Emerging concepts in HIV-associated cryptococcal meningitis

Abstract

Purpose of review: HIV-associated cryptococcal meningitis remains a significant contributor to AIDS-related mortality despite widened access to antiretroviral therapy. Even in clinical trial settings 10-week mortality is roughly 40%. A number of important clinical trials have either recently concluded or are actively recruiting.

Recent findings: Global burden of disease estimates suggest cryptococcal meningitis causes 181 100 deaths annually. Screening blood for cryptococcal antigen in HIV-infected individuals with CD4 cell counts less than 100 cells/μl and preemptive antifungal treatment for those with detectable cryptococcal antigen reduces the incidence of cryptococcal meningitis and is likely to reduce mortality. Cryptococcal meningitis treatment with conventional 14-day courses of amphotericin are associated with high toxicity and mortality and can be reduced to 7 days if given alongside flucytosine. Flucytosine is a significantly superior adjunct to amphotericin treatment compared with fluconazole. In settings without amphotericin B dual oral antifungal combinations of flucytosine and fluconazole offer an effective alternative treatment. A single, high-dose of liposomal amphotericin is effective at reducing fungal burden and is being tested in a phase III trial.

Summary: Recently completed and ongoing clinical trials are increasing our understanding of how to optimize induction therapy for cryptococcal meningitis. Advocacy efforts are needed to broaden access to amphotericin formulations and flucytosine.