Benefits Associated With Primary Antifungal Prophylaxis for Cryptococcal Disease in HIV

Cryptococcus Neoformans
Cryptococcus Neoformans
Patients at risk for cryptococcal disease development can be treated with antifungal prophylaxis when cryptococcal antigen screening is not possible.

The risk for cryptococcal disease can be reduced by antifungal prophylaxis in individuals who are HIV-positive, according to a study recently published in Cochrane Database of Systematic Reviews. Patients at risk for cryptococcal disease development, including those who have low CD4 cell counts, can be treated with antifungal prophylaxis when cryptococcal antigen screening is not possible.

This systematic review included a total of 5426 participants in 9 trials, 6 of which included the administration of fluconazole and 3 of which administered itraconazole. Although the use of antifungal prophylaxis was not significantly associated with all-cause mortality (risk ratio [RR], 1.07; 95% CI, 0.80-1.43), it was associated with significant reductions in risk for cryptococcal disease (RR, 0.29; 95% CI, 0.17-0.49).

It was also significantly associated with reduced cryptococcal disease-related mortality (RR, 0.29; 95% CI, 0.11-0.72). In terms of tolerability, antifungal prophylaxis performed well and did not lead to more treatment discontinuation than did placebo (RR, 1.01; 95% CI, 0.91-1.13).

It also resulted in a similar degree of adverse events (RR, 1.07; 95% CI, 0.88-1.30) and serious adverse events (RR, 1.08; 95% CI, 0.83-1.41) when compared with standard care or placebo.

Individuals included in the studies were HIV-positive, had a low cluster of differentiation 4 cell counts, and did not have any history of cryptococcal disease. Articles were sourced from MEDLINE PubMed, CINAHL, EBSCOHost,, Conference on Retroviruses and Opportunistic Infections, CENTRAL, Embase OVID, WHO International Clinical Trials Registry Platform, and the International AIDS Society proceedings.

Bias and eligibility were reviewed independently by 2 authors. The study researchers used meta-analyses to pool data where needed and evaluated the quality of evidence with the GRADE approach.

Related Articles

The study researchers concluded, “[primary] prophylaxis with either fluconazole or itraconazole probably reduces the risk of developing cryptococcal disease. Prophylaxis also probably reduces the risk of death due to cryptococcal disease, however, this may not have translated to a reduction in all-cause mortality in the trials identified.”


Awotiwon AA, Johnson S, Rutherford GW, Meintjes G, Eshun-Wilson I. Primary antifungal prophylaxis for cryptococcal disease in HIV-positive people [published online August 29, 2018]. Cochrane Database Syst Rev. doi: 10.1002/14651858.CD004773.pub3