Prognosis

Mortality and morbidity

Unrecognized and untreated cryptococcosis can be fatal, especially in immunocompromised patients, and untreated cryptococcal meningoencephalitis is uniformly fatal. The estimated 1-year mortality for people with HIV-associated cryptococcal meningitis is 70% in low-income countries and 20% to 30% in high-income countries.[10][23]​​​ Outcomes in other immunosuppressed patients vary according to the underlying disease. Patients with idiopathic CD4 lymphopenia seem to have relatively favorable outcomes.[83] Early appropriate treatment reduces morbidity and prevents progression to potentially life-threatening central nervous system disease. The cryptococcal polysaccharide antigen (CrAg) status has been found to be an independent predictor of mortality in people with HIV.[64] Toxic adverse effects from antifungal therapy are common, and up to 30% of patients with cryptococcal meningitis and HIV develop immune reconstitution inflammatory syndrome (IRIS) following initiation or reinitiation of antiretroviral therapy (ART).[20][64][67]

Treatment failure and relapse

Treatment failure is defined as the lack of clinical improvement after 2 weeks of therapy (including management of increased intracranial pressure [ICP] with continued positive cultures) or relapse after initial clinical response (i.e., recurrence of symptoms with a positive cerebrospinal fluid [CSF] culture after ≥4 weeks of treatment).[20] Patients requiring suppressive therapy for more than 1-2 years are also considered treatment failures.[67]

In the absence of maintenance therapy, there is a high risk of relapse among people with HIV and cryptococcal meningitis who have been treated successfully. Positive CSF cultures after 2 weeks of therapy are predictive of future relapse and a less favorable clinical outcome.[1] Serum CrAg titers do not correlate with clinical improvement; however, pre-ART serum CrAg titers are predictive of future IRIS.[1][84][85]​​ If new clinical symptoms arise, a careful lumbar puncture should be performed to rule out the possibility of increased ICP or IRIS. The risk of recurrence seems to be low in people with HIV who have successfully completed a course of initial therapy, remain asymptomatic, and have a sustained increase (i.e., >6 months) in the CD4 count to ≥200 cells/microliter after potent ART.[1][9][11]

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