What it is
This new therapy, a single high-dose of liposomal Amphotericin B, is as effective as the traditional week-long regimen, easier to administer, and causes fewer side effects. It is now the WHO-recommended therapy for cryptococcal meningitis.
Why it matters
Despite highly effective HIV treatments, opportunistic infections such as cryptococcal meningitis continue to cause significant morbidity and mortality, accounting for around 200,000 AIDS-related deaths annually. This new therapy can help save lives and improve the health of people living with HIV.
The story
Decades of progress in antiretroviral therapy (ART) have transformed the fight against HIV, saving millions of lives and dramatically improving the quality of life.[1] Yet HIV remains incurable and intertwined with other severe conditions like tuberculosis, cryptococcosis, and cancer, as well as deep socioeconomic and mental health challenges.[2] Ending the HIV epidemic requires a deeper understanding of HIV-associated diseases and the development of effective solutions.
Cryptococcosis is a highly infectious airborne fungal disease that can affect the brain, lungs, and other organs. It is one of the most common infections in people living with HIV and a major contributor to severe illness, morbidity, and mortality.[3] Even among ART-treated patients, cryptococcal mortality remains high; approximately 70% in low- and middle-income countries and 20–30% in high-income countries.[4] Meningitis caused by cryptococcal disease accounts for roughly 15% of all AIDS-related deaths: close to 200,000 people each year.
Despite this, cryptococcal meningitis remains severely under-studied[5] with current therapies relying on medicines developed over half a century ago. The current treatment involves a complex three-drug regimen: one week of intravenous amphotericin B combined with oral flucytosine and fluconazole, alongside continued ART. This demanding treatment requires specialist monitoring and carries significant toxicity risks. Even with generic formulations, drug availability in Africa is limited, and daily intravenous administration is logistically challenging.[6]
To address this, EDCTP funded the AMBITION-cm trial, the largest clinical study of cryptococcal meningitis in HIV patients to date.[7] Building on previous trials, this study confirmed that a single high-dose intravenous regimen of amphotericin B is as effective as standard therapy, easier to administer, and associated with fewer side effects.[8] This regimen is now the WHO-recommended treatment for cryptococcal meningitis. Its efficacy[9] and cost-effectiveness[10] have also been reconfirmed in follow-up studies.
Despite these advances, gaps remain in understanding and addressing HIV-related diseases, including cryptococcal meningitis. Global Health EDCTP3 continues to support the development of new and improved technologies targeting HIV[11] and HIV-associated diseases, including tuberculosis,[12] and focusing on priority populations such as children and pregnant women.[13]
Sources:
[2] Chronic comorbidities & coinfections among PLHIV. Global HIV Programme
[3] Guidelines for diagnosing, preventing and managing cryptococcal disease among adults, adolescents and children living with HIV
[4] Therapy for HIV-associated cryptococcal meningitis: a case report demonstrating a new treatment approach emphasizing updated treatment guidelines - PMC
[5] Filling the gap in funding for research on cryptococcal meningitis with HIV - eMagazine November 2021
[6] Treatment of Cryptococcal Meningitis: How Have We Got Here and Where are We Going? | Drugs
[7] AMBITION-cm - International partnerships against infectious diseases
[8] Single dose of liposomal amphotericin B as effective in treating HIV-associated cryptococcal meningitis as current standard of care - EDCTP
[9] Implementation of Single High-dose Liposomal Amphotericin B Based Induction Therapy for Treatment of HIV-associated Cryptococcal Meningitis in Uganda: A Comparative Prospective Cohort Study | Clinical Infectious Diseases | Oxford Academic
[10] Cost-effectiveness of single, high-dose, liposomal amphotericin regimen for HIV-associated cryptococcal meningitis in five countries in sub-Saharan Africa: an economic analysis of the AMBITION-cm trial
[11] Developing novel, innovative HIV therapeutics for reducing the disease burden of HIV in sub-Saharan Africa | Programme | HORIZON | CORDIS | European Commission
[12] Intensified tuberculosis treatment to reduce the high mortality of tuberculous meningitis in HIV-infected and uninfected patients | INTENSE-TBM-2 | Project | Fact Sheet | HORIZON | CORDIS | European Commission & Evaluating a new stool based qPCR for diagnosis of tuberculosis in children and people living with HIV | STOOL4TB | Project | Fact Sheet | HORIZON | CORDIS | European Commission
[13] Drug Optimisation in LMICs of Pregnant HIV women and their Infants: temporary switch to CAB/RPV long acting injections | DOLPHIN-3 | Project | Fact Sheet | HORIZON | CORDIS | European Commission
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This new therapy, a single high-dose of liposomal Amphotericin B, is as effective as the traditional week-long regimen, easier to administer, and causes fewer side effects. It is now the WHO-recommended therapy for cryptococcal meningitis.
Our added value for Europe
EDCTP boosts Europe’s competitiveness by advancing research excellence, innovation, and public–private cooperation in global health. By supporting late-stage development and Africa–Europe partnerships, it bridges the EU innovation gap and creates new market and investment opportunities.
EDCTP strengthens Europe’s health security by tackling climate-sensitive diseases and antimicrobial resistance, enhancing surveillance, and accelerating medical countermeasures. Its rapid crisis responses, from Ebola to COVID-19, show its agility in protecting Europe and global health.
EDCTP drives Europe’s science diplomacy through fair Africa–Europe partnerships that tackle global health challenges. Its equitable governance and ethical research practices strengthen EU credibility and global influence.
EDCTP strengthens Europe’s leadership in digital health by investing in AI, data, and digital technologies while training researchers in fields like bioinformatics and genomic epidemiology.
EDCTP advances the EU’s human rights goals by promoting ethical, inclusive research that addresses unmet medical needs. It ensures innovations reach vulnerable populations while strengthening local scientific and health systems.
Our added value for Africa
EDCTP improves health and prosperity in Africa by funding clinical research, strengthening local capacities, and empowering African scientists. Its investments reduce the burden of infectious diseases, boost productivity, and support sustainable development across the continent.
EDCTP builds Africa’s capacity to detect, prevent, and respond to outbreaks through training, research, and strong partnerships. Its work accelerates vaccine and diagnostic development and reinforces the continent’s health resilience.
EDCTP strengthens Africa’s clinical research ecosystem by investing in skills, infrastructure, and regulatory systems. Initiatives like CTCAN and PACTR connect researchers and regulators, expanding quality trials and fostering local leadership.
EDCTP strengthens Africa-led health partnerships with organisations like Africa CDC and WHO AFRO, aligning research and investment with continental priorities. As an AU–EU Innovation Agenda partner, it builds skills, fosters co-investment, and drives sustainable cooperation.
EDCTP promotes health equity by developing practical solutions for underserved communities, including newborns and children, women, urban poor and rural communities. It funds accessible technologies and digital tools that expand healthcare reach and improve outcomes for those most in need.