New effective short-term treatment for HIV-associated cryptococcal meningitis

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

According to estimates produced by the London School of Hygiene and Tropical Medicine, cryptococcal meningitis, a fungal infection that invades the lining of the brain, kills more than 180,000 people each year worldwide, with 75% 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 in reducing deaths as the WHO-recommended seven-day treatment with amphotericin-B.

“Single-dose liposomal amphotericin B plus flucytosine and fluconazole was not inferior to WHO-recommended treatment for HIV-associated cryptococcal meningitis and was associated with fewer adverse events,” the study states. , 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 in five southern and eastern African countries with no loss to follow-up, our results are likely to be generalizable to other African settings with high HIV prevalence.”

Joseph Jarvis, lead author and research associate at the Botswana Harvard AIDS Partnership Institute, says cryptococcal meningitis is a serious disease in people living with HIV and is the most common cause of meningitis in adults, especially in East Africa. and southern. It is responsible for approximately 15% of all HIV-related deaths worldwide.

“Until now, the most commonly used treatments in Africa have been a drug called fluconazole which is associated with 60-70% mortality rates, or two weeks of intravenous therapy with a drug called amphotericin B which is associated with serious side effects, and requires intensive nursing care and laboratory monitoring to be administered safely,” says Jarvis SciDev.Net.

Jarvis explains that at the individual patient level, people only need one dose of medication instead of seven doses, which sometimes requires the placement of painful intravenous needles. He adds that patients are much less likely to suffer life-threatening side effects, including anemia, kidney dysfunction and infections from intravenous drips.

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

Marybeth Cherono Maritim, a senior lecturer in the Department of Clinical Medicine and Therapeutics at the University of Nairobi, says the study has positive implications for the treatment of HIV-associated meningitis as the diet is safe and effective.

“The only challenge with implementing these findings is that flucytosine and liposomal amphotericin B are not readily available in the public sector in Kenya and many other sub-Saharan countries that bear the brunt of cryptococcal meningitis,” she said. SciDev.Net.

Maritim adds that in some African countries like Guinea, Mozambique, Niger, Sudan and Tunisia, flucytosine is not registered with regulatory authorities. Also, flucytosine and liposomal amphotericin B are expensive. Amphotericin B must be transported and stored at low temperatures.

Maritim says a high-level advocacy and access program that has worked in expanded immunization programs and more recently in access to COVID-19 vaccines should be adopted to facilitate access in countries across Africa sub-Saharan Africa with limited resources.

Jarvis says, “If the study results are widely implemented across Africa, the new single-dose treatment has the potential to facilitate the treatment of this serious infection in patients with advanced HIV disease and contribute to global efforts to reduce or eliminate deaths from cryptococcosis. meningitis by 2030.”

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

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