Nearly a Fifth of AIDS-Related Deaths Attributed to Cryptococcal Meningitis

Although the expansion of antiretroviral therapy (ART) has likely contributed to a decrease in the global burden of HIV-associated cryptococcal meningitis, cryptococcosis accounts for 19% of AIDS-related deaths worldwide. These study findings were published in The Lancet Infectious Diseases.

The prevalence of advanced HIV infection was estimated using data captured from 2019 to 2020 and population-based HIV impact assessment surveys from 2016 to 2018. A literature review was used to estimate the prevalence of cryptococcal antigenemia among individuals with advanced HIV infection, defined as a CD4 cell count of at least 200 cells/uL. Published literature was also reviewed to estimate the rate of progression from cryptococcal antigenemia to meningitis and death.

In 2020, an estimated 36.7 million adults were living with HIV infection worldwide, of whom 23.8 million resided in sub-Saharan Africa, and 27.5 million were receiving ART. An estimated 4.3 million (12%) adults with HIV infection had advanced disease,, of whom 58% resided in sub-Saharan Africa.

Studies were reviewed for data about cryptococcal antigen positivity rates in sub-Saharan Africa (n=53), Asia (n=10), Latin America (n=10), the Middle East (n=2), Europe (n=1), and North America (n=1). The global rate of cryptococcal antigenemia was found to be 4.4% (95% CI, 1.6%-7.4%) among individuals with advanced HIV infection.

Among the estimated 179,000 CrAg-positive individuals with advanced HIV infection, an estimated 152,000 developed cryptococcal meningitis and 112,000 died from cryptococcal meningitis. This number of deaths accounted for 19% of all AIDS-related deaths.

Stratified by region, the rate of AIDS-related deaths associated with cryptococcal meningitis was highest in eastern Europe and central Asia (23%), followed by eastern and southern Africa (21%), Asia and the Pacific (20%), eastern Europe and central Asia (19%), the Caribbean (19%), western and central Africa (15%), western central Europe and North America (8%), and the Middle East and north Africa (3%).

The researchers estimated that if all regions implemented a national cryptococcal antigen screening program that evaluated at least 80% of individuals entering or reentering HIV care, and if preemptive fluconazole therapy was distributed, an estimated 34000 cryptococcal meningitis diagnoses (22%) would be avoided. In addition, a global screening program was estimated to save 21000 lives annually, or 19% of cryptococcal-related deaths.

This study was limited by several unknowns, such as the number of people living with HIV infection who are unaware of their advanced disease status.

According to the researchers, “The persistent burden of infection suggests that death from cyptococcal infection remains a marker for failure in the HIV cascade of care.”