When resources are limited, one week of combined amphotericin B deoxycholate and flucytosine may be the best choice for reducing the risk of death from cryptococcal meningitis in HIV-positive individuals, according to a new Cochrane Review.

"Cryptococcal meningitis is a severe fungal infection that occurs primarily in the setting of advanced immunodeficiency and remains a major cause of HIV-related deaths worldwide," the reviewers explain.

HIV-associated cryptococcal meningitis

"The best induction therapy to reduce mortality from HIV-associated cryptococcal meningitis is unclear, particularly in resource-limited settings where management of drug-related toxicities associated with more potent antifungal drugs is a challenge."

Dr. Mark Tenforde of the University of Washington in Seattle and colleagues reviewed 13 studies that enrolled 2,426 people and compared 21 different therapies. All studies were carried out in adults, and all but two studies were conducted in resource-limited settings, including 11 of 12 studies with 10-week mortality data.

Based on their review, the researchers conclude that shorter initial treatment with one week of combined amphotericin B deoxycholate and flucytosine "probably results in lower risk of death than longer treatment with two weeks of combination amphotericin B deoxycholate and flucytosine that has traditionally been recommended in treatment guidelines."

"Previous guidelines," they explain, "have recommended two weeks of combination intravenous amphotericin B and oral flucytosine as the best available treatment. However, due to the high cost of treatment and limited availability of these potent antifungal drugs as well as challenges in managing common drug toxicities, resource-limited countries often use less effective therapies such as oral fluconazole alone."

Treatment Options 

"The shorter treatment," they add, "likely results in similar clearance of the infection with less toxicity from the drugs used for treatment. Where amphotericin B deoxycholate cannot be given, two weeks of combined flucytosine with fluconazole is likely a good treatment option."

Dr. Tenforde and colleagues note, however, that due to the absence of data from studies in children, and limited data from high-income countries, "our findings provide limited guidance for treatment in these patients and settings."