Systematic or Test-Guided Treatment for Tuberculosis in HIV-Infected Adults
Systematic or Test-Guided Treatment for Tuberculosis in HIV-Infected Adults
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DOI：
10.1056/nejmoa1910708
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发表时间：
2020-06-18
影响因子：
158.5
通讯作者：
Laureillard, Didier
中科院分区：
文献类型：
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作者：
Blanc, Francois-Xavier;Badje, Anani D.;Laureillard, Didier
一项涉及CD 4 + T细胞计数低于每立方毫米100个细胞的HIV感染患者的试验比较了结核病的系统治疗策略和仅在检测显示感染时进行治疗的策略。系统的治疗并不比治疗指导的测试方面的死亡率或细菌infection.Background在结核病和人类免疫缺陷病毒（HIV）的高负担的地区，许多HIV感染的成年人开始抗逆转录病毒治疗（ART）时，他们已经严重免疫功能低下。在这些患者中，ART开始后的死亡率很高，结核病和侵入性细菌疾病是常见的死亡原因。方法我们进行了一项为期48周的结核病经验性治疗试验，并与在以前未接受过抗逆转录病毒治疗且CD 4 + T细胞计数低于100个细胞/立方毫米的HIV感染成人中通过检测指导的治疗进行了比较。1例接受筛查（Xpert MTB/RIF检测，尿脂阿拉伯甘露聚糖检测，和胸部X线摄影）以确定是否应该开始结核病治疗或接受利福平、异烟肼、乙胺丁醇和吡嗪酰胺每日给药2个月，随后利福平和异烟肼每日给药4个月。主要终点是随机分组后24周内（主要分析）或48周内任何原因或侵袭性细菌性疾病导致的死亡。结果系统治疗组522例，指导治疗组525例，治疗24周时，（计算为每100患者年的首次事件数），系统治疗组为19.4，指导治疗组为20.3（调整后的风险比，0.95; 95%置信区间[CI]，0.63至1.44）。第48周时，相应的发生率为12.8和13.3（校正后的风险比，0.97 [95% CI，0.67 - 1.40]）。在第24周，系统治疗组的结核病发生概率低于指导治疗组（3.0% vs. 17.9%;校正风险比，0.15; 95% CI，0.09 - 0.26），但系统治疗组发生3级或4级药物相关不良事件的概率更高（17.4% vs. 7.2%;校正风险比2.57; 95%CI，1.75 - 3.78）。严重不良事件在系统治疗中更常见。结论在既往未接受ART治疗的严重免疫抑制的HIV感染成人中，结核病系统治疗在降低24或48周死亡率或侵袭性细菌性疾病发生率方面并不上级检测指导治疗，并且与更多的3级或4级不良事件相关。（由Agence Nationale de Recherches sur le Sida et les Hepatites Virales资助; STATIS ANRS 12290 ClinicalTrials.gov编号，。
A trial involving HIV-infected patients with CD4+ T-cell counts below 100 cells per cubic millimeter compared strategies of systematic treatment for TB and treatment only if testing revealed infection. Systematic treatment was not better than treatment guided by testing with respect to the rate of death or bacterial infection.Background In regions with high burdens of tuberculosis and human immunodeficiency virus (HIV), many HIV-infected adults begin antiretroviral therapy (ART) when they are already severely immunocompromised. Mortality after ART initiation is high in these patients, and tuberculosis and invasive bacterial diseases are common causes of death. Methods We conducted a 48-week trial of empirical treatment for tuberculosis as compared with treatment guided by testing in HIV-infected adults who had not previously received ART and had CD4+ T-cell counts below 100 cells per cubic millimeter.Patients recruited in Ivory Coast, Uganda, Cambodia, and Vietnam were randomly assigned in a 1:1 ratio to undergo screening (Xpert MTB/RIF test, urinary lipoarabinomannan test, and chest radiography) to determine whether treatment for tuberculosis should be started or to receive systematic empirical treatment with rifampin, isoniazid, ethambutol, and pyrazinamide daily for 2 months, followed by rifampin and isoniazid daily for 4 months. The primary end point was a composite of death from any cause or invasive bacterial disease within 24 weeks (primary analysis) or within 48 weeks after randomization. Results A total of 522 patients in the systematic-treatment group and 525 in the guided-treatment group were included in the analyses.At week 24, the rate of death from any cause or invasive bacterial disease (calculated as the number of first events per 100 patient-years) was 19.4 with systematic treatment and 20.3 with guided treatment (adjusted hazard ratio, 0.95; 95% confidence interval [CI], 0.63 to 1.44). At week 48, the corresponding rates were 12.8 and 13.3 (adjusted hazard ratio, 0.97 [95% CI, 0.67 to 1.40]). At week 24, the probability of tuberculosis was lower with systematic treatment than with guided treatment (3.0% vs. 17.9%; adjusted hazard ratio, 0.15; 95% CI, 0.09 to 0.26), but the probability of grade 3 or 4 drug-related adverse events was higher with systematic treatment (17.4% vs. 7.2%; adjusted hazard ratio 2.57; 95% CI, 1.75 to 3.78).Serious adverse events were more common with systematic treatment. Conclusions Among severely immunosuppressed adults with HIV infection who had not previously received ART, systematic treatment for tuberculosis was not superior to test-guided treatment in reducing the rate of death or invasive bacterial disease over 24 or 48 weeks and was associated with more grade 3 or 4 adverse events.(Funded by the Agence Nationale de Recherches sur le Sida et les Hepatites Virales; STATIS ANRS 12290 ClinicalTrials.gov number,.)