Emerging concepts in HIV-associated cryptococcal meningitis

Abstract

Purpose of review: HIV-associated cryptococcal meningitis (CM) 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 etimates suggest CM causes 181,100 deaths annualy. Screening blood for cryptococcal antigen (CrAg) in HIV-infected individuals with CD4 cell counts <100 cells/µL and pre-emptive antifungal treatment for those with detectable CrAg reduces the incidence of CM and is likely to reduce mortality. CM treatment with conventional 14-day courses of amphotericin are associated with high toxicity and mortality and can be reduced to seven days if given alongside flucytosine. Flucytosine is a significantly superior adjunct to amphotericin treatment compared to 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 optimise induction therapy for CM. Advocacy efforts are needed to broaden access to amphotericin formulations and flucytosine.

Clinical mycology in Latin America and the Caribbean: A snapshot of diagnostic and therapeutic capabilities

“…One‐quarter of the institutions surveyed reported no access to CrAg ® . Considering the HIV epidemic in Latin America and the Caribbean, this could be leading to significant mortality—by having a delayed or even an unreliable diagnosis, taking into account that cryptococcal meningoencephalitis is a major contributor to mortality in people living with HIV . The situation gets even worse when we track the availability of 5‐FC.…”

“…Considering the HIV epidemic in Latin America and the Caribbean, 16 this could be leading to significant mortality-by having a delayed or even an unreliable diagnosis, taking into account that cryptococcal meningoencephalitis is a major contributor to mortality in people living with HIV. 17,18 The situation gets even worse when we track the availability of 5-FC. 5-FC is an extremely important drug to treat cryptococcosis: it significantly reduces mortality when added to amphotericin B, 19 and it proved to be effective in an "all-oral" regimen added to fluconazole.…”

Cryptococcal antigenemia and its predictors among HIV infected patients in resource limited settings: a systematic review

“…Cryptococcosis is one of the most important opportunistic infections among people living with advanced AIDS having defective cellular immune component and is a major contributor to AIDS-related mortality worldwide [2]. In spite of the increasing availability of antiretroviral treatment (ART), cryptococcal disease continues to be a leading cause of death among HIV infected patients in the developing world [3][4][5]. Considerable number of HIV-infected population still presents late to care with advanced AIDS [6,7].…”

Cryptococcal antigenemia and its predictors among HIV infected patients in resource limited settings: a systematic review

“…Although the infection begins in the lungs, certainly the most common presentation of cryptococcal disease, representing 70-90% of HIV-related cryptococcal disease, is cryptococcal meningitis (CM), which accounts for 15%-20% of all AIDS-related deaths globally, three quarters of which are in sub-Saharan Africa. Coupled with loose adherence to ART and retention in HIV care an estimated 223, 100 cases of CM resulted in 181, 100 deaths among people living with HIV in 2014 [2,4,7,13,15]. Screening patients for subclinical cryptococcal infection at the time of entry into ART programs using point-of-care tools like, cryptococcal antigen (CrAg) immunoassays is highly effective in identifying patients at risk of developing CM, allowing these patients to then be targeted with pre-emptive antifungal therapy to prevent the development of severe disease and mortality [16].…”