A study in this week's PLoS Medicine suggests that AIDS patients with cryptococcal meningitis who start HIV therapy are predisposed to immune reconstitution inflammatory syndrome (IRIS) -- an exaggerated inflammatory immune response that kills up to one-third of affected people -- if they have biomarkers (biochemicals) in their blood showing evidence of a damaged immune system that is not capable of clearing the fungal infection.
David Boulware and Paul Bohjanen from the University of Minnesota, Minneapolis, USA, and their colleagues, David Meya and Andrew Kambugu, at Makerere University in Kampala, Uganda enrolled 101 Ugandans with AIDS and recent cryptococcal meningitis who had not previously received HIV therapy and compared biomarker patterns in individuals who did and did not subsequently develop IRIS after starting HIV therapy. 45% of patients developed IRIS of whom 36% died, while only 21% of patients who did not develop IRIS died. Furthermore, the authors found that patients who later developed IRIS associated with cryptococcal meningitis after starting HIV therapy had 4-fold higher baseline concentrations of cryptococcal antigen and lower levels of several inflammatory cytokines in their blood compared to patients who did not develop CM-IRIS.
The authors say: "This study suggests that prediction of IRIS or death may be possible with measurement of pre-antiretroviral therapy serum biomarkers." They add, "Although requiring validation, these biomarkers might be an objective tool to stratify the risk of CM-IRIS and death, and could be used clinically to guide when to start antiretroviral therapy or use prophylactic interventions."
Funding: This work was supported by the University of Minnesota Academic Health Center (PRB, DBM), NIH National Institute of Allergy and Infectious Diseases (DRB: T32AI055433-03; L30AI066779; K12RR023247-04; K23AI073192. PRB: R03AI078750), Minnesota Medical Foundation (PRB, DRB, DBM), Tibotec REACH Initiative (PRB, DRB, DBM), University of Minnesota Dean's Grant-in-Aid (DRB), Academic Alliance Foundation (AK, DBM), Mucosal and Vaccine Research Program Colorado (ENJ), and the Veterans Affairs Research Service (ENJ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
Citation: Boulware DR, Meya DB, Bergemann TL, Wiesner DL, Rhein J, et al. (2010) Clinical Features and Serum Biomarkers in HIV Immune Reconstitution Inflammatory Syndrome after Cryptococcal Meningitis: A Prospective Cohort Study. PLoS Med 7(12): e1000384. doi:10.1371/journal.pmed.1000384
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