Markers of CD4-cell activation became elevated in patients who had TB immune reconstitution inflammatory syndrome (IRIS) after they began antiretroviral therapy (ART) for the first time. The ANRS 129 BKVIR team believes their findings “support a role for CD4+ T-cell activation prior to massive inflammation in the development of TB-IRIS.”
People starting ART with Mycobacterium tuberculosis may experience paradoxical worsening to TB symptoms, called IRIS. TB-IRIS may cause significant morbidity and must be distinguished from TB recurrence resulting from failing treatment.
ANRS investigators conducted this single-arm multicenter trial to see whether changes in inflammatory biomarkers could predict TB-IRIS. They monitored 26 plasma biomarkers through the first 24 weeks of ART in people being treated for TB and starting their first antiretroviral regimen.
TB-IRIS developed in 23 of 69 people (33%). Inflammatory cytokines and chemokines interleukin (IL)-6, IL-8, interferon-gamma-induced protein 10 (IP-10), and tumor necrosis factor-alpha (TNF-α) all rose significantly at ART week 4 in people with IRIS (P < 0.05 for each marker).
Levels of the soluble IL-2 receptor sCD25, released upon CD4-cell activation, was significantly higher at week 0 in IRIS patients than in patients without IRIS (P < 0.05). sCD25 levels remained elevated in IRIS patients throughout follow-up.
IL-7, a cytokine related to CD4-cell homeostasis, tended to be higher in IRIS patients than non-IRIS patients. Higher baseline levels of sCD25 and IL-7 each independently predicted a shorter time to TB-IRIS (P = 0.005 and P = 0.02).
Source: Lisa A. Chakrabarti, Céline Boucherie, Florence Bugault, Marie-Christine Cumont, Caroline Roussillon, Guillaume Breton, Olivier Patey, Geneviève Chêne, Laura Richert, Olivier Lortholary. Biomarkers of CD4+ T-cell activation as risk factors for tuberculosis-associated immune reconstitution inflammatory syndrome. AIDS. 2014; 28: 1593-1602.
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Source: IAS