Drugs for Neglected Diseases initiative (DNDi) and its partners has announced a promising new development that will bring much-needed relief to thousands of patients battling advanced HIV disease in sub-Saharan Africa as a new, patient-friendly sustained-release formulation of flucytosine—an essential drug used to treat deadly cryptococcal meningitis—has entered Phase II clinical trials in Malawi and Tanzania.
Led by the not-for-profit Drugs for Neglected Diseases initiative (DNDi) and its partners, the trial offers a beacon of hope for those confronting the deadly consequences of advanced HIV and its opportunistic infections at a time of donor funding uncertainties.
“Treatment interruptions are already threatening to push thousands into advanced HIV disease (AHD),” warned Dr. Luis Pizarro, Executive Director of DNDi. “Essential AHD services have been disrupted, and stock outs of life-saving medicines like flucytosine are looming.”
The health crisis comes as international funding for HIV programs shrinks, threatening to unravel decades of progress. In 2023 alone, 390,000 people in Africa died from AIDS-related illnesses. A staggering 130,000 of those deaths were due to cryptococcal meningitis—a brutal, opportunistic fungal infection that targets people with weakened immune systems, particularly those with advanced HIV.
Cryptococcal meningitis, caused by Cryptococcus neoformans, progresses quickly and fatally. Its symptoms begin with intense headaches, fever, and nausea, and escalate to confusion, coma, and death if untreated. The disease’s lethality—up to 70percent in many parts of Africa—is largely due to delayed diagnosis and difficult-to-administer treatments.
Flucytosine has long been a cornerstone in treating cryptococcal meningitis, but its current form poses a host of challenges. Patients must take it every six hours for two weeks—an impractical schedule in overstretched healthcare systems. Many arrive at hospitals already unconscious, requiring the tablets to be crushed and delivered through nasogastric tubes, a method not officially approved.
The new sustained-release formulation changes that equation. Administered just twice a day in pellet form, it is easier for patients to take with water or via feeding tube, and suitable for outpatient care.
“The current flucytosine formulation is difficult to administer, which has impacted treatment outcomes for years,” said Dr. Cecilia Kanyama, Principal Investigator at the University of North Carolina Project in Malawi. “We’re hopeful this new formulation will be easier to use and lead to better outcomes for our patients.”
The open-label, randomized Phase II study will enroll 72 adult participants—36 in Malawi and 36 in Tanzania. One group will receive the standard regimen of flucytosine (every six hours for 14 days), while the other will receive 6000 mg of the new sustained-release version twice daily. The simplified regimen could ease pressure on healthcare workers, reduce missed doses, and improve patient outcomes.
For healthcare professionals on the frontlines, the trial is more than good news to them.
“We were already struggling with limited supplies of flucytosine,” said Dr. Justine Odionyi, Head of HIV Disease at DNDi. “Now, with the HIV funding cuts, the situation is becoming worse. Widespread stockouts are just around the corner. Without this life-saving drug, preventable deaths are inevitable.”
Diagnostic tools are also becoming scarce. CD4 count tests and cryptococcal antigen lateral flow assays—vital for identifying those at risk—are in short supply, and healthcare systems across the region are stretched thin.
“In Tanzania, around 1.4 million people depend on antiretroviral therapy to manage HIV,” noted Prof. Sayoki Mfinanga of the National Institute for Medical Research. “We’ve been telling people HIV is no longer a death sentence—if you can access and stay on treatment. But with supply chains under threat, that progress is at risk.”
As multilateral support for HIV care falters, initiatives like this new flucytosine trial highlight the critical role of scientific innovation and international collaboration. They represent a lifeline for patients who are too often forgotten in global health priorities.
“In the face of this unprecedented crisis,” said Dr. Pizarro, “we must continue developing new treatment options for people living with HIV/AIDS and urgently strengthen international scientific collaborations.”
