIV disease; the median CD4 cell count and HIV-RNA level were 90 cells/mm(3) (interquartile range, 35-175) and 5.3 log(10) copies/ml (interquartile range, 4.8-5.7), respectively. Nine (5.3%) patients had culture-positive treatment failure (n = 3) or relapse (n = 6). Eight of these nine (89%) cases had isolates with acquired rifamycin resistance. Treatment failure or relapse was associated with baseline CD4 lymphocyte count, being 12.3% (9/73; 95% confidence interval, 6.5-22.0%) among patients with CD4 < 100 cells/mm(3) versus 0% (0/65; 95% confidence interval, 0.0-4.5%) among those with higher CD4 lymphocyte counts (p < 0.01). One hundred thirty-seven (81%) patients received antiretroviral therapy during TB treatment. Adverse events were common, but only two patients (1%) permanently discontinued study drugs.Conclusions: Intermittent rifabutin-based therapy for HIV-related TB; was well tolerated, but there was a high risk of treatment failure or relapse with acquired rifamycin resistance among patients with low CD4 lymphocyte counts.