Diagnosing tuberculosis in hospitalized HIV-infected individuals who cannot produce sputum: is urine lipoarabinomannan testing the answer?

Abstract

BackgroundUp to one third of HIV-infected individuals with suspected TB are sputum-scarce. The Alere Determine™ TB LAM Ag lateral flow strip test can be used to diagnose TB in HIV-infected patients with advanced immunosuppression. However, how urine LAM testing should be incorporated into testing algorithms and in the context of specific patient sub-groups remains unclear.MethodsThis study represents a post hoc sub-group analysis of data from a randomized multi-center parent study. The study population consisted of hospitalized HIV-infected patients with suspected TB who were unable to produce sputum and who underwent urine LAM testing. The diagnostic utility of urine LAM for TB in this group was compared to the performance of urine LAM in patients who did produce a sputum sample in the parent study.ResultsThere were a total of 187 and 2341 patients in the sputum-scarce and sputum-producing cohorts, respectively. 80 of the sputum-scarce patients underwent testing with urine LAM. In comparison to those who did produce sputum, sputum-scarce patients had a younger age, a lower Karnofsky performance score, and a lower weight and BMI at admission. A greater proportion of sputum-scarce patients were urine LAM positive, compared to those who were able to produce sputum (31% vs. 21%, p = 0.04). A higher proportion of sputum-scarce patients died within 8 weeks of admission (32% vs. 24%, p = 0.013). We inferred that 19% of HIV-infected sputum-scarce patients suspected of TB were diagnosed with tuberculosis by urine LAM testing, with an estimated positive predictive value of 63% (95% CI 43–82%).ConclusionsUrine LAM testing can effectively identify tuberculosis in HIV-infected patients who are at a higher risk of mortality yet are unable to generate a sputum sample for diagnostic testing. Our findings support the use of urine LAM testing in sputum-scarce hospitalized HIV-infected patients, and its incorporation into diagnostic algorithms for this patient population.

An Optimal Diagnostic Strategy for Tuberculosis in Hospitalized HIV-Infected Patients Using GeneXpert MTB/RIF and Alere Determine TB LAM Ag

“…As such, the consequences of initiating treatment unnecessarily must also be considered when a testing strategy is chosen, especially when there is an increased risk of adverse drug reactions, such as those associated with second-line TB treatment. Furthermore, in patients who are unable to expectorate sputum, LAM testing is the obvious first choice, and our findings in this subgroup (patients with scarce sputum) have been reported separately (25).…”

“…We confined our analysis to patients who could expectorate sputum, yet LAM may be most beneficial in those whose sputum is scarce or who have EPTB. However, the main aim of our study was to inform diagnostic algorithms in settings where other rapid sputum-based diagnostics, such as Xpert, were available, and the findings in patients with scarce sputum were published elsewhere (25). Furthermore, this was a post hoc analysis, utilizing a limited subset of the patients recruited into the parent study, which may limit generalizability of the findings.…”

Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in people living with HIV

“…When restricting analysis to studies that included participants unable to produce a sputum sample, the estimates of sensitivity increased. Sputum‐scarce patients may be the potential target population to benefit the most from urine‐based testing as they cannot have other sputum‐based diagnostic testing and are likely to have a high yield of urine lipoarabinomannan (LAM) test positivity (Sabur 2017). However, only a few studies included participants who could not provide sputum samples for diagnostic testing.…”

Point-of-Care HIV Viral Load Testing: an Essential Tool for a Sustainable Global HIV/AIDS Response

“…Offering a package of services to identify patients with advanced HIV disease (defined as CD4 count less than 200 cells/ml) and test for common opportunistic infections is critical (158). Fortunately, POC CD4 count, POC testing for TB using GeneXpert or the lipoarabinomannan (LAM) assay, and screening for cryptococcal meningitis using a cryptococcal antigen RDT are available (184,227,228).…”