HIV-Associated Cryptococcal Meningitis: A Call for Action for New Treatment Options

Cryptococcal meningitis diagnosis at 62% is the leading cause of meningitis among adults with advanced HIV disease in areas with a high burden of infection. Despite attempts to improve treatment, in-hospital mortality remains unprecedentedly high. Disease complications associated with unmasking symptoms and relapse of fungal infections delay treatment and increase the risk of individuals succumbing to cryptococcal meningitis. In this narrative review, we highlight published clinical trials evaluating the treatment of HIV-associated cryptococcal meningitis with survival as the primary endpoint. Aggregated clinical trial data show a significant decrease in survival from diagnosis to 2 weeks of treatment, from 88.5% to 74% (p=0.001). The WHO standard of care was used as the control arm. Survival rates were similar between the control and trial arms. High in-hospital mortality remains a challenge for new survival-modifying treatments for cryptococcal meningitis. We provide evidence-based updates on cryptococcal meningitis treatment to inform new antifungal formulations or research approaches for improved outcomes. The consistency and generalizability of fungal clearance in the cerebrospinal fluid and the efficacy of antifungal drugs to clear fungi in the brain parenchyma remain unclear.