A large-scale clinical trial has demonstrated the efficacy of a new therapeutic protocol to treat cryptococcal meningitis associated with HIV infection and shown that it leads to fewer adverse effects.
An article published in the New England Journal of Medicine in March 2022 proposed an innovative treatment approach for cryptococcal meningitis. The new approach simplifies care for patients co-infected with HIV, the virus that causes AIDS, including in low-income countries. A treatment protocol combining several drugs (a single drip for intravenous administration of high dose liposomal amphotericin B, together with oral flucytosine and fluconazole) significantly reduced the risk of adverse events, while proving as effective as the standard of care in preventing death at 10 weeks of treatment.
Cryptococcal meningitis is a severe invasive fungal infection caused by a yeast. It occurs most often in severely immunocompromised patients, primarily late stage HIV patients, and it is the second leading cause of HIV-related death worldwide, claiming approximately 180,000 lives each year, mainly in Sub-Saharan Africa.
The AMBITION trial1, which led to this publication, was conducted by an international consortium using data from five countries in Sub-Saharan Africa: South Africa, Botswana, Malawi, Uganda and Zimbabwe. At the Institut Pasteur, it involved the Molecular Mycology Unit and its principal investigator Olivier Lortholary. It is the largest randomized clinical trial to have been conducted, including 844 advanced-stage HIV patients presenting with cryptococcal meningitis. The Molecular Mycology Unit is continuing to investigate this fungal infection, especially the mechanisms that enable the fungus to survive inside phagocytic cells like macrophages. The unit is also involved in the design and development of an innovative antigen diagnostic approach based on a quantitative PCR method that will facilitate diagnosis and monitoring of patients receiving treatment for cryptococcal meningitis.
1. The AMBITION trial: AMBIsome Therapy Induction OptimisatioN.
This study is part of the priority scientific area Emerging infectious diseases of the Institut Pasteur's strategic plan for 2019-2023.
Single-Dose Liposomal Amphotericin B Treatment for Cryptococcal Meningitis, New England Journal of Medicine, March 24, 2022
J.N. Jarvis, D.S. Lawrence, D.B. Meya, E. Kagimu, J. Kasibante, E. Mpoza, M.K. Rutakingirwa, K. Ssebambulidde, L. Tugume, J. Rhein, D.R. Boulware, H.C. Mwandumba, M. Moyo, H. Mzinganjira, C. Kanyama, M.C. Hosseinipour, C. Chawinga, G. Meintjes, C. Schutz, K. Comins, A. Singh, C. Muzoora, S. Jjunju, E. Nuwagira, M. Mosepele, T. Leeme, K. Siamisang, C.E. Ndhlovu, A. Hlupeni, C. Mutata, E. van Widenfelt, T. Chen, D. Wang, W. Hope, T. Boyer‑Chammard, A. Loyse, S.F. Molloy, N. Youssouf, O. Lortholary, D.G. Lalloo, S. Jaffar, and T.S. Harrison, for the Ambition Study Group