Effect of Antiretroviral Therapy on Treatment Outcomes in a Prospective Study of Extensively Drug-Resistant Tuberculosis (XDR-TB) HIV Coinfection Treatment in KwaZulu-Natal, South Africa.
Effect of Antiretroviral Therapy on Treatment Outcomes in a Prospective Study of Extensively Drug-Resistant Tuberculosis (XDR-TB) HIV Coinfection Treatment in KwaZulu-Natal, South Africa.
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DOI：
10.1097/qai.0000000000001833
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发表时间：
2018-12-01
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影响因子：
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通讯作者：
OʼDonnell MR
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作者：
Yuengling KA;Padayatchi N;Wolf A;Mathema B;Brown T;Horsburgh CR;OʼDonnell MR
广泛耐药结核病 (XDR-TB)/HIV 双重感染与高死亡率和不良结核病结局相关。我们进行了一项前瞻性研究，以全面描述一组广泛耐药结核病患者的特征。成年广泛耐药结核病患者在南非夸祖鲁-纳塔尔省的一家结核病转诊医院开始接受治疗，并进行随访直至治疗结束。每月收集临床数据、问卷、依从性数据和痰液。对基线结核分枝杆菌 (MTB) 分离株进行全基因组测序 (WGS)。使用标准定义来定义治疗结果。 2009 年 8 月至 2011 年 7 月期间，纳入了 105 名广泛耐药结核病患者（76.1%感染了 HIV）。在 HIV 合并感染患者中，82.5% 的患者最初接受了 ART，在研究期间累计接受了 ART 治疗的患者为 93.8%。 24 个月时，31.4% 的患者获得成功，68.6% 的患者获得不成功，死亡率为 41%。 ART 与 HIV 合并感染患者的死亡率改善相关 (p = 0.05)，结核培养转化率也与此相关 (p <0.0001)。在全基因组测序中，大多数菌株属于 LAM4/KZN 谱系 (68%)，几乎没有 SNP 差异。尽管艾滋病毒护理有所改善，但与之前的南非广泛耐药结核病/艾滋病毒治疗队列相比，治疗结果和死亡率仅略有改善。值得注意的是，这项研究是在引入新的抗分枝杆菌药物（例如贝达喹啉、德拉米尼）之前完成的。随着新的结核病药物和治疗方案的出现，监测治疗以确保在高负担、低资源环境中重现临床试验中看到的益处非常重要。
Extensively drug-resistant tuberculosis (XDR-TB)/HIV co-infection has been associated with high mortality and poor TB outcomes. We performed a prospective study to comprehensively characterize a cohort of XDR-TB patients. Adult XDR-TB patients were enrolled at treatment initiation at a TB referral hospital in KwaZulu-Natal Province, South Africa and followed through the end of treatment. Clinical data, questionnaires, adherence data, and sputum were collected monthly. Whole genome sequencing (WGS) was performed on baseline M. tuberculosis (MTB) isolates. Treatment outcomes were defined using standard definitions. 105 XDR-TB patients (76.1%HIV infected) were enrolled from August 2009 through July 2011. Among HIV co-infected patients, 82.5% were on ART initially and 93.8% cumulatively over the study period. At 24 months 31.4% had a successful outcome and 68.6% had an unsuccessful outcome with 41% mortality. ART was associated with improved mortality in HIV co-infected patients (p= 0.05), as was TB culture conversion (p <0.0001). On WGS the majority of strains were LAM4/KZN lineage (68%), with few SNP differences. Despite improved HIV care, treatment outcomes and mortality were only modestly improved compared to previous South African XDR-TB/HIV treatment cohorts. Of note this study was completed prior to introduction of new antimycobacterial agents (e.g. bedaquiline, delaminid). As new TB drugs and regimens become available it is important to monitor treatment to ensure benefits seen in clinical trials are reproduced in high-burden, low-resource settings.