Determine TB-LAM point-of-care tuberculosis assay predicts poor outcomes in outpatients during their first year of antiretroviral therapy in South Africa

Abstract

Background: Determine TB-LAM is the first point-of-care test (POC) for HIV-associated tuberculosis (TB) and rapidly identifies TB in those at high-risk for short-term mortality. While the relationship between urine-LAM and mortality has been previously described, the outcomes of those undergoing urine-LAM testing have largely been assessed during short follow-up periods within diagnostic accuracy studies. We therefore sought to assess the relationship between baseline urine-LAM results and subsequent hospitalization and mortality under real-world conditions among outpatients in the first year of ART. Methods: Consecutive, HIV-positive adults with a CD4 count < 100 cells/uL presenting for ART initiation were enrolled. TB diagnoses and outcomes (hospitalization, loss-to-follow and mortality) were recorded during the first year following enrolment. Baseline urine samples were retrospectively tested using the urine-LAM POC assay. Kaplan Meier survival curves were used to assess the cumulative probability of hospitalization or mortality in the first year of follow-up, according to urine-LAM status. Cox regression analyses were performed to determine independent predictors of hospitalization and mortality at three months and one year of follow-up.

Performance of Tuberculosis Molecular Bacterial Load Assay Compared to Alere TB-LAM in Urine of Pulmonary Tuberculosis Patients with HIV Co-Infections

“…Moreover, the extent of infections or kidney impairments that would allow the excretion of M. tb cells in urine is not yet known, and this may differ from one patient to another and with individual patients’ immune systems. Low CD4 cell counts below 200 cells/uL have been associated with LAM positivity [ 22 , 23 , 24 ]. However, it is of note that only 37.5% of patients with positive LAM results had CD4 cell counts <200 cells/µL.…”

Addressing TB-related mortality in adults living with HIV: a review of the challenges and potential solutions

“… 89 A Cochrane review analyzing two RCTs in inpatient settings and one RCT in outpatient settings, all in sub-Saharan Africa, reported that the use of LAM as part of a TB diagnostic strategy likely reduces mortality at 8 weeks and probably results in a slight increase in TB treatment initiation in PLHIV in inpatient settings, and that the use of LAM as part of a TB diagnostic strategy may reduce mortality at 6 months and may result in a large increase in TB treatment initiation in PLHIV in outpatient settings. 90 LAM is hypothesized to indirectly lead to increased mortality risk in people with HIV/TB co-infection, as increased LAM levels were found to contribute to the survival of M. tuberculosis in macrophages, 91 and PLHIV with a positive LAM result account for a disproportionate proportion of those who die, 92 which may reflect the association between detection of LAM and a lower CD4 count. 90 A cost-effectiveness analysis demonstrated that urine-based TB screening using LAM in hospitalized patients with HIV could increase life expectancy and be cost-effective in resource-limited settings.…”