NIHR Global Health Research Group on HIV-associated Fungal Infections (IMPACT-AIDS MYCOSES) Invasive fungal infections are a growing global threat to human health, affecting >150 million people and accounting for up to 1.5 million deaths per year. However, this burden is under-appreciated and medical mycology is chronically underfunded. Research into improvements in diagnosis and treatment and implementation of this research are essential to reduce death and disability. HIV remains a leading cause of morbidity and mortality in low- and middle-income countries (LMICs) causing an estimated 500,000 to 1 million deaths annually, the majority in sub-Saharan Africa and South East Asia. Four HIV-associated fungal infections - cryptococcal meningitis, talaromycosis, Pneumocystis pneumonia (PCP), and histoplasmosis - are responsible for 250,000 deaths per year, and up to 20% of all HIV-associated mortality. The World Health Organization (WHO) has recognized that HIV deaths cannot be further reduced until these major fungal complications of advanced HIV disease are effectively addressed. Our NIHR Global Health Group aims to capitalise on the opportunities presented by recent clinical research advances in cryptococcal meningitis to improve the diagnosis and treatment not just of cryptococcal meningitis, but also the three other major HIV-associated mycoses of public health importance. Our group brings together leading academic researchers, clinical and public health leaders, non-governmental organisations (NGOs) including Médecins Sans Frontières and the Drugs for Neglected Diseases initiative, and community and patient representatives, to improve the diagnosis and treatment of these HIV-associated fungal infections and ensure that these improvements are made widely available to populations most commonly affected in Africa (Democratic Republic of Congo, Mozambique, Guinea, Malawi, Botswana, South Africa), and South East Asia (Vietnam). Our partnership will be equitable, with leadership shared across six work packages delivered over 4 years from 2022 through to 2026, insights from qualitative research, guidance from a steering committee and community advisory boards, and priorities set at initial meetings led by LMIC partners. In addition to the direct impact of the work, we will liaise with national, regional, and international bodies (ministries of health, major NGOs, UNITAID, WHO) in order to effectively scale the results and impact of our work. 1. TREATMENT: To implement novel, short-course treatment for HIV-associated cryptococcal meningitis in routine care in African and South East Asian countries, building on the results of two landmark trials, ACTA and AMBITION-cm, completed by partners in our consortium, both of which demonstrated improved survival with regimens that are practical and affordable in resource-limited settings. And to support preliminary work using a single high-dose liposomal amphotericin B treatment approach in talaromycosis and to lay the foundations for future studies in histoplasmosis.
2. PREVENTION: To optimize the screen-and-treat strategy, to identify and treat early cryptococcal disease, before it becomes clinically apparent, in Africa and South East Asia. Semi-quantitative tests will be evaluated for cryptococcal antigen screening, and the pharmacokinetics of pre-emptive treatment with sustained-release flucytosine will be determined, within the ongoing EFFECT trial. Screening will be evaluated to prevent talaromycosis, cryptococcosis and histoplasmosis in South East Asia and histoplasmosis and emergomycosis in Africa. 
3. HEALTH ECONOMICS: To generate essential economic data to support the different screening and treatment approaches being investigated for cryptococcosis, histoplasmosis and talaromycosis. These individual and, if appropriate, combined analyses will be crucial evidence in our efforts to effect the policy changes needed to reduce mortality from HIV-associated fungal infections. 
4. DIAGNOSTICS: To initiate a programme of earlier-stage, laboratory-based work on HIV-associated Pneumocystis pneumonia (PCP), and to develop a clinical cohort and sample bio-bank as a resource to develop and test novel diagnostic tests for PCP, which constitutes the major barrier to reducing PCP deaths.
5. TRAINING: As integral to the work proposed, to support a comprehensive training and capacity strengthening programme in clinical (epidemiology, health economics and/or public health), and laboratory research, and including 3 laboratory MSc, 2 taught MSc and 3 PhD places. Training will be enabled by a recent strategic UK-African partnership based at the University of Cape Town (UCT), South Africa between the UK MRC Centre for Medical Mycology and UCT, and will build on our extensive experience of training and capacity strengthening within existing multinational projects. Our goal is to train and mentor clinicians and researchers who will help drive and develop this partnership beyond the initial 4-year period.
6. ENGAGEMENT: To ensure that the voices of people living with advanced HIV disease and community representatives are meaningfully included and heard across the entire scope of work, we will develop strategies and tools to increase patient health literacy around HIV-associated fungal infections, collect qualitative data to learn from the experience of patients with HIV-associated fungal infections and facilitate meaningful engagement through our community advisory boards. We acknowledge and affirm that successful implementation of our work is dependent on the engagement of patients and communities.