One-week treatment with amphotericin B deoxycholate (AmBd)– and flucytosine (5FC)–based therapy, followed by fluconazole (FLU) on days 8 through 14, is probably superior to other regimens for treatment of HIV-associated cryptococcal meningitis, according to the authors of a review of the available literature in the Cochrane Database of Systemic Reviews.
CDC/Dr. Leanor Haley
Cryptococcus neoformans is the most common cause of cryptococcal meningitis in patients with HIV.
The review is an update of one previous previously published in 2011. The authors found 13 eligible studies that enrolled 2,426 participants and compared 21 interventions. They performed a network meta-analysis using multivariate meta-regression, modeled treatment differences (RR and 95% confidence interval), and determined treatment rankings for 2-week and 10-week mortality outcomes using surface under the cumulative ranking curve, which represents the probability that a treatment will present the best outcome with no uncertainty and was used to develop a hierarchy of treatments for HIV-associated cryptococcal meningitis.
In addition, certainty of the evidence was assessed using the GRADE approach, according to Mark W. Tenforde, MD, of the University of Washington School of Public Health, Seattle, and his colleagues.
They found “reduced 10-week mortality with shortened [AmBd and 5FC] induction therapy, compared to the current gold standard of 2 weeks of AmBd and 5FC, based on moderate-certainty evidence.” They also found no mortality benefit of combination 2 weeks AmBd and FLU, compared with AmBd alone.
“In resource-limited settings, 1-week AmBd- and 5FC-based therapy is probably superior to other regimens for treatment of HIV-associated cryptococcal meningitis,” they wrote. “An all-oral regimen of 2 weeks 5FC and FLU may be an alternative in settings where AmBd is unavailable or intravenous therapy cannot be safely administered.” These results indicated the need to expand access to 5FC in resource-limited settings in which HIV-associated cryptococcal meningitis is most common.
They also reported finding no mortality benefit of 2 weeks of combination AmBd and FLU, compared with AmBd alone.
“Given 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,” Dr. Tenforde and his colleagues stated.
The authors reported that they had no relevant conflicts of interest.
SOURCE: Tenforde MW et al. Treatment for HIV-associated cryptococcal meningitis. Cochrane Database Syst Rev. 2018 Jul 25;7:CD005647. doi: 10.1002/14651858.CD005647.