Dr. Tihana Bicanic of the University of Cape Town, South Africa, and team explained that once ART is in process, enhanced cell-mediated immune responses can lead to unmasking of latent (cryptococcal) infection or recurrence of symptoms and signs of previously identified and treated infection in up to 30% of cases, with serious consequences.

In two studies of antifungal therapy for HIV-associated cryptococcal meningitis, the researchers enrolled 118 patients in 2005 and 2006. The 65 patients who later started on ART were then monitored to identify incidence, characteristics, risk factors, and outcomes of CM-IRIS.

The study investigators reported that 11 patients (17%) developed CM-IRIS at a median 29 days after starting ART. Risk of CM-IRIS in patients were not predicted by any features of the first CM episode (fungal burden, clearance rate, CSF or HIV parameters).

Patients with CM-IRIS had greater increases in CD4 cell counts from baseline (p=0.01), at 6 months after the start of therapy. But there was no difference between first CM and CM-IRIS episodes in levels of interferon gamma, tumor necrosis factor alpha, or interleukin 6.

Patients with CM-IRIS had greater immune restoration in response to ART, the authors conclude. They call for larger studies to explore the immunological basis of IRIS, to help identify high-risk patients, and to guide management.