Expanding Xpert MTB/RIF Ultra and lateral flow urine lipoarabinomannan testing for diagnosis of tuberculosis among adults living with HIV admitted to hospitals in Tanzania and Mozambique (EXULTANT): a randomised controlled trial.

BACKGROUND: Tuberculosis is the main cause of death among hospitalised people living with HIV. Non-sputum-based diagnostics could improve patient outcomes. The EXULTANT trial aims to evaluate an expanded tuberculosis screening strategy among people with HIV in two African countries with a high tuberculosis and HIV burden.

METHODS: This pragmatic, individually randomised controlled superiority trial was conducted across 11 hospitals in Tanzania and Mozambique. We consecutively enrolled adults living with HIV (aged ≥18 years) without an existing tuberculosis diagnosis or recent tuberculosis treatment, within 24 h of admission. The intervention group underwent Xpert MTB/RIF Ultra (Xpert Ultra) testing from sputum, stool, and urine, plus lateral flow urine lipoarabinomannan (LF-LAM) testing (Determine TB LAM Ag assay), irrespective of symptoms. The control group followed standard-of-care, symptom-based, WHO-recommended sputum Xpert Ultra and LF-LAM testing. The primary endpoint was the proportion of participants with microbiologically confirmed tuberculosis starting treatment within 72 h. Secondary endpoints included 8-week all-cause mortality and time to tuberculosis diagnosis. The trial is registered at ClinicalTrials.gov (NCT04568967) and is completed.

FINDINGS: From Sept 25, 2022, to March 15, 2024, we screened 1534 participants, and randomly assigned 1172 (76·6%) to either the intervention group (n=582) or the control group (n=590). At admission, 715 participants (61·0%) were female, 845 (75·4%) were on antiretroviral therapy (ART), and median CD4 count was 232 cells per μL (IQR 87-490). In the control group, 505 (85·6%) had tuberculosis-compatible symptoms and were eligible for sputum Xpert Ultra testing (306 of them [60·6%] provided a sample) and 538 (91·2%) met WHO criteria for LF-LAM testing. In the intention-to-treat analysis, 93 (16·0%) of 582 participants in the intervention group and 90 (15·3%) of 590 in the control group had microbiologically confirmed tuberculosis and started treatment within 72 h (difference 0·7%, 95% CI -3·4 to 4·8, p=0·73). 8-week all-cause mortality was 25·8% (150 of 582) in the intervention group and 28·8% (170 of 590) in the control group (hazard ratio 0·86, 95% CI 0·69 to 1·07, p=0·18). Median time to tuberculosis treatment initiation was 0·98 days (IQR 0·83-1·92) and 0·92 days (0·79-1·86) in the intervention and control groups, respectively (hazard ratio 1·05, 95% CI 0·82 to 1·33, p=0·72).

INTERPRETATION: An expanded screening strategy among people living with HIV admitted to hospital did not increase the proportion of individuals with microbiologically confirmed tuberculosis starting treatment or reduce 8-week mortality.

FUNDING: EDCTP2 programme, supported by the EU.