5FC HIV-Crypto consortium starts trial on improved treatment of cryptococcal meningitis in advanced HIV disease

25 February 2022

A consortium of leading scientists and institutions in Africa and Europe, the 5FC HIV-Crypto consortium, has launched a project that aims to deliver an improved formulation of a lifesaving treatment for cryptococcal meningitis. This fungal disease is an important cause of morbidity and mortality among people with advanced HIV disease and accounts for an estimated 15% of all HIV-related deaths globally, of which three quarters occur in sub-Saharan Africa.

Left untreated,  fungal meningitis is fatal, but with early and optimal treatment over 70 percent of people can survive.  Flucytosine is a key drug which is used within a combination of treatments. The 5FC HIV-Crypto consortium recently launched a Phase 1 study to develop a new formulation of the existing treatment, known as flucytosine (5FC SR). This new sustained release formulation would only need to be administered twice a day compared to the current treatment of  four times a day.

A Phase II study will follow in 2023 and 2024 in sites in Malawi and Tanzania, where cryptococcal meningitis patients will be enrolled in a randomised, controlled clinical trial to assess the 5FC SR formulation. In tandem with the clinical trial, the consortium will mobilise support for a combination of lifesaving treatments to be more widely available, particularly in African countries that are hard-hit by the disease.

The 5FC HIV-Crypto consortium comprises a selected group of partners with an excellent track record of success delivering new tools and treatment strategies with an impact on public health: DNDi; FARMOVS (a clinical research facility in Bloemfontein, South Africa); investigators from St George’s University of London; the National Institute for Medical Research (NIMR), Tanzania; the Lilongwe Medical Relief Fund Trust (LMRFT) in a partnership with the Kamuzu Central Hospital, Malawi; and the Luxembourg Institute of Health (LIH).

“We are excited about collaborating with committed and outstanding research partners across two continents to develop a better adapted treatment for this devastating illness”

Carol Ruffell, project leader of the 5FC Sustained Release (SR) development programme and director of the DNDi South Africa office

“Cryptococcal meningitis is one of the unacceptably under-studied and under-funded HIV related comorbidities, especially in sub-Saharan Africa. To address this critical gap in such vulnerable populations, EDCTP provides funding to improve treatment and access to essential drugs, as well as diagnosis of cryptococcal infections, as an integral part of healthcare systems. We are very encouraged by the start of this very promising 5FC HIV-Crypto consortium”

Michael Makanga, EDCTP Executive Director

Filling the funding gap

Despite its major burden in sub-Saharan Africa, cryptococcal meningitis remains under-studied and under-funded. The 2019 G-FINDER annual report highlighted the fact that the bulk of non-USA funding was routed through EDCTP, and accounted for 85% of global funding on clinical development. EDCTP currently has a €129.45 million portfolio of HIV research in Africa, including €16.06 million to tackle cryptococcal meningitis.

In addition to improving treatment regimens and access to essential drugs, much needs to be done to improve timely diagnosis of cryptococcal infections and implementing the right procedures in healthcare systems. EDCTP-funded projects on cryptococcal meningitis, including the 5FC HIV-Crypto consortium, are addressing these topics – read about these projects in EDCTP’s eMagazine.