| Paradoxical IRIS Criterion |
Alternative diagnosis (if criterion not met) |
| Prior diagnosis of cryptococcal infection |
Possible Unmasking Cryptococcal Infection |
| Documented clinical improvement after initiation of appropriate antifungal therapy and prior to suspected IRIS event |
Primary failure of antifungal therapy |
| Receiving antiretroviral therapy (ART) |
Progression of cryptococcosis due to ongoing immunosuppression |
| Virologic response with >1 log10 copies/mL decrease in HIV RNA (optional to verify if compliant with ART) |
Progression of cryptococcosis due to ongoing immunosuppression, or
No suitable specimen available for exclusion of virologic failure |
Clinical deterioration with an inflammatory condition
(e.g. meningitis, cryptococcomas, pneumonitis, lymphadenopathy, or cutaneous / soft tissue lesions) |
Consider alternative pathogens and/or non-inflammatory pathology |
| Negative cryptococcal culture |
True culture-positive relapse of cryptococcosis during treatment |
| Investigations negative for bacterial and mycobacterial infection |
Other opportunistic infection |
| Significant ART or antifungal non-adherence |
Relapse of cryptococcosis due to non-adherence to therapy |
