Claudia Denkinger, MD, PhD, on LAM Testing for Diagnosing TB in Patients With HIV
Earlier diagnosis and treatment of tuberculosis (TB) in people with HIV would significantly reduce the mortality rate among this population. However, current point-of-care (POC) tests are suboptimal. A new study evaluated a new test’s diagnostic accuracy of TB in people with HIV.
Lead author, Claudia M. Denkinger, MD, PhD, answered our questions about this research. Dr Denkinger is currently head of the Division of Tropical Medicine at the University Hospital Heidelberg in Germany. At the time of the study, she was head of the TB department at the Foundation for Innovative New Diagnostics (FIND) in Geneva, Switzerland.
INFECTIOUS DISEASES CONSULTANT: TB is common among patients with HIV, and therefore, having a point-of-care test for TB would make for a quicker diagnosis. Your study explored the possibility of a novel point-of-care test for TB. Can you tell us more about the study and its findings?
Claudia Denkinger: TB is not only common among people living with HIV, it is also the most common cause of death in this population, accounting for around 1 in 3 AIDS-related deaths. A POC test will enable a quick diagnosis and is critically needed, as there is still no single rapid, accurate, and robust TB diagnostic test available where patients first access care.
FIND and our partners conducted this study using biobanked urine samples from 3 independent prospective cohort studies of hospitalized patients living with HIV at 2 South African district hospitals. Diagnostic accuracy of both Fujifilm SILVAMP TB LAM (FujiLAM) and the commercially available Alere Determine™ TB LAM (Alere LAM) was determined against microbiological and composite reference standards (including clinical diagnoses).
The study found that the FujiLAM test had around 30% higher sensitivity than the Alere LAM test across the main population and in several subanalyses (including in different CD4 strata).
ID CON: How might these findings impact clinical practice and the diagnosis of TB in patients with HIV?
CD: TB is primarily a pulmonary infection and diagnosis is usually made based on sputum analysis, often conducted using GeneXpert® (Cepheid) or sputum smear microscopy. Data show that 20% to 60% of HIV-positive patients presenting for TB diagnosis are unable to produce a sputum sample, as HIV makes it difficult to produce the sputum sample needed for traditional diagnostics, and because TB outside the lung is more common in people living with HIV—in particular, in people who are severely immunocompromised. This often prevents patients from being diagnosed in a timely manner or diagnosed at all.
LAM-based tests rely on urine samples and would overcome this issue. As proven in one of the 3 cohorts in the study, FujiLAM would have been able to provide a diagnosis of TB for 65% of patients—and in combination with Xpert MTB/Rif for 72% of patients—within 24 hours of hospital admission. Diagnosis using Xpert alone would have been only able to identify 26% of patients in this time period, primarily because of the inability to obtain a sputum sample.
Furthermore, AlereLAM has previously demonstrated survival benefit, and this study suggests that more sensitive urine-based LAM tests such as FujiLAM have the potential to reduce TB-related mortality even further in people living with HIV.
ID CON: What else should infectious disease and public health specialists know about this novel test?
CD: A diagnostic test with potential to improve the management of TB in people living with HIV is a major advancement for a large underserved patient population. While the assay’s increased diagnostic sensitivity is ground breaking, the findings need to be confirmed in prospective studies. These are currently in late-stage planning and will be starting over the coming months. Furthermore, the considerations for implementation are assessed in a qualitative study, as the test does have 2 more steps than the AlereLAM test, with one step being time sensitive.
ID CON: What is the next step in bringing this test into clinical practice? How might cost be a factor?
CD: As mentioned previously, several studies are planned to start over the coming months. These will inform a World Health Organization (WHO) policy review that is expected to take place in 2020. In parallel, the test is being transferred to large-scale manufacturing in preparation for commercial launch.
ID CON: What is your overall take-home message for infectious disease and public health specialists?
CD: There is huge potential for novel LAM-based tests to transform our ability to diagnose TB in people living with HIV. Additional research suggests that LAM as a biomarker also has potential in HIV-negative patients. Multiple ongoing developments, supported by FIND, the Bill & Melinda Gates Foundation, and others are harnessing the learnings from the development of the FujiLAM test into even more sensitive tests in the coming years. LAM tests have an important role to play in finding the “missing millions” and ending the TB epidemic.
Reference:
Broger T, Sossen B, du Toit E, et al. Novel lipoarabinomannan point-of-care tuberculosis test for people with HIV: a diagnostic accuracy study. Lancet Infect Dis. 2019;19(8):852-861. https://doi.org/10.1016/S1473-3099(19)30001-5.