New short-course treatment effective against HIV-associated cryptococcal meningitis

A new short-course treatment is effective against HIV-associated cryptococcal meningitis with fewer serious side effects, and has the potential to reduce the length and cost of hospital admissions, a study shows.

According to estimates produced by the London School of Hygiene and Tropical Medicine, cryptococcal meningitis, a fungal infection which invades the lining of the brain, kills over 180,00 every year globally, with 75 per cent of deaths occurring in Sub-Saharan Africa.

The trial, conducted in Botswana, Malawi, South Africa, Uganda, and Zimbabwe, assessed whether combining two oral antifungals — fluconazole and flucytosine — with a single high dose of liposomal amphotericin-B could be as effective at reducing deaths as the WHO-recommended seven-day treatment with amphotericin-B.

"Single-dose liposomal amphotericin B combined with flucytosine and fluconazole was noninferior to the WHO-recommended treatment for HIV-associated cryptococcal meningitis and was associated with fewer adverse events," says the study, published last month in the New England Journal of Medicine.

The study adds: "Because this clinical trial involving HIV-positive adults with cryptococcal meningitis was conducted in a range of healthcare settings across five countries in Southern and Eastern Africa with no loss to follow-up, our results are likely to be generalizable to other African settings with a high prevalence of HIV."

Joseph Jarvis, lead author and a research associate at the Botswana Harvard AIDS Partnership Institute, says that cryptococcal meningitis is a severe disease in people with HIV, and is the most common cause of meningitis in adults, especially in East and Southern Africa. It causes about 15 per cent of all deaths related to HIV globally.

"Until now, the most frequently used treatments in Africa have been a drug called fluconazole which is associated with death rates of 60 to 70 per cent, or two weeks of intravenous therapy with a drug called amphotericin B which is associated with severe side effects, and requires intensive nursing care and laboratory monitoring to administer safely," Jarvis tells SciDev.Net.

Jarvis explains that at individual patient level, people only need to have one dose of the medication rather than seven doses, which sometimes require painful intravenous needles to be in place. He adds that patients are much less likely to suffer from potentially life-threatening side effects including anemia, kidney dysfunction, and infections related to the intravenous infusions.

"We performed some detailed interviews with both patients and their healthcare providers as part of the study, and both the patients and staff expressed a strong preference for the single-dose liposomal amphotericin regimen over conventional therapy," he says.

Marybeth Cherono Maritim, a senior lecturer at the University of Nairobi's Department of Clinical Medicine and Therapeutics, says the study has positive implications for treating HIV-associated meningitis because the regimen is safe and efficacious.

"The only challenge with the implementation of these findings is that both flucytosine and liposomal amphotericin B are not readily available in the public sector in Kenya and many other Sub-Saharan countries which bear the brunt of cryptococcal meningitis," she tells SciDev.Net.

Maritim adds that in some African countries such as Guinea, Mozambique, Niger, Sudan, and Tunisia, flucytosine is not registered with the regulatory authorities. Also, both flucytosine and liposomal amphotericin B are costly. Amphotericin B needs to be transported and stored at low temperatures.

Maritim says that a high-level advocacy and access programme that have worked in expanded programmes of immunizations and more recently in providing access to COVID-19 vaccines should be embraced to facilitate access in resource-constrained countries of Sub-Saharan Africa.

Jarvis says: "If the findings of the study are widely implemented across Africa, the new single-dose treatment is likely to make treatment of this severe infection in patients with advanced HIV disease easy and contribute to global efforts to reduce or eliminate deaths from cryptococcal meningitis by 2030."

He adds that policymakers should embrace the findings, which are already changing clinical practice and national treatment guidelines in countries where the trial was conducted. For example, patients in Malawi are already receiving the new treatment through their national HIV programme.