Cryptococcus neoformans infection in a cohort of Italian AIDS patients: Natural history, early prognostic parameters, and autopsy findings

This observational cohort study of 4,160 AIDS patients hospitalised in a si ngle institution in northern Italy between January 1985 and December 1999 w as carried out in order to assess the natural history of cryptococcosis, th e epidemiological trend of this opportunistic infection, the risk factors p redictive of death at 10 weeks, the response to therapy, and autopsy findin gs. Cryptococcosis was diagnosed in 177 (4.2%) patients and was the AIDS-de fining disease in 2.8% of cases. Its prevalence decreased significantly ove r time (from 6.4% in the period 1985-1989 to 5.7% in 1990-1993, 3.1% in 199 4-1996, and 1.9% in 1997-1999, P <0.0001). Although neurologic disease was the most frequent clinical picture, a significant proportion of the patient s (24.2%) presented with extraneural cryptococcosis. In a Cox multivariate analysis, high titres of cerebrospinal fluid antigen (> 5000) and drug addi ction were predictive of death at 10 weeks. A complete clinical and mycolog ical response was achieved in 60.8% of the treated patients, with the highe st response rate being observed in those treated with amphotericin plus flu cytosine (66.6%). Cryptococcosis relapsed in 12.8% of patients on secondary prophylaxis. Autopsy findings demonstrated that cryptococcosis is a dissem inated disease, but long-term antifungal treatment may be able to eradicate it in a subgroup of patients.