Doctors Without Borders (MSF) welcomes the updated World Health Organization (WHO) guidelines for the management of cryptococcal meningitis, an opportunistic fungal infection, which is the number two killer of people living with HIV/AIDS after tuberculosis. The guidelines endorse a simplified regimen, following the important results of the AMBITION trial, consisting of a single high dose of liposomal amphotericin B (L-AmB), combined with two weeks of flucytosine and fluconazole, as the preferred treatment option.
With new WHO global targets set to reduce deaths from cryptococcal meningitis by 50% in 2025 and 90% by 2030, MSF urges all countries to urgently adopt these guidelines to save the lives of people living with HIV/AIDS.
However, access to L-AmB and flucytosine remains a significant challenge in low- and middle-income countries due to a combination of factors including the drugs not being included in national guidelines and countries not submitting requests to donors such as the Global Fund and PEPFAR to fund the procurement of these lifesaving medicines.
To begin addressing the challenges of accessing L-AmB and flucytosine, governments need to update national cryptococcal meningitis clinical guidance urgently, include these medicines in funding requests from major donors, and increase screening for cryptococcal meningitis among people living with HIV. Governments need to work with pharmaceutical companies and urge them to increase production and expand registration of these medicines to meet the expected increase in demand as countries start to adapt and implement the new guidelines.
Additionally, US corporation Gilead, the main supplier of quality-assured L-AmB, has failed to deliver on its promise of providing this lifesaving medicine at the access price of $16.25 per vial to treat cryptococcal meningitis (which would allow for the inclusion of L-AmB at approximately $195 per person under the new recommended treatment protocol) as promised to 116 countries in 2018. More than three years later, Gilead has still only provided L-AmB to less than half of the eligible countries at the access price.
Furthermore, Gilead has done little to expand access in terms of the registration of L-AmB where it is needed most – with registrations in only two countries in all sub-Saharan Africa. In addition, despite multiple quality-assured generic manufacturers of flucytosine in the market, few have been registered and made available in low- and middle-income countries.
Dr Freddy Mangana, HIV-TB Medical Supervisor for MSF in the Democratic Republic of Congo:
“With timely and effective diagnosis and treatment, people living with HIV/AIDS can survive opportunistic infections like cryptococcal meningitis. We are optimistic that the new treatment regimen recommended in the WHO guidelines will be adopted quickly by countries, as it is much simpler to give, can be started immediately in some settings, is better tolerated and will hopefully lead to shorter hospital stays for many patients. However, the limited availability of quality-assured L-AmB and flucytosine means that treatment providers working in sub-Saharan Africa struggle to treat people with cryptococcal meningitis or risk treating them with suboptimal treatments when these medicines are not available. The good news is that this new regimen also uses less L-AmB and requires less monitoring, which could reduce the overall price for countries to implement as compared to the previous L-AmB regimen if urgently adopted into national guidelines.”
We are encouraged that the WHO guidelines now include a simplified treatment regimen for people with cryptococcal meningitis, but it’s disheartening to see the persistent challenges to accessing the required medicines. This lifesaving treatment remains out of reach and unaffordable for far too many people who need it.Dr Freddy Mangana, HIV-TB Medical Supervisor for MSF in the Democratic Republic of Congo
To ensure we meet the new WHO targets for decreasing deaths from cryptococcal meningitis, Gilead needs to do everything it can to make good on its promise to provide L-AmB at their access price. In addition, there needs to be a significant effort from countries to prioritise the use of L-AmB and flucytosine, and from manufacturers to start registering and supplying these medicines.