Optimizing antifungal therapy for HIV-associated cryptococcal meningitis in Africa

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We will test the activity of alternative doses and combinations of antifungal drugs in the treatment of cryptococcal meningitis in Africa. Cryptococcal meningitis is a very common infection and cause of death in patients with HIV and AIDS in Africa. Current drug treatment takes a long time to control the infection. In addition, improvements in treatment have been slow because traditional trials of treatment need many patients and are therefore slow and expensive to undertake. However, we have now developed a new way to test the activity of new drug combinations and dosages in small numbers of patients, by measuring the rate of killing of the organism causing the infection. Using this method, we will test alternative drug combinations and dosages in patients that laboratory testing and animal experiments have suggested will be more active and also safe. Parallel studies will be done: to optimize doses and combinations with the intravenous drug, amphotericin B, and with the oral drug, fluconazole. The results of the studies will be used to determine how best to use the drugs that are currently available, and to select the best combinations for further trials to find out if the new combinations can reduce the number of deaths caused by this infection.