Abstract：
BACKGROUND: People with HIV (PHIV) admitted to hospital have high mortality, with tuberculosis (TB) being the major cause of death. Systematic use of new TB diagnostics could improve TB diagnosis and might improve outcomes.
METHODS: We conducted a cluster randomised trial among adult PHIV admitted to Zomba Central Hospital, Malawi. Admission-days were randomly assigned to: enhanced TB diagnostics using urine lipoarabinomannan (LAM) antigen tests (SILVAMP-LAM, Fujifilm, Japan and Determine-LAM, Alere/Abbot, USA), digital chest X-ray with computer aided diagnosis (dCXR-CAD, CAD4TBv6, Delft, Netherlands), plus usual care (\"enhanced TB diagnostics\"); or usual care alone (\"usual care\"). The primary outcome was TB treatment initiation during admission. Secondary outcomes were 56-day mortality, TB diagnosis within 24-hours, and undiagnosed TB at discharge, ascertained by culture of one admission sputum sample.
RESULTS: Between 2 September 2020 and 15 February 2022, we recruited 419 people. Four people were excluded post-recruitment, leaving 415 adults recruited during 207 randomly assigned admission-days in modified intention-to-treat analysis. At admission, 90.8% (377/415) were taking antiretroviral therapy (ART) with median (IQR) CD4 cell count 240 cells/mm3. In the enhanced diagnostic arm, median CAD4TBv6 score was 60 (IQR: 51-71), 4.4% (9/207) had SILVAMP-LAM-positive and 14.4% (29/201) had Determine-LAM positive urine with three samples positive by both urine tests. TB treatment was initiated in 46/208 (22%) in enhanced TB diagnostics arm and 24/207 (12%) in usual care arm (risk ratio [RR] 1.92, 95% CI 1.20-3.08). There was no difference in mortality by 56 days (enhanced TB diagnosis: 54/208, 26%; usual care: 52/207, 25%; hazard ratio 1.05, 95% CI 0.72-1.53); TB treatment initiation within 24 hours (enhanced TB diagnosis: 8/207, 3.9%; usual care: 5/208, 2.4%; RR 1.61, 95% CI 0.53-4.71); or undiagnosed microbiological-confirmed TB at discharge (enhanced TB diagnosis, 0/207 (0.0%), usual care arm 2/208 (1.0%) (p = 0.50).
CONCLUSIONS: Urine SILVAMP-LAM/Determine-LAM plus dCXR-CAD diagnostics identified more hospitalised PHIV with TB than usual care. The increase in TB treatment appeared mainly due to greater use of Determine-LAM, rather than SILVAMP-LAM or dCXR-CAD. Poor concordance between Determine-LAM and SILVAMP-LAM urine tests requires further investigation. Inpatient mortality for adults with HIV remains unacceptability high.
METHODS: We conducted a cluster randomised trial among adult PHIV admitted to Zomba Central Hospital, Malawi. Admission-days were randomly assigned to: enhanced TB diagnostics using urine lipoarabinomannan (LAM) antigen tests (SILVAMP-LAM, Fujifilm, Japan and Determine-LAM, Alere/Abbot, USA), digital chest X-ray with computer aided diagnosis (dCXR-CAD, CAD4TBv6, Delft, Netherlands), plus usual care (\"enhanced TB diagnostics\"); or usual care alone (\"usual care\"). The primary outcome was TB treatment initiation during admission. Secondary outcomes were 56-day mortality, TB diagnosis within 24-hours, and undiagnosed TB at discharge, ascertained by culture of one admission sputum sample.
RESULTS: Between 2 September 2020 and 15 February 2022, we recruited 419 people. Four people were excluded post-recruitment, leaving 415 adults recruited during 207 randomly assigned admission-days in modified intention-to-treat analysis. At admission, 90.8% (377/415) were taking antiretroviral therapy (ART) with median (IQR) CD4 cell count 240 cells/mm3. In the enhanced diagnostic arm, median CAD4TBv6 score was 60 (IQR: 51-71), 4.4% (9/207) had SILVAMP-LAM-positive and 14.4% (29/201) had Determine-LAM positive urine with three samples positive by both urine tests. TB treatment was initiated in 46/208 (22%) in enhanced TB diagnostics arm and 24/207 (12%) in usual care arm (risk ratio [RR] 1.92, 95% CI 1.20-3.08). There was no difference in mortality by 56 days (enhanced TB diagnosis: 54/208, 26%; usual care: 52/207, 25%; hazard ratio 1.05, 95% CI 0.72-1.53); TB treatment initiation within 24 hours (enhanced TB diagnosis: 8/207, 3.9%; usual care: 5/208, 2.4%; RR 1.61, 95% CI 0.53-4.71); or undiagnosed microbiological-confirmed TB at discharge (enhanced TB diagnosis, 0/207 (0.0%), usual care arm 2/208 (1.0%) (p = 0.50).
CONCLUSIONS: Urine SILVAMP-LAM/Determine-LAM plus dCXR-CAD diagnostics identified more hospitalised PHIV with TB than usual care. The increase in TB treatment appeared mainly due to greater use of Determine-LAM, rather than SILVAMP-LAM or dCXR-CAD. Poor concordance between Determine-LAM and SILVAMP-LAM urine tests requires further investigation. Inpatient mortality for adults with HIV remains unacceptability high.
摘要：
背景：住院的HIV（PHHIV）患者死亡率高，结核病（TB）是死亡的主要原因。系统使用新的结核病诊断方法可以改善结核病诊断并可能改善预后。
方法：我们在Zomba中心医院收治的成人HIV中进行了一项整群随机试验，马拉维。入院天数被随机分配到：使用尿脂阿拉伯甘露聚糖（LAM）抗原测试（SILVAMP-LAM，富士胶片,日本和确定林，Alere/Abbot,美国),计算机辅助诊断的数字胸部X线(dCXR-CAD，CAD4TBv6代尔夫特,荷兰),加上常规护理（“增强结核病诊断”）；或仅常规护理（“常规护理”）。主要结果是入院期间开始TB治疗。次要结果是56天死亡率，结核病诊断在24小时内，出院时未确诊的结核病，通过一个入院痰样本的培养确定。
结果：在2020年9月2日至2022年2月15日之间，我们招募了419人。招募后有四人被排除在外，将在207个随机分配的入院日期间招募的415名成年人留在改良的意向治疗分析中.入院时,90.8%(377/415)患者接受抗逆转录病毒治疗(ART),CD4细胞计数中位数(IQR)为240细胞/mm3。在增强型诊断臂中，CAD4TBv6的中位数为60分（IQR：51-71），4.4％（9/207）的SILVAMP-LAM阳性，而14.4％（29/201）的Determination-LAM阳性尿液中的三个样本均为两次尿液测试均为阳性。在增强型TB诊断组46/208(22%)和常规治疗组24/207(12%)开始TB治疗(风险比[RR]1.92,95%CI1.20-3.08)。56天的死亡率没有差异（增强的结核病诊断：54/208，26％；常规护理：52/207，25％；风险比1.05，95％CI0.72-1.53）；结核病治疗在24小时内开始（增强的结核病诊断：8/207，3.9％；常规护理：5/208，2.4％；RR1.61，95％CI0.53-4.71）；或出院时未诊断的微生物确认结核病（增强0/207（0.0%），常规护理臂2/208（1.0%）（p=0.50）。
结论：尿液SILVAMP-LAM/Determine-LAM加dCXR-CAD诊断发现，与常规治疗相比，住院的PDHIV合并TB更多。结核病治疗的增加主要是由于Determining-LAM的更多使用，而不是SILVAMP-LAM或DCXR-CAD。Determine-LAM和SILVAMP-LAM尿液测试之间的不良一致性需要进一步调查。艾滋病毒成人的住院死亡率仍然很高。
方法：我们在Zomba中心医院收治的成人HIV中进行了一项整群随机试验，马拉维。入院天数被随机分配到：使用尿脂阿拉伯甘露聚糖（LAM）抗原测试（SILVAMP-LAM，富士胶片,日本和确定林，Alere/Abbot,美国),计算机辅助诊断的数字胸部X线(dCXR-CAD，CAD4TBv6代尔夫特,荷兰),加上常规护理（“增强结核病诊断”）；或仅常规护理（“常规护理”）。主要结果是入院期间开始TB治疗。次要结果是56天死亡率，结核病诊断在24小时内，出院时未确诊的结核病，通过一个入院痰样本的培养确定。
结果：在2020年9月2日至2022年2月15日之间，我们招募了419人。招募后有四人被排除在外，将在207个随机分配的入院日期间招募的415名成年人留在改良的意向治疗分析中.入院时,90.8%(377/415)患者接受抗逆转录病毒治疗(ART),CD4细胞计数中位数(IQR)为240细胞/mm3。在增强型诊断臂中，CAD4TBv6的中位数为60分（IQR：51-71），4.4％（9/207）的SILVAMP-LAM阳性，而14.4％（29/201）的Determination-LAM阳性尿液中的三个样本均为两次尿液测试均为阳性。在增强型TB诊断组46/208(22%)和常规治疗组24/207(12%)开始TB治疗(风险比[RR]1.92,95%CI1.20-3.08)。56天的死亡率没有差异（增强的结核病诊断：54/208，26％；常规护理：52/207，25％；风险比1.05，95％CI0.72-1.53）；结核病治疗在24小时内开始（增强的结核病诊断：8/207，3.9％；常规护理：5/208，2.4％；RR1.61，95％CI0.53-4.71）；或出院时未诊断的微生物确认结核病（增强0/207（0.0%），常规护理臂2/208（1.0%）（p=0.50）。
结论：尿液SILVAMP-LAM/Determine-LAM加dCXR-CAD诊断发现，与常规治疗相比，住院的PDHIV合并TB更多。结核病治疗的增加主要是由于Determining-LAM的更多使用，而不是SILVAMP-LAM或DCXR-CAD。Determine-LAM和SILVAMP-LAM尿液测试之间的不良一致性需要进一步调查。艾滋病毒成人的住院死亡率仍然很高。
