Clinical features of crytococcus neoformans infection in human immunodeficiency virus (HIV)-infected and HIV-uninfected patients

Background. Cryptococcosis in HIV-uninfected (HIV-) patients can occur in those with solid organ transplantation (SOT), malignancies, autoimmune disease, or no apparent underlying disease. Clinical features and disease manifestations of cryptococcosis in this population have been recognized to be distinct from that of HIV-infected (HIV+) patients. Methods. We conducted a retrospective chart review of all patients with cryptococcosis at a tertiary care hospital from January 2005 through March 2016. Clinical features, laboratory findings, and outcomes were reviewed. Variables were compared using Fisher's exact and Mann-Whitney U tests. Results. From 2005 and 2016, 98 patients were diagnosed with cryptococcosis, 35 (35.7%) of whom were HIV-. HIV-patients presented at an older age than HIV+ patients (median 59 versus 44; P < 0.0001) and were less likely to have headaches (28.6 versus 50.8%; P = 0.04). The central nervous system was the most commonly involved organ in both groups. HIV-patients had more involvement of lungs, skin, softtissue and osteoarticular sites than HIV+ patients. HIV+ patients were mostly not taking antiretroviral therapy (ART), had median CD4 count of 27, HIV RNA of 69,436 and had higher serum cryptococcal antigen titer than HIV-patients (median 768 versus 64, P = 0.0004). Among HIV-patients, 68.6% were on an immunosuppressant, 40% were SOT recipients, 22.9% had an autoimmune disease, 17.1% had malignancy, 11.4% had liver disease, 22.9% had a concomitant viral infection (cytomegalovirus, hepatitis C), and 5.7% had no identifiable condition. HIV-patients had a higher median cerebral spinal fluid (CSF) leukocyte count (31 versus 6, P = 0.08) and glucose (65 versus 51, P = 0.04) and were less likely to have a positive CSF culture. Mortality within 6 months of diagnosis was 9.5% in the HIV+ and 25.7% in the HIV-group (P = 0.04). Conclusion. The highest burden of cryptococcal disease continues to be in patients with HIV infection who are not taking ART. While low CD4 cell count and high HIV RNA portend risk in HIV+ patients, factors that identify at risk patients in this population are still not available. Similarly, there are no known markers of risk for HIV-patients, who are a more diverse population with more varied clinical presentations. Identification of new factors that govern development of cryptococcosis in HIV-and HIV+ patients are greatly needed.