In a study published in Clinical Infectious Diseases, researchers have shown that biomarker levels differed in samples from HIV-infected people with and without active tuberculosis (TB). The findings suggest that a combination of plasma biomarkers might be used to detect prevalent active tuberculosis in people living with HIV.
The research team, from the Crick, CIDRI-Africa, the University of Cape Town, the Western Cape Department of Health and Imperial College, collaborated on an immuno-epidemiological study of stored blood samples taken from participants during a previous clinical trial conducted in South Africa.
Cross-sectional and longitudinal clinical data were available for evaluating plasma biomarkers for their ability to differentiate between prevalent active TB, incident TB (TB that developed during the study follow up) and controls (who did not develop TB during study follow up).
"Our results illustrate that a combination of biomarkers is more likely to detect prevalent TB," says Katalin Wilkinson, principal laboratory research scientist at the Crick, and corresponding author of the paper.
While the combination of biomarkers could not fully predict TB progression, this large prospective cohort study provides clinical utility by carefully describing the differences between these TB classifications.
Network and multivariable predictive analysis are suggestive of combinations of biomarkers that may demonstrate clinical significance. Thus, detecting prevalent TB with a combination of IFN-gamma and IL-2 is a potential advance that would be worth pursuing in a controlled future study. Additionally, the fact that unstimulated analytes were more likely to be helpful is also important, not only because they indicate underlying inflammatory processes leading to TB risk in the context of HIV-infection, but also because they would eliminate the need for antigen stimulation in a potential future blood test.
People living with HIV are offered isoniazid preventive therapy (IPT), to prevent development of active TB, along with antiretroviral therapy (ART). However, people with undetected active TB should not take IPT monotherapy because of the risk that Mycobacterium tuberculosis could develop drug resistance. Therefore, more accurate discrimination between prevalent active TB and latent TB infection before starting IPT is crucial, as fear of treating TB with IPT mono-therapy is a major barrier to IPT implementation. A new more sensitive diagnostic test for TB in HIV-positive people could help clinicians decide on the best course of treatment.
People living with HIV are particularly vulnerable to both new TB infection and progression of latent TB infection; TB is the leading cause of death in this population. In 2017, an estimated 322,000 South Africans developed new TB infections; 193,000 (60%) were also living with HIV. 78,000 South Africans with TB died, 72% of whom also had HIV1.