No survival benefit with fluconazole prophylaxis for cryptococcosis


In an observational Thai study of HV positive patients with less than 100 CD4 cells/μL who initiated antiretroviral therapy, the effect of prophylactic fluconazole was evaluated. All patients had a negative cryptococcal serum antigen test at inclusion and no history of previous cryptococcosis. A weekly dose of 400 mg of fluconazole was prescribed at the discretion of the attending physician. The primary endpoint was mortality and the secondary endpoint was diagnosis of cryptococcosis. The median baseline CD4 count was 26 in 201 patients who received prophylaxis and 35 in 101 patients who did not receive prophylaxis. One patient in each group died and there were 5 cases of cryptococcal infections in each group. After one and two years the overall median CD4 count had risen to 184 and 271 and 90.1 and 88.1 % had undetectable viral load after 1 and 2 years.

Sungkanuparph et al. Clin Infect Dis 2017;64:967-970

Comment: In this nonrandomized observational study in severely immunodeficient patients there was no survival benefit of fluconazole primary prophylaxis and no statistically significant difference in the number of cryptococcal infections between the two arms. There is no information in the paper on the number of patients who had positive cryptococcal serum antigen at baseline and thus were excluded from the study. Cryptococcal meningitis occurring soon after the initiation of antiretroviral therapy may be the result of “demasking” of a subclinical infection and therefore the importance of a negative cryptococcal serum antigen test should be stressed in severely immunodeficient patients who initiate antiretroviral therapy.