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. Findings 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). Interpretation 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.

中文翻译：

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通过计算机辅助胸部 X 光检查和尿液 LAM 对入院的成人 HIV 患者增强结核病诊断（CASTLE 研究）：一项整群随机试验


背景 入院的艾滋病毒感染者（PHIV）死亡率很高，其中结核病（TB）是主要死因。系统地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结果。方法 我们对马拉维 Zomba 中心医院收治的成人 PHIV 患者进行了一项整群随机试验。入院日被随机分配为：使用尿液阿拉伯脂甘露聚糖 (LAM) 抗原测试（SILVAMP-LAM，Fujifilm，日本和Determine-LAM，Alere/Abbot，美国）增强结核病诊断，计算机辅助诊断数字化胸部 X 光检查 (dCXR) -CAD，CAD4TBv6，代尔夫特，荷兰），加上常规护理（“增强结核病诊断”）；或仅进行常规护理（“常规护理”）。主要结局是入院期间开始结核病治疗。次要结局是 56 天死亡率、24 小时内诊断出结核病以及出院时通过一份入院痰样本培养确定的未确诊结核病。调查结果 2020 年 9 月 2 日至 2022 年 2 月 15 日期间，我们招募了 419 名员工。四人在招募后被排除，在修改后的意向治疗分析中，在 207 个随机分配的入院日期间招募了 415 名成年人。入院时，90.8% (377/415) 正在接受抗逆转录病毒治疗 (ART)，CD4 细胞计数中位数 (IQR) 为 240 个细胞/mm3。在增强诊断组中，CAD4TBv6 评分中位数为 60（IQR：51-71），4.4% (9/207) 的患者 SILVAMP-LAM 呈阳性，14.4% (29/201) 的尿液 Define-LAM 呈阳性，其中三个样本呈阳性通过两次尿液测试。强化结核病诊断组中有 46/208 (22%) 的患者开始了结核病治疗，而常规护理组中有 24/207 (12%) 的患者开始了结核病治疗（风险比 [RR] 1.92，95% CI 1.20-3.08）。 56 天时死亡率没有差异（强化结核病诊断：54/208，26%；常规护理：52/207，25%；风险比 1.05，95% CI 0.72-1。53）； 24 小时内开始结核病治疗（强化结核病诊断：8/207，3.9%；常规护理：5/208，2.4%；RR 1.61，95% CI 0.53–4.71）；或出院时未确诊的微生物学确诊结核病（强化结核病诊断，0/207 (0.0%)，常规护理组 2/208 (1.0%) (p = 0.50)。解读尿液 SILVAMP-LAM/Determine-LAM 加 dCXR-CAD与常规护理相比，诊断发现更多住院的 PHIV 患者出现结核病治疗，这主要是由于更多地使用了 Define-LAM，而不是 SILVAMP-LAM 或 dCXR-CAD。进一步调查显示，成人艾滋病毒感染者的住院死亡率仍然很高，令人无法接受。