Primary prevention

Cryptococcal polysaccharide antigen (CrAg) screening and preemptive antifungal therapy for people who are CrAg positive improves survival and reduces development of invasive cryptococcal disease.[30][31][32][33][34]​​​​ This has been most rigorously studied in the REMSTART trial, which randomized 2000 individuals with HIV infection and CD4 count <200 cells/microliter to either standard care or standard care plus CrAg screening and adherence counseling.[31] The trial noted a 28% relative reduction in mortality for patients who received CrAg screening and adherence counseling.

The World Health Organization (WHO) and other international guidelines recommend screening all adults and adolescents with HIV infection and a CD4 count <100 cells/microliter before initiating or reinitiating antiretroviral therapy (ART).[23][35]​​​​​ US guidelines recommend routine surveillance testing for serum CrAg in people newly presenting to HIV care who have no overt clinical signs of meningitis and whose CD4 counts are ≤200 cells/microliter, and particularly in those with CD4 counts ≤50 cells/microliter.[20] People with a positive screening test should undergo cerebrospinal fluid evaluation for central nervous system infection.[20] Those who are CrAg positive, without signs or symptoms of meningitis, should be given preemptive antifungal therapy (fluconazole, given as induction, consolidation, and maintenance regimens).[20]

In settings where antigen screening is not available, the WHO recommends initiating fluconazole primary prophylaxis in people with HIV infection and a CD4 count <100 cells/microliter (may also be considered at a higher CD4 count threshold of <200 cells/microliter).[23]

Antifungal prophylaxis in the absence of a positive serum CrAg test is not recommended by US guidelines.[20]

Secondary prevention

Secondary prophylaxis of cryptococcosis involves chronic maintenance therapy with fluconazole as first choice to prevent recurrence of the infection.[20][91]​​​ This may be discontinued in patients who respond to ART (i.e., CD4 cell counts ≥100 cells/microliter, undetectable viral loads on ART, minimum of 1 year of azole antifungal chronic maintenance therapy after successful treatment of cryptococcosis).[20] Maintenance therapy should be reinitiated if the CD4 count decreases to <100 cells/microliter.[20]

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