Publications & Reports

Cryptococcosis-IRIS is associated with lower Cryptococcus-specific IFN-gamma responses before antiretroviral therapy but not higher T-cell responses during therapy.

Chang CC, Lim A, Omarjee S, Levitz SM, Gosnell BI, Spelman T, Elliott JH, Carr WH, Moosa MY, Ndung'u T, Lewin SR, French MA
Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne 3000, Australia.


Background. Cryptococcosis-associated immune reconstitution inflammatory syndrome (C-IRIS) may be driven by aberrant T-cell responses to cryptococcal antigens. We investigated this in HIV-infected patients with treated cryptococcal meningitis (CM) who commenced combination antiretroviral therapy (cART).Methods. Mitogen- and cryptococcal mannoprotein (CMP)-activated (CD25+CD134+) CD4+ T-cells and induced production of IFN-gamma, IL-10 and CXCL10 were assessed in whole blood cultures, in a prospective study of 106 HIV-CM co-infected patients.Results. Patients with paradoxical C-IRIS (n=27), compared to patients with no neurological deterioration (no-ND; n=63), had lower CMP-induced IFN-gamma production in 24-hour cultures of blood collected pre-cART and 4-weeks post-cART (p=0.0437 and 0.0257, respectively) and lower CMP-activated CD4+ T-cell counts pre-cART (p=0.0178). Patients who survived to 24-weeks had higher proportions of mitogen-activated CD4+ T-cells and higher CMP-induced CXCL10 and IL-10 production in 24-hour cultures pre-cART than patients who did not survive (p=0.0053, 0.0436 and 0.0319, respectively). C-IRIS was not associated with higher CMP-specific T-cell responses before or during cART.Conclusion. Greater preservation of T-cell function and higher CMP-induced IL-10 and CXCL10 production before cART are associated with improved survival on cART. Lower CMP-induced IFN-gamma production pre-cART but not higher CMP-specific T-cell responses after cART were risk factors for C-IRIS.


  • Journal: The Journal of Infectious Diseases
  • Published: 12/06/2013
  • Volume: 208
  • Issue: 6
  • Pagination: 898-906


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