Abstract

Cryptococcal antigen (CrAg) is detectable in blood prior to the onset of symptomatic cryptococcal meningitis, a leading cause of death among people living with advanced HIV disease globally. Highly sensitive assays can detect CrAg in blood, and screening people living with HIV with low CD4 counts, followed by pre-emptive antifungal treatment, is recommended and widely implemented as part of a global strategy to prevent cryptococcal meningitis and end cryptococcal-related deaths. Cryptococcal antigenemia encompasses a spectrum of conditions from pre-clinical asymptomatic infection (CSF CrAg-negative), through subclinical (CSF CrAg-positive without overt meningism) to clinical symptomatic cryptococcal disease, usually manifesting as cryptococcal meningitis. This review summarizes current understanding of the pathophysiology, risk-factors for and clinical implications of cryptococcal antigenemia among people living with advanced HIV disease within this spectrum. It also provides an update on global prevalence, recommended screening and treatment strategies, and future considerations for improving outcomes among patients with cryptococcal antigenemia.