Rate of infection clearance may predict clinical outcome of HIV-associated cryptococcal meningitis

Further understanding the rate of cryptococcal meningitis infection clearance may be an effective means of exploring antifungal drug dosages and combinations, according to results of a multinational study.

The results also indicate that another barometer of antifungal drug dosages and combinations may be early fungicidal activity.

The aim of the study was to explore the clinical applicability of the hypothesis that the rate of infection clearance should be a clinically meaningful endpoint. The researchers wrote that understanding the relationships between factors that determine the outcome of cryptococcal meningitis infection may provide clues to strategies for intervention.

Data from four trials of initial antifungal therapy among people with HIV-associated cryptococcal meningitis were analyzed. In those trials, the rate of clearance of infection was determined and clinical and laboratory data had been gathered prospectively. The researchers explored the association between the rate of infection clearance and mortality.

There were 262 patients from South Africa, Thailand and Uganda involved in the study.

Clinical characteristics independently associated with increased mortality at two and 10 weeks included altered mental status at presentation, a high baseline organism load and a slow rate of clearance of infection. Multivariate analysis demonstrated that the associations between these factors and mortality were stronger at two weeks than at 10 weeks.

Antifungal drug regimen and baseline cerebrospinal fluid interferon levels were associated with infection clearance rate.

Bicanic T. Clin Infect Dis. 2009;49:702-709.