Immediate-release flucytosine & liposomal amphotericin B access
Address the supply and demand barriers limiting access to immediate-release flucytosine and liposomal amphotericin B in low- and middle-income countries
current phase of drug development
updated 18 Mar 2024
Cryptococcal meningitis is one of the leading causes of death in people with advanced HIV. About 180,000 people a year, mostly in Africa, die from HIV-related cryptococcal meningitis. While undiagnosed and untreated fungal meningitis is fatal, over 70 percent of people can survive if they receive early and optimal treatment. However, despite advancements in access to antiretroviral therapy, many low- and middle-income countries (LMICs) have no access to diagnostics, such as the cryptococcal antigen lateral flow assay (CrAg LFAs), and essential medicines, including immediate-release (IR) flucytosine (5FC) and amphotericin B (AmB) recommended by WHO for the treatment of cryptococcal meningitis.
Results from the AMBITION-cm study released at the 11th IAS conference in 2021 demonstrated that single, high-dose liposomal amphotericin B (LAmB), given with flucytosine and fluconazole, is as good in avoiding death after 10 weeks as the current WHO-recommended standard of care. Moreover, this combination was associated with a significant reduction in adverse events. As with 5FC, access to LAmB, which is also recommended for use across several other diseases including visceral leishmaniasis, is extremely limited in LMICs.
In collaboration with key in-country and international partners, DNDi is addressing access barriers and working to unblock market failures limiting access to the two medicines in LMICs. Key priorities include identifying alternative quality-assured manufacturers of injectable LAmB, implementing activities to bring at least one product to the LMIC market, and tracking progress toward improved access to reach public health targets. In addition, we are undertaking demand creation activities for both LAmB across key indications and IR 5FC for cryptococcal meningitis, alongside implementing mechanisms to track progress towards public health targets for advanced HIV disease.
Project updates
2023
DNDi and the HIV Policy Lab completed development of the Advanced HIV Disease (AHD) Dashboard, an online resource that maps national guidelines for AHD and cryptococcal meningitis across 35 African countries. The dashboard serves to monitor progress and encourage countries to fast-track full adoption of life-saving interventions against AHD. It also aims to reduce the time lag between the generation of scientific evidence and adoption of revised policies by national health authorities. The AHD dashboard and an accompanying policy brief were launched at the 22nd International Conference on AIDS and STIs in Africa (ICASA) in December 2023.
2022
With the Clinton Health Access Initiative (CHAI) and St George’s, University of London, DNDi co-convened a multi-country meeting on access to therapeutics and diagnostics for advanced HIV disease (AHD) in December 2022. Attended by representatives from ministries of health, expert clinicians, supply chain specialists, civil society, patient representatives, and donors, the 3-day meeting in Nairobi, Kenya, sought to share best practices and address barriers to treatment in 13 countries with a high disease burden.
A request for proposals to produce generic liposomal amphotericin B (LAmB) was launched in collaboration with CHAI and Unitaid, with the aim of securing at least one affordable, quality-assured generic product in 2023/2024. Access activities related to immediate-release flucytosine continued throughout the year, with several countries adopting the updated WHO treatment guidelines released in April 2022.
2021
Together with St George’s, University of London; WHO; and CDC Foundation, DNDi co-hosted two satellite sessions on advanced HIV disease and cryptococcal meningitis at the 11th IAS Conference on HIV Science held in July 2021. The sessions, a call to action to address access barriers for the management of cryptococcal meningitis, brought together multiple stakeholders, including global policy making institutions, donors, ministries of health, country implementing partners, civil society, and patient advocates.
DNDi also collaborated with the Clinton Health Access Initiative on a LAmB landscape and gap analysis, including a technical assessment of potential alternative suppliers, market analyses of the cost of goods, and commercial discussions. Follow-up activities were identified for action.
News & resources
- 15 August 2024 - Paving the way for affordable and equitable liposomal amphotericin B access worldwide, The Lancet Global Health
- 28 March 2024 - 2023 R&D portfolio in review: HIV
- 8 March 2022 - Cryptococcal meningitis: An improved formulation of a lifesaving treatment
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