Blood test to detect active TB in people with HIV

A combination of plasma biomarkers might be used to detect prevalent active tuberculosis in people living with HIV. In a study published in Clinical Infectious Diseases, a team of researchers showed that biomarker levels differed in samples from HIV-infected people with and without active tuberculosis (TB) disease.

The team, from CIDRI-Africa, the University of Cape Town, the Western Cape Department of Health, Imperial College, and the Francis Crick Institute, 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).

The results illustrate that a combination of biomarkers is more likely to detect prevalent TB.

“This paper continues the valiant efforts to find a holy grail of TB rapid diagnostic and prognostic testing”, remarked one of the anonymous reviewers of the paper.

While the combination of biomarkers could unfortunately 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 (LTBI) 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 LTBI; 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 HIV[1].

Reference: Lesosky M, Rangaka MX, Pienaar C, Coussens AK, Goliath R, Mathee S, Mwansa-Kambafwile J, Maartens G, Wilkinson RJ, Wilkinson KA. Plasma biomarkers to detect prevalent, or predict progressive, HIV-1-associated tuberculosis. Clinical Infectious Diseases. (2018):cid/ciy823.