Different presentations and outcomes between HIV-infected and HIV-uninfected patients with Cryptococcal meningitis

Abstract

Cryptococcus species are the most common causative agents of fungal meningitis. Different populations may show different clinical manifestations and outcomes. In this retrospective study, we investigated these differences in patients with and without HIV infection. From 1995 to 2009, we collected data from HIV-infected or HIV-uninfected patients aged 18 years or over who had cryptococcal meningitis (CM) in a medical center in Taiwan. We reviewed and analyzed their demographic data, clinical manifestations, therapeutic strategies and outcomes. Among the 72 patients with CM, 19 HIV-infected patients were predominantly younger males, and all of them had AIDS status when CM was diagnosed. In contrast, the 53 HIV-uninfected patients were mostly older males with underlying diseases. The time from initial symptoms to diagnosis was shorter in HIV-infected patients (median 10 vs. 18 days, p=0.048). The HIV-infected patients presented with less pleocytosis (p=0.003) and lower protein levels in the cerebrospinal fluid (CSF), but a higher proportion had positive results for cryptococci in the CSF (90% vs. 60%, p=0.02) and blood (53% vs. 21%, p=0.009) cultures. Surgical drains and repeated lumbar punctures for the management of increased intracranial pressure were performed in 47% of the HIV-infected patients and 38% of the HIV-uninfected patients. A lower mortality rate was observed in the HIV-infected patients (p=0.038). On multivariate analysis, initial CD4 count ≤20/mm(3) was an indicator of death or relapse in HIV-infected patients. In the HIV-uninfected group, the initial high cryptococcal antigen titer in the CSF (≥1:512) and hydrocephalus were related to unsatisfactory outcomes. In addition to well-known differences, we found a lower mortality in HIV-infected patients than in HIV-uninfected patients. Cryptococci and inflammation in the central nervous system may play important roles in the pathogenesis of CM. Low intensity of inflammation and effective surgical CSF drains for increased intracranial pressure and cryptococci removal may contribute to lower mortality in HIV-infected patients.