In 2018, WHO issued guidelines for the diagnosis, prevention, and management of HIV-related cryptococcal disease. Two strategies are recommended to reduce the high mortality associated with HIV-related cryptococcal meningitis in low-income and middle-income countries (LMICs): optimised combination therapies for confirmed meningitis cases and cryptococcal antigen screening programmes for ambulatory people living with HIV who access care. WHO's preferred therapy for the treatment of HIV-related cryptococcal meningitis in LMICs is 1 week of amphotericin B plus flucytosine, and the alternative therapy is 2 weeks of fluconazole plus flucytosine. In the ACTA trial, 1-week (short course) amphotericin B plus flucytosine resulted in a 10-week mortality of 24% (95% CI −16 to 32) and 2 weeks of fluconazole and flucytosine resulted in a 10-week mortality of 35% (95% CI −29 to 41). However, with widely used fluconazole monotherapy, mortality because of HIV-related cryptococcal meningitis is approximately 70% in many African LMIC settings. Therefore, the potential to transform the management of HIV-related cryptococcal meningitis in resource-limited settings is substantial. Sustainable access to essential medicines, including flucytosine and amphotericin B, in LMICs is paramount and the focus of this Personal View.
Bibliographical noteFunding Information:
NG received personal fees from Astellas Pharma and non-financial support from MSD outside the submitted work. JD received personal fees from Viamet Pharmaceuticals outside the submitted work. JNJ received grants from Gilead Sciences Europe outside the submitted work. TB received grants and personal fees from Gilead Sciences Inc outside the submitted work. RH received grants from Medical Research Council and Wellcome Trust during the conduct of the study. TSH received grants from Medical Research Council (UK), ANRS (France), Gilead Sciences, and Immunomycologics and personal fees from Viamet, Gilead Sciences, and Pfizer during the conduct of the work. OL received personal fees from MSD, Astellas Pharma, Pfizer, and Gilead outside the submitted work. DD and family hold founder shares in F2G Ltd, a University of Manchester spin-out antifungal discovery company. DD acts or has recently been a consultant to Scynexis, Cidara, Quintiles, Pulmatrix, Pulmocide, Zambon, Roivant, and Fujifilm. In the past 3 years, he has been paid for talks on behalf of Astellas, Dynamiker, Gilead, Merck, Mylan, and Pfizer. He is a member of the Infectious Disease Society of America Aspergillosis Guidelines group, the European Society for Clinical Microbiology, Infectious Diseases Aspergillosis Guidelines group, and the British Society for Medical Mycology Standards of Care committee. DD has a patent licenced for Assays for Fungal Infection. All other authors declare no competing interests.
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