Cryptococcal meningitis is a life-threatening opportunistic fungal infection in both HIV-infected and HIV-uninfected patients. According to the most recent taxonomy, the responsible fungus is classified into a complex that contains two species (Cryptococcus neoformans and C. gattii), with eight major molecular types. HIV infection is recognized worldwide as the main underlying disease responsible for the development of cryptococcal meningitis (accounting for 80–90% of cases). In several areas of sub-Saharan Africa with the highest HIV prevalence despite the recent expansion of antiretroviral (ARV) therapy programme, cryptococcal meningitis is the leading cause of community-acquired meningitis with a high mortality burden. Although cryptococcal meningitis should be considered a neglected disease, a large body of knowledge has been developed by several studies performed in recent years. This paper will focus especially on new clinical aspects such as immune reconstitution inflammatory syndrome, advances on management, and strategies for the prevention of clinical disease. 1. Introduction The encapsulated yeast, Cryptococcus spp., is a major cause of fungal meningitis and meningoencephalitis especially in immunocompromised patients [1, 2]. This basidiomycete fungus was first isolated in 1894 by Sanfelice in fruit juices and subsequently recovered from the tibial lesion of a patient by Busse and Buschke [3–5]. The genus has been named from the Greek words, kryptos (hidden) and kokkos (berry) but a long lists of names and synonyms have been generated until the adoption of the actual nomenclature [6]. However, although C. neoformans has been recognized for more than 100 years, the worldwide spread of HIV infection as well as the increasing number of patients with impaired immunity were responsible for the dramatic surge of this life-threatening infection only in the 80’s [7–9]. Although effective treatment for HIV disease has decreased significantly incidence of cryptococcal meningitis (CM) in western countries, it remains a common cause of infectious morbidity and mortality especially among HIV-positive patients living in sub-Saharan Africa and South-east Asia [10–16]. This paper will focus on main aspects of AIDS-associated cryptococcal meningitis with special attention on recent findings on immune reconstitution inflammatory syndrome, diagnosis, treatment, and prevention. Data were identified by searches on PubMed and Scopus using a combination of search terms including “cryptococcosis,” “AIDS,” “immune reconstitution inflammatory syndrome,” “cryptococcal
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