Antifungal combinations for treatment of cryptococcal meningitis in Africa

Researchers working on the ACTA clinical trial evaluated treatment interventions for cryptococcal meningitis in HIV populations, which is a challenge in sub-Saharan Africa.

Researchers working on the ACTA clinical trial evaluated treatment interventions for cryptococcal meningitis in HIV populations, which is a challenge in sub-Saharan Africa. The standard treatment of 2 weeks of amphotericin B plus flucytosine is mostly unavailable there, leaving countries to depend on donated or fluconazole induction monotherapy, which has a comparably inferior safety profile. Investigators assembled a sample of nearly 700 adult HIV patients with cryptococcal meningitis and randomized them to treatment with daily oral fluconazole plus flucytosine for 2 weeks, daily amphotericin B for 1 week, or amphotericin B for 2 weeks. Each of the patients in the amphotericin B groups was additionally randomized to fluconazole or flucytosine. After the induction treatment, all participants received fluconazole consolidation therapy. Based on 10-week mortality rates, 1 week of amphotericin B plus flucytosine is a viable alternative to 2 weeks of amphotericin B as induction therapy for cryptococcal meningitis in resource-limited settings. In the event that amphotericin B cannot be accessed or administered safely, the oral combination of fluconazole plus flucytosine for 2 weeks also presents an effective and sustainable option.