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.
Bicanic
Tihana
T
Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa. tihana@never.com
Meintjes
Graeme
G
Rebe
Kevin
K
Williams
Anthony
A
Loyse
Angela
A
Wood
Robin
R
Hayes
Madeleine
M
Jaffar
Shabbar
S
Harrison
Thomas
T
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