• Tihana Bicanic, Graeme Meintjes, Kevin Rebe, Anthony Williams, Angela Loyse, Robin Wood, Madeleine Hayes, Shabbar Jaffar, and Thomas Harrison.
• Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa. tihana@never.com
• J. Acquir. Immune Defic. Syndr. 2009 Jun 1; 51 (2): 130-4.

BackgroundProspective data on incidence, characteristics, and risk factors for cryptococcal meningitis immune reconstitution inflammatory syndrome (CM-IRIS) are lacking.MethodsProspective study of 65 antiretroviral therapy (ART)-naive HIV-infected cryptococcal meningitis (CM) patients, who started ART after initiation of antifungal treatment. CM-IRIS definition: (1) cerebrospinal fluid (CSF) culture-confirmed CM, (2) symptom resolution before starting ART, (3) adherence to fluconazole and ART, (4) recurrence of CM symptoms after starting ART, (5) immunologic and/or virologic response to ART, (6) no alternative diagnosis.ResultsART was started at a median of 47 days from CM diagnosis. CM-IRIS developed in 11 of 65 (17%), at a median 29 days from starting ART. No factors at first CM episode (fungal burden, rate of clearance, CSF, or HIV parameters) predicted those at risk of CM-IRIS. At 6 months on ART, IRIS patients had greater CD4 rise from baseline (220 vs. 124 x 10 cells /L in non-IRIS, P = 0.01), and 4 of 11 CM-IRIS patients died compared with 14 of 54 non-IRIS patients (P = 0.5). For those developing CM-IRIS, CSF proinflammatory cytokines interferon gamma, tumour necrosis factor alpha, and interleukin 6, did not differ between first CM and CM-IRIS episode.ConclusionsPatients with CM-IRIS had greater immune restoration in response to ART. Although common and potentially fatal, larger prospective studies are needed to determine whether CM-IRIS, in patients treated initially with amphotericin B, is associated with any increase in overall mortality.

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