Clofazimine in the treatment of extensively drug-resistant tuberculosis with HIV coinfection in South Africa: a retrospective cohort study.
Clofazimine in the treatment of extensively drug-resistant tuberculosis with HIV coinfection in South Africa: a retrospective cohort study.
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DOI：
10.1093/jac/dku235
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发表时间：
2014-11
期刊：
影响因子：
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通讯作者：
N. Padayatchi;M. Gopal;R. Naidoo;L. Werner;K. Naidoo;I. Master;M. O’Donnell
中科院分区：
文献类型：
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作者：
N. Padayatchi;M. Gopal;R. Naidoo;L. Werner;K. Naidoo;I. Master;M. O’Donnell
广泛耐药（XDR）结核病（TB）和HIV合并感染与低治愈率和高死亡率相关。氯法齐明在体外已显示出抗结核分枝杆菌的活性，但氯法齐明在广泛耐药结核病和艾滋病毒合并感染中的临床经验有限。方法：这是一项对南非夸祖鲁-纳塔尔省成年广泛耐药结核病患者的回顾性队列研究，这些患者接受氯法齐明或不含氯法齐明的广泛耐药结核病治疗方案。主要结局指标为6个月时结核培养转化。生存分析和多变量逻辑回归比较了不同层次的时间与事件，并确定了结核培养转化的危险因素。结果2009年8月至2011年7月，85例符合条件的广泛耐药结核患者开始接受广泛耐药结核治疗。大多数患者（86%）感染艾滋病毒并接受抗逆转录病毒治疗（90%）。接受含氯法齐明方案的患者（n = 50）的培养转化率（40%）高于接受不含氯法齐明方案的患者（n = 35）（28.6%）。多因素分析显示，接受氯法齐明治疗组6个月时结核培养转化率增加2倍（危险率比2.54,95% CI 0.99-6.52, P = 0.05）。氯法齐明引起的不良反应很轻微，很少危及生命。结论氯法齐明在治疗广泛耐药结核/艾滋病毒中与提高培养转化有关。不良反应轻微且不危及生命。基于这些初步数据，氯法齐明在广泛耐药结核/艾滋病毒治疗中的进一步研究是有必要的。鉴于目前广泛耐药结核病治疗中培养物转化率较低，我们建议将氯法齐明纳入广泛耐药结核病治疗方案。
BACKGROUND Extensively drug-resistant (XDR) tuberculosis (TB) and HIV coinfection is associated with low cure rates and high mortality. Clofazimine has shown activity in vitro against Mycobacterium tuberculosis, but clinical experience with clofazimine in XDR-TB and HIV coinfection is limited. METHODS This was a retrospective cohort study of adult XDR-TB patients in KwaZulu-Natal, South Africa, treated with either a clofazimine- or non-clofazimine-containing XDR-TB treatment regimen. The primary outcome measure was TB culture conversion at 6 months. Survival analysis and multivariate logistic regression compared time to event in different strata and identified risk factors for TB culture conversion. RESULTS Between August 2009 and July 2011, eligible XDR-TB patients (n = 85) were initiated on treatment for XDR-TB. Most patients (86%) were HIV-infected and receiving antiretroviral therapy (90%). Patients receiving a clofazimine-containing regimen (n = 50) had a higher percentage of culture conversion (40%) compared with patients (n = 35) receiving a non-clofazimine regimen (28.6%). On multivariate analysis, there was a 2-fold increase in TB culture conversion at 6 months (hazard rate ratio 2.54, 95% CI 0.99-6.52, P = 0.05) in the group receiving a clofazimine-containing regimen. Adverse effects due to clofazimine were minor and rarely life-threatening. CONCLUSIONS Clofazimine was associated with improved culture conversion in the treatment of XDR-TB/HIV. Adverse effects were minor and non-life-threatening. Based on these preliminary data, further study of clofazimine in XDR-TB/HIV treatment is warranted. Given the present low rates of culture conversion in XDR-TB treatment, we recommend empirical inclusion of clofazimine in treatment regimens for XDR-TB.