Race against time: New treatment for deadly HIV complication enters trials
The trial is testing a new easy-to-administer and patient-friendly sustained-release formulation of flucytosine, a key medication in the treatment of the HIV-linked meningitis.
What you need to know:
- Cryptococcal meningitis is a serious fungal infection that commonly affects individuals with advanced HIV disease.
- It is a major cause of HIV-related deaths.
A crucial drug for treating a deadly opportunistic infection common in individuals with advanced HIV disease has entered Phase II clinical trials in Africa, offering fresh hope to people living with the virus and overburdened health systems.
The trial is testing a new easy-to-administer and patient-friendly sustained-release formulation of flucytosine, a key medication in the treatment of the HIV-linked meningitis.
Cryptococcal meningitis is a serious fungal infection that commonly affects individuals with advanced HIV disease. It is a major cause of HIV-related deaths.
The development has come at a critical time, with the Drugs for Neglected Diseases initiative (DNDi) warning that cases of cryptococcal meningitis are likely to rise due to shrinking access to HIV care.
This follows the withdrawal of the US President's Emergency Plan for AIDS Relief (PEPFAR), placing the sustainability of HIV treatment at risk in several donor-dependent countries.
“The new flucytosine formulation simplifies dosing from four times to twice daily. It comes in pellet form, making it easier to take with water or through a nasogastric tube. It is suitable for outpatient self-administration,” says Dr Luis Pizarro, executive director of DNDi.
Flucytosine, an effective and key component of the World Health Organization’ss first-line treatment regimen for cryptococcal meningitis, is difficult to administer in overburdened, resource-limited settings.
Defaulting medication
The medication is taken four times per day, with a number of eligible patients at risk of defaulting medication.
Some of the patients on medication at times arrive in hospital already in a coma, forcing healthcare staff to crush the tablets and administer them via nasogastric tube, a method not formally approved but often the only available option.
“We were already struggling with limited supplies of flucytosine across many countries. With the HIV funding cuts, the situation is becoming worse. Widespread stock-outs are just around the corner. Without this life-saving drug, preventable deaths are inevitable,” says Dr Justine Odionyi, head of HIV Disease at DNDi.
Cryptococcal meningitis is caused by the fungus Cryptococcus neoformans, found in soil and bird droppings, and is a major health threat to people with weakened immune systems.
The disease is associated with severe illness, morbidity and mortality, especially in sub Saharan Africa , as per the WHO reports.
The opportunistic disease often begins with severe headaches, fever, nausea, and vomiting. It progresses to patients experiencing neck stiffness, confusion and in late stages, coma due to inflammation of the brain and spinal cord.
According to the Centre for Disease Control, the health condition is common in countries with high HIV prevalence and limited access to healthcare; with an estimated 152,000 cases recorded annually.
Out of the reported cases, 112,000 result in deaths every year; with a majority occurring in sub-Saharan Africa.
In Kenya, latest statistics from the National AIDS and STI Control Programme reveal that 1.4 million Kenyan adults and 71,433 children were living with HIV by 2023.
Earlier this year, Kenya was ranked by WHO among countries at risk of running out of HIV drugs following the recent decision by the US government to pause foreign aid.
Dr Pizarro stressed that when people living with HIV are barred from accessing treatment, they risk developing advanced HIV disease and become vulnerable to deadly infections like cryptococcal meningitis.
The expert pointed out lack of access to timely diagnosis and treatment as a major reason cryptococcal meningitis remains deadly.
The other challenges to the disease management include short supply of point-of-care CD4 testing, growing shortages of cryptococcal antigen lateral flow assay tests, fewer diagnostic tools and the shrinking healthcare workforce.
“As HIV funding cuts threaten to undo decades of progress in Africa, treatment interruptions are already threatening to push thousands into advanced HIV disease (AHD). Essential AHD services have been disrupted, and stock-outs of life-saving medicines like flucytosine are looming,” says the medical expert.
Also read: Managing meningitis in people living with HIV
He adds: “In the wake of this unprecedented crisis, we must continue developing new treatment options for people living with HIV/Aids and urgently strengthen international scientific collaborations.”
The Phase II clinical trial is being conducted by DNDi in partnership with Mylan Laboratories Limited, India (a Viatris Company), the National Institute for Medical Research, among other partners in Malawi and Tanzania with 72 adult participants.
The participants will be divided into two groups: one receiving the current regimen of flucytosine every six hours for 14 days, while the other will receive the new sustained-release version 6000 mg taken twice daily.
If successful, the new formulation could save lives by improving adherence and easing strain on health systems.
