Immune reconstitution inflammatory syndrome in HIV-associated cryptococcal meningitis: a prospective study.
BACKGROUND
Prospective data on incidence, characteristics, and risk factors for cryptococcal meningitis immune reconstitution inflammatory syndrome (CM-IRIS) are lacking.


METHODS
Prospective 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.


RESULTS
ART 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.


CONCLUSIONS
Patients 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.
Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa. tihana@never.com
Tihana
T
Bicanic
Graeme
G
Meintjes
Kevin
K
Rebe
Anthony
A
Williams
Angela
A
Loyse
Robin
R
Wood
Madeleine
M
Hayes
Shabbar
S
Jaffar
Thomas
T
Harrison
D017088:AIDS-Related Opportunistic Infections / Q000150:complications* / Q000188:drug therapy; D019380:Anti-HIV Agents / Q000627:therapeutic use; D000935:Antifungal Agents / Q000627:therapeutic use; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000150:complications* / Q000453:epidemiology; D015994:Incidence; D016919:Meningitis, Cryptococcal / Q000150:complications* / Q000188:drug therapy; D011446:Prospective Studies; D012307:Risk Factors
D019380:Anti-HIV Agents; D000935:Antifungal Agents