BACKGROUND Diagnostic delays for tuberculosis are common, with high resultant mortality. Urine-Xpert Ultra (Cepheid) could improve time to diagnosis of tuberculosis disease and rifampicin resistance. We previously reported on lot-to-lot variation of the Fujifilm SILVAMP TB LAM. In this prespecified secondary analysis of the same cohort, we aimed to determine the diagnostic yield and accuracy of Urine-Xpert Ultra for tuberculosis in people with HIV, compared with an extended microbiological reference standard (eMRS) and composite reference standard (CRS) and also compared with Determine TB LAM Ag (AlereLAM, Abbott). METHODS In this prospective, multicentre, diagnostic accuracy study, we recruited consecutive inpatients and outpatients (aged ≥18 years) with HIV from 13 hospitals and clinics in seven countries (Malawi, South Africa, Tanzania, Thailand, Uganda, Viet Nam, and Zambia). Patients with no isoniazid preventive therapy in the past 6 months and fewer than three doses of tuberculosis treatment in the past 60 days were included. Reference and index testing was performed in real time. The primary outcome of this secondary analysis was the diagnostic yield and accuracy of Urine-Xpert Ultra compared with the eMRS and CRS. Diagnostic accuracy was compared with AlereLAM and diagnostic yield was compared with both AlereLAM and Sputum-Xpert Ultra. This study was registered with ClinicalTrials.gov, NCT04089423, and is complete. FINDINGS Between Dec 13, 2019, and Aug 5, 2021, 3528 potentially eligible individuals were screened and 1731 were enrolled, of whom 1602 (92·5%) were classifiable by the eMRS (median age 40 years [IQR 33-48], 838 [52·3%] of 1602 were female, 764 [47·7%] were male, 937 [58·5%] were outpatients, 665 [41·5%] were inpatients, median CD4 count was 374 cells per μL [IQR 138-630], and 254 [15·9%] had microbiologically confirmed tuberculosis). Against eMRS as reference, sensitivities of Urine-Xpert Ultra and AlereLAM were 32·7% (95% CI 27·2-38·7) and 30·7% (25·4-36·6) and specificities were 98·0% (97·1-98·6) and 90·4% (88·7-91·8), respectively. Against CRS as reference, sensitivities of Urine-Xpert Ultra and AlereLAM were 21·1% (95% CI 17·6-25·1), and 30·5% (26·4-34·9), and specificities were 99·1% (98·3-99·6) and 95·1% (93·5-96·3), respectively. The combination of Sputum-Xpert Ultra with AlereLAM or Urine-Xpert Ultra diagnosed 202 (77·1%) and 204 (77·9%) of 262 eMRS-positive participants, respectively, in incompletely overlapping groups; combining all three tests diagnosed 214 (81·7%) of 262 eMRS-positive participants INTERPRETATION: Urine-Xpert Ultra could offer promising clinical utility in addition to AlereLAM and Sputum-Xpert Ultra. In inpatient settings where both AlereLAM and Urine-Xpert Ultra are possible, both should be offered to support rapid diagnosis and treatment. FUNDING Global Health Innovative Technology Fund, KfW Development Bank, Commonwealth of Australia represented by the Department of Foreign Affairs and Trade, and the Netherlands Enterprise Agency.

中文翻译：

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Urine-Xpert Ultra 用于诊断 HIV 感染者结核病：一项前瞻性、多中心、诊断准确性研究。


背景 结核病的诊断延误很常见，死亡率很高。Urine-Xpert Ultra （Cepheid） 可以缩短结核病和利福平耐药的诊断时间。我们之前报道过 Fujifilm SILVAMP TB LAM 的批次间差异。在对同一队列进行的这项预先指定的二次分析中，我们旨在确定 Urine-Xpert Ultra 对 HIV 感染者结核病的诊断率和准确性，与扩展微生物学参考标准 （eMRS） 和复合参考标准 （CRS） 进行比较，并与确定结核病 LAM Ag （AlereLAM， Abbott） 进行比较。方法 在这项前瞻性、多中心、诊断准确性研究中，我们从 7 个国家 （马拉维、南非、坦桑尼亚、泰国、乌干达、越南 和赞比亚） 的 13 家医院和诊所招募了连续的 HIV 住院和门诊患者 （≥18 岁）。纳入过去 6 个月内未接受异烟肼预防治疗且过去 60 天内接受结核病治疗少于 3 剂的患者。实时进行参考和指数测试。这项二次分析的主要结局是 Urine-Xpert Ultra 与 eMRS 和 CRS 相比的诊断率和准确性。将诊断准确性与 AlereLAM 进行比较，并将诊断率与 AlereLAM 和 Sputum-Xpert Ultra 进行比较。这项研究已在 ClinicalTrials.gov， NCT04089423 注册，现已完成。 结果在 2019 年 12 月 13 日至 2021 年 8 月 5 日期间，筛选了 3528 名可能符合条件的个体，并纳入了 1731 名受试者，其中 1602 名 （92·5%） 可按 eMRS 分类（中位年龄 40 岁 [IQR 33-48]，1602 名患者中有 838 名 [52·3%] 为女性，764 名 [47·7%] 为男性，937 名 [58·5%] 为门诊患者，665 名 [41·5%] 为住院患者， 中位 CD4 计数为 374 个细胞/μL [IQR 138-630]，254 [15·9%] 经微生物学证实为结核病）。以 eMRS 为参考，Urine-Xpert Ultra 和 AlereLAM 的敏感性为 32·7% （95% CI 27·2-38·7） 和 30·7% （25·4-36·6），特异性分别为 98·0% （97·1-98·6） 和 90·4% （88·7-91·8）。以 CRS 为参考，Urine-Xpert Ultra 和 AlereLAM 的敏感性为 21·1% （95% CI 17·6-25·1） 和 30·5% （26·4-34·9），特异性分别为 99·1% （98·3-99·6） 和 95·1% （93·5-96·3）。Sputum-Xpert Ultra 与 AlereLAM 或 Urine-Xpert Ultra 的组合在不完全重叠的组中分别诊断了 262 名 eMRS 阳性参与者中的 202 名 （77·1%） 和 204 名 （77·9%）;结合所有三项测试诊断出 214 名 eMRS 阳性参与者中的 81 名 （7·262） 解释：除了 AlereLAM 和 Sputum-Xpert Ultra 之外，Urine-Xpert Ultra 还可以提供有前途的临床实用性。在同时使用 AlereLAM 和 Urine-Xpert Ultra 的住院环境中，应同时提供这两种药物以支持快速诊断和治疗。资助全球健康创新技术基金、德国复兴信贷银行、澳大利亚外交贸易部代表的澳大利亚联邦以及荷兰企业局。