耐多药结核病和 HIV 成人的死亡率与抗逆转录病毒治疗和抗结核药物使用情况：一项个体患者数据荟萃分析。
Mortality in adults with multidrug-resistant tuberculosis and HIV by antiretroviral therapy and tuberculosis drug use: an individual patient data meta-analysis.
机构信息
Department of Medicine and Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Social Medicine Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil; Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada.
出版信息
Lancet. 2020 Aug 8;396(10248):402-411. doi: 10.1016/S0140-6736(20)31316-7.
BACKGROUND
HIV-infection is associated with increased mortality during multidrug-resistant tuberculosis treatment, but the extent to which the use of antiretroviral therapy (ART) and anti-tuberculosis medications modify this risk are unclear. Our objective was to evaluate how use of these treatments altered mortality risk in HIV-positive adults with multidrug-resistant tuberculosis.
METHODS
We did an individual patient data meta-analysis of adults 18 years or older with confirmed or presumed multidrug-resistant tuberculosis initiating tuberculosis treatment between 1993 and 2016. Data included ART use and anti-tuberculosis medications grouped according to WHO effectiveness categories. The primary analysis compared HIV-positive with HIV-negative patients in terms of death during multidrug-resistant tuberculosis treatment, excluding those lost to follow up, and was stratified by ART use. Analyses used logistic regression after exact matching on country World Bank income classification and drug resistance and propensity-score matching on age, sex, geographic site, year of multidrug-resistant tuberculosis treatment initiation, previous tuberculosis treatment, directly observed therapy, and acid-fast-bacilli smear-positivity to obtain adjusted odds ratios (aORs) and 95% CIs. Secondary analyses were conducted among those with HIV-infection.
FINDINGS
We included 11 920 multidrug-resistant tuberculosis patients. 2997 (25%) were HIV-positive and on ART, 886 (7%) were HIV-positive and not on ART, and 1749 (15%) had extensively drug-resistant tuberculosis. By use of HIV-negative patients as reference, the aOR of death was 2·4 (95% CI 2·0-2·9) for all patients with HIV-infection, 1·8 (1·5-2·2) for HIV-positive patients on ART, and 4·2 (3·0-5·9) for HIV-positive patients with no or unknown ART. Among patients with HIV, use of at least one WHO Group A drug and specific use of moxifloxacin, levofloxacin, bedaquiline, or linezolid were associated with significantly decreased odds of death.
INTERPRETATION
Use of ART and more effective anti-tuberculosis drugs is associated with lower odds of death among HIV-positive patients with multidrug-resistant tuberculosis. Access to these therapies should be urgently pursued.
FUNDING
American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America.
背景
HIV 感染与耐多药结核病治疗期间的死亡率增加有关，但抗逆转录病毒疗法（ART）和抗结核药物的使用在多大程度上改变了这种风险尚不清楚。我们的目的是评估这些治疗方法如何改变 HIV 阳性耐多药结核病成人的死亡风险。
方法
我们对 1993 年至 2016 年间确诊或疑似耐多药结核病的 18 岁及以上成年人进行了一项个体患者数据荟萃分析。数据包括根据世界卫生组织（WHO）疗效类别分组的 ART 使用和抗结核药物。主要分析比较了 HIV 阳性和 HIV 阴性患者在耐多药结核病治疗期间的死亡情况，排除了失访患者，并根据 ART 使用情况进行了分层。分析使用逻辑回归在国家世界银行收入分类和耐药性上进行精确匹配，在年龄、性别、地理地点、耐多药结核病治疗开始年份、既往结核病治疗、直接观察治疗和抗酸杆菌涂片阳性上进行倾向评分匹配，以获得调整后的优势比（aOR）和 95%CI。在 HIV 感染患者中进行了二次分析。
结果
我们纳入了 11920 例耐多药结核病患者。2997 例（25%）为 HIV 阳性且正在接受 ART 治疗，886 例（7%）为 HIV 阳性但未接受 ART 治疗，1749 例（15%）为广泛耐药结核病。以 HIV 阴性患者为参照，所有 HIV 感染患者的死亡比值比（aOR）为 2.4（95%CI 2.0-2.9），HIV 阳性接受 ART 治疗患者的 aOR 为 1.8（1.5-2.2），而 HIV 阳性且未接受或未知 ART 治疗患者的 aOR 为 4.2（3.0-5.9）。在 HIV 阳性患者中，使用至少一种 WHO 分组 A 药物以及莫西沙星、左氧氟沙星、贝达喹啉或利奈唑胺的特定使用与死亡几率显著降低相关。
结论
ART 和更有效的抗结核药物的使用与 HIV 阳性耐多药结核病患者的死亡几率降低有关。迫切需要获得这些治疗方法。
资助
美国胸科学会、加拿大卫生研究院、美国疾病控制与预防中心、欧洲呼吸学会、传染病学会。
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