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Biomarker levels associated with IRIS in patients with HIV, TB
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Patients with advanced HIV and tuberculosis who experience tuberculosis-associated immune reconstitution inflammatory syndrome or early death had distinct levels of inflammatory biomarkers before and after initiating ART, according to researchers from the University of Pennsylvania.
“Our findings urge caution in treatment of patients with advanced HIV and tuberculosis as a homogeneous group,” the researchers wrote in The Lancet Infectious Diseases. “The somewhat inverse association between pre-ART cytokine concentrations in patients with tuberculosis-associated [immune reconstitution inflammatory syndrome (IRIS)] and early mortality, and the contrasting degrees of CD4 cell recovery, suggests that interventions that seek to prevent tuberculosis-associated IRIS could inadvertently increase risk of death.”
Shruthi Ravimohan, PhD, and colleagues with the Botswana-UPenn Partnership, conducted a prospective cohort study that enrolled 201 ART-naive adults with advanced HIV and pulmonary TB in Botswana from Nov. 12, 2009, to July 3, 2013. The researchers obtained clinical data at baseline and then monthly, and also evaluated blood samples taken at baseline and after 4 weeks of ART to measure levels of 29 inflammatory biomarkers. The patients were followed for 6 months.
Shruthi Ravimohan
The final analysis included 170 patients, of which 19% developed TB-associated IRIS (median time, 28 days) after ART initiation and 11% died (median time, 81 days). In adjusted models, lower concentrations of eight biomarkers pre-ART were associated with TB-associated IRIS: granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-2, IL-6, IL-15, IL-12p40, IL-12p70, IL-3 and IL-17a. The investigators observed that higher concentrations of tumor necrosis factor (TNF)-alpha and monocyte chemoattractant protein (MCP)-1 pre-ART were associated with increased risk for death.
In adjusted models, increased concentrations of IL-6, TNF-alpha, IL-6 and G-CSF after 4 weeks of ART were associated with TB-associated IRIS. The researchers also found associations between increased concentrations of G-CSF, IL-3, IL-12p40, IL-15 and IL-1RA at week 4 of ART and death.
“Taken together, these findings have several implications for future research and clinical care,” the researchers wrote. “Several randomized trials are presently assessing or have recently investigated immunomodulatory therapies at the time of ART initiation in patients with advanced HIV and tuberculosis as a way to prevent tuberculosis-associated IRIS. Our data suggest that immunomodulatory therapies that inhibit inflammation without suppressing adaptive immune recovery should be prioritized.”
Disclosure: The researchers report no relevant financial disclosures.
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