Adjunctive Dexamethasone in HIV-Associated Cryptococcal Meningitis

• Published in: The New England journal of medicine Vol. 374; no. 6; pp. 542 - 554
• Main Authors: Beardsley, Justin, Wolbers, Marcel, Kibengo, Freddie M, Ggayi, Abu-Baker M, Kamali, Anatoli, Cuc, Ngo Thi Kim, Binh, Tran Quang, Chau, Nguyen Van Vinh, Farrar, Jeremy, Merson, Laura, Phuong, Lan, Thwaites, Guy, Van Kinh, Nguyen, Thuy, Pham Thanh, Chierakul, Wirongrong, Siriboon, Suwatthiya, Thiansukhon, Ekkachai, Onsanit, Satrirat, Supphamongkholchaikul, Watthanapong, Chan, Adrienne K, Heyderman, Robert, Mwinjiwa, Edson, van Oosterhout, Joep J, Imran, Darma, Basri, Hasan, Mayxay, Mayfong, Dance, David, Phimmasone, Prasith, Rattanavong, Sayaphet, Lalloo, David G, Day, Jeremy N
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 11.02.2016
• Subjects: Adult; AIDS-Related Opportunistic Infections - drug therapy; AIDS-Related Opportunistic Infections - mortality; Amphotericin B; Antigens; Cerebrospinal fluid; Cerebrospinal Fluid - microbiology; Cerebrospinal Fluid Pressure; Clinical trials; Colony Count, Microbial; Cryptococcus neoformans - isolation & purification; Dexamethasone; Dexamethasone - adverse effects; Dexamethasone - therapeutic use; Double-Blind Method; Drug therapy; Female; Fluconazole; Glucocorticoids; Glucocorticoids - adverse effects; Glucocorticoids - therapeutic use; HIV; Human immunodeficiency virus; Humans; Infections; Kaplan-Meier Estimate; Male; Meningitis; Meningitis, Cryptococcal - drug therapy; Meningitis, Cryptococcal - mortality; Mortality; Patients; Steroids; Treatment Failure; Uganda; Vietnam
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa1509024

The role of glucocorticoids in the treatment of bacterial or fungal meningitis is controversial. In this trial, adjunctive dexamethasone therapy in patients with HIV-associated cryptococcal meningitis did not confer a benefit and was associated with increased adverse events. Cryptococcal meningitis associated with human immunodeficiency virus (HIV) infection is estimated to cause more than 600,000 deaths each year, the vast majority in sub-Saharan Africa and in South and Southeast Asia. 1 Among patients receiving combination antifungal therapy with amphotericin B and either flucytosine or fluconazole, mortality remains more than 30% at 10 weeks, and survivors often have substantial disability. 2 , 3 There is a pressing need to improve outcomes. However, no new anticryptococcal agents are currently close to approval for clinical use, so innovative strategies are needed. Adjunctive treatments, such as glucocorticoids, have shown some benefit in central nervous system (CNS) . . .