Treatment for HIV-associated cryptococcal meningitis.

Area of Science:

• Infectious Diseases
• Mycology
• Public Health

Background:

• Cryptococcal meningitis is a severe fungal infection, a leading cause of HIV-related mortality globally.
• Optimal induction therapy remains unclear, especially in resource-limited settings facing challenges with potent antifungal drug toxicities.

Purpose of the Study:

• To evaluate the most effective induction therapy for reducing mortality in HIV-associated cryptococcal meningitis.
• To compare the side effect profiles of various antifungal induction therapies.

Main Methods:

• A systematic review and network meta-analysis of randomized controlled trials (RCTs) comparing antifungal induction therapies for HIV-associated cryptococcal meningitis.
• Searched multiple databases and clinical trial registries for eligible studies published up to July 2018.
• Assessed outcomes including mortality, cerebrospinal fluid fungal clearance, and adverse events, using random-effects models and GRADE approach for evidence certainty.

Main Results:

• Thirteen RCTs with 2426 participants compared 21 interventions.
• A one-week regimen of amphotericin B deoxycholate (AmBd) and flucytosine (5FC), followed by fluconazole (FLU), showed lower 10-week mortality compared to several other regimens.
• This shortened AmBd and 5FC regimen demonstrated similar fungal clearance and lower rates of severe anemia compared to a two-week AmBd and 5FC regimen.

Conclusions:

• One-week AmBd- and 5FC-based therapy is likely superior for HIV-associated cryptococcal meningitis in resource-limited settings.
• An all-oral regimen of two weeks of 5FC and FLU may be an alternative when AmBd is unavailable.
• Limited data exist for pediatric populations and high-income countries, requiring further research.