Cryptococcal Meningitis and Clinical Outcomes in Persons with HIV: A Global View.

BACKGROUND

Cryptococcal meningitis (CM) is a major cause of morbidity and mortality in persons with HIV(PWH). Little is known about CM outcomes and availability of diagnostic and treatment modalities globally.

METHODS

This retrospective cohort study investigated CM incidence and all-cause mortality after CM diagnosis in PWH in the IeDEA cohort from 1996-2017. We estimated overall and region-specific incidence and incidence rate ratios using quasi-Poisson models adjusted for sex, age, calendar year, time-updated CD4, and time-updated antiretroviral therapy (ART) status. Mortality after CM diagnosis was examined using multivariable Cox models. A site survey from 2017 assessed availability of CM diagnostic and treatment modalities.

RESULTS

Among 518,852 PWH, there were 3,857 diagnosed cases of CM with an estimated incidence of 1.54 per 1000 person-years. Mortality over a median of 2.6 years of post-CM diagnosis follow-up was 31.6%, with 29% lost to follow-up. 2,478 (64%) were diagnosed with CM after ART start with a median of 253 days from ART start to CM diagnosis. Older age (HR 1.31 for 50 vs 35 years; 95%CI 1.12-1.53), lower CD4 (HR 1.15 for 200 vs 350 cells/mm3; 95%CI 1.03-1.30), and earlier year of CM diagnosis (HR 0.51 for 2015 vs 2000; 95%CI 0.37-0.70) were associated with higher mortality. Of 89 sites, 34% reported access to amphotericin B; 12% had access to flucytosine.

CONCLUSIONS

Mortality after CM diagnosis was high. A substantial portion of CM cases occurred after ART start, though incidence and mortality may be higher than reported due to ascertainment bias. Many sites lacked access to recommended CM treatment.