The ACTA Study

Improving Treatment for People with HIV and Cryptococcal Meningitis in Africa

research-context Context

Cryptococcal meningitis is a leading cause of death in HIV-infected patients in Africa, with mortality exceeding 50% at 10 weeks. It is estimated that cryptococcal meningitis is associated with over 100,000 deaths per year in sub-Saharan Africa.

The current recommended treatment for cryptococcal meningitis is 2 weeks of amphotericin B-based therapy, an antifungal drug. However, in many settings in Africa amphotericin B is not available or not used due to the requirements for in-hospital care, intravenous administration, close blood monitoring, and fluid and electrolyte supplements. These strenuous requirements are expensive and bring extra medical, nursing, and laboratory costs. Instead, many centres have relied on another anti-fungal drug called fluconazole; a safe and well-tolerated oral medication available free of charge through a donation programme. However, fluconazole alone is slow in controlling infection and is associated with high mortality.

In a small study, the combination of fluconazole with a second oral drug called flucytosine, another antifungal drug, has been shown to lead to faster control of infection, and to be associated with fewer deaths than fluconazole alone. In addition, a shorter 5-7 day course of amphotericin B has been shown to be much better tolerated than a 2 week course and reduces the need for intensive treatment monitoring, and potentially reduces the duration of hospitalisation.

research-aim Aim

The Advancing Cryptococcal meningitis Treatment for Africa (ACTA) randomised clinical trial will compare the following alternative strategies for the initial treatment of HIV-associated cryptococcal meningitis:

  1. Oral therapy: Fluconazole plus flucytosine
  2. Short course therapy: Amphotericin B for 7 days plus fluconazole or flucytosine
  3. 2 week therapy: Amphotericin B for 14 days plus fluconazole or flucytosine


research-timeline Timeline

October 2015 – October 2016

research-partnerships Partnerships

Funder: The Medical Research Council (UK) and ANRS (France) through St George’s, University of London
Trial Management Group: St George’s, University of London
Partners: Kamuzu Central Hospital / UNC Project and Queen Elizabeth Hospital / Malawi-Liverpool-Wellcome Trust, Malawi; University Teaching Hospital / IMReT, Lusaka, Zambia; Yaoundé Central Hospital and Douala General Hospital / ANRS, Cameroon; Muhimbili and Mwananymala hospitals / NIMR, Tanzania; Liverpool School of Tropical Medicine London School of Hygiene and Tropical Medicine.

research-team Study Team

Prof. Tom Harrison
Chief Investigator, St George’s University of London

Dr. Síle Molloy
Trial Manager, St George’s University of London

Dr. Adrienne Chan
Site – Principal Investigator, Dignitas International

Prof. Shabbar Jaffar
Co-Investigator, Liverpool School of Tropical Medicine

Prof. Duolao Wang
Statistician, Liverpool School of Tropical Medicine

Dr. Philip Bright
Study Physician, Dignitas International

research-info Contact

For more info, please email Dr. Adrienne Chan at

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