Primary prevention

Cryptococcal polysaccharide antigen (CrAg) screening and pre-emptive antifungal therapy for people who are CrAg positive improves survival and reduces development of invasive cryptococcal disease.[30] This has been most rigorously studied in the REMSTART trial, which randomised 2000 individuals with HIV infection and CD4 count <200 cells/mm³ to either standard care or standard care plus CrAg screening and adherence counselling.[31] The trial noted a 28% relative reduction in mortality for patients who received CrAg screening and adherence counselling.

The World Health Organization (WHO) and other international guidelines recommend screening all adults and adolescents with HIV infection and a CD4 count <100 cells/mm³ before initiating or reinitiating antiretroviral therapy.[23][32]​​ CrAg screening may also be considered at a higher CD4 count threshold of <200 cells/microlitre.[23] Those who are CrAg positive, without signs or symptoms of meningitis, should be given pre-emptive antifungal therapy (fluconazole, given as induction, consolidation, and maintenance regimens). This screening and pre-emptive treatment strategy is cost-effective, because it averts expensive, extended hospitalisations for fulminant meningitis, where mortality remains high.[33]

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/mm³ (may also be considered at a higher CD4 count threshold of <200 cells/microlitre).[23]

In the US, routine serum CrAg screening is recommended for people meeting the following criteria:[20]

  • New diagnosis of HIV, and

  • No overt clinical signs of meningitis, and

  • CD4 count ≤100 cells/mm³.

People with a positive screening test should undergo cerebrospinal fluid evaluation for central nervous system infection.[20]

Secondary prevention

Secondary prophylaxis of cryptococcosis involves chronic maintenance therapy with fluconazole as first choice to prevent recurrence of the infection.[20][83]​ This may be discontinued in patients who respond to antiretroviral treatment (ART; i.e., CD4 cell counts ≥100 cells/mm³, 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/mm³.[20]

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