Study Evaluating Efficiency and Tolerance of High-dose Fluconazole Associated With Flucytosine as Induction Therapy for Cryptococcal Meningitis Associated With HIV in Sub-saharan Africa

Prospective Pilot Study to Evaluate a Standardized Management of Cryptococcal Meningitis in Patients Infected With HIV in Sub-Saharan Africa Involving an Initial Combination Therapy With Fluconazole and Flucytosine in High Doses, Complemented by Repeat Lumbar Punctures

The aim of the trial is to demonstrate that in a sub-Saharan African setting, the association of:

1. Oral treatment : high dose of fluconazole (1600mg/d) associated with flucytosine (100 mg/kg/j) as induction therapy
2. lumbar punctures to control intracranial pressure

can decrease mortality rate below 35% at 10 weeks.

This is a non-randomized open label pilot study, with standardized management of cryptococcoses meningitis and follow-up in Burundi and Ivory Coast. A total of 41 patients will be enrolled.

Inclusion Criteria:

• > 18 years
• HIV Infection
• First episode of cryptococcal meningitis on basis CSF India ink and/or CSF cryptococcal antigen.
• Glasgow > 9 after lumbar punctures
• Absence of peripheral focal deficit in the limbs
• informed consent signed

Exclusion Criteria:

• Hemoglobin <7.5 g / dl;
• neutrophils count <500/mm3;
• Platelets count <50 000/mm3;
• transaminases > 5 times upper limit of normal;
• Troubles with severe mental alertness Glasgow <9 after the initial lumbar puncture;
• focal neurological deficit in the limbs;
• Pregnancy or lactation on going;
• Ongoing systemic antifungal treatment;
• History of cryptococcal meningitis;
• Ongoing rifampicin and ritonavir treatment;
• Subject participating in another study with a risk of mutual interference on the interpretation of results.