Single High Dose of Liposomal Amphotericin B in Human Immunodeficiency Virus/AIDS-Related Disseminated Histoplasmosis: A Randomized Trial.

Autor:	Pasqualotto AC; Department of Clinical Medicine and Post-Graduation Program in Pathology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil.; Infectious Diseases and Internal Medicine Services, Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, Brazil., Lana DD; Department of Clinical Medicine and Post-Graduation Program in Pathology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil., Godoy CSM; Infectious Diseases Service, Hospital de Doenças Tropicais, Goiânia, Brazil.; Department of Research and Education, Pontifícia Universidade Católica de Goiás, Goiânia, Brazil., Leitão TDMJS; Infectious Diseases Service, Hospital São José de Doenças Infecciosas, Fortaleza, Brazil.; Department of Public Health, Federal University of Ceará, Fortaleza, Brazil., Bay MB; Department of Infectious Diseases, Federal University of Rio Grande do Norte, Natal, Brazil.; Infectious Diseases Service, Giselda Trigueiro Hospital and Instituto de Medicina Tropical do Rio Grande do Norte, Natal, Brazil., Damasceno LS; Infectious Diseases Service, Hospital São José de Doenças Infecciosas, Fortaleza, Brazil.; Department of Public Health, Federal University of Ceará, Fortaleza, Brazil., Soares RBA; Infectious Diseases Service, Hospital de Doenças Tropicais, Goiânia, Brazil.; Department of Research and Education, Pontifícia Universidade Católica de Goiás, Goiânia, Brazil., Kist R; Infectious Diseases and Internal Medicine Services, Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, Brazil., Silva LR; Department of Clinical Medicine and Post-Graduation Program in Pathology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil., Wiltgen D; Department of Clinical Medicine and Post-Graduation Program in Pathology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil.; Infectious Diseases and Internal Medicine Services, Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, Brazil., Melo M; Infectious Diseases Service, Hospital Nossa Senhora da Conceição, Porto Alegre, Brazil., Guimarães TF; Infectious Diseases Service, Hospital de Doenças Tropicais, Goiânia, Brazil., Guimarães MR; Department of Nephrology, Universidade de São Paulo, São Paulo, Brazil., Vechi HT; Department of Infectious Diseases, Federal University of Rio Grande do Norte, Natal, Brazil., de Mesquita JRL; Infectious Diseases Service, Hospital São José de Doenças Infecciosas, Fortaleza, Brazil., Monteiro GRG; Department of Infectious Diseases, Federal University of Rio Grande do Norte, Natal, Brazil.; Infectious Diseases Service, Giselda Trigueiro Hospital and Instituto de Medicina Tropical do Rio Grande do Norte, Natal, Brazil., Adenis A; Centre d'Investigation Clinique Antilles Guyane Inserm CIC1424, Centre Hospitalier de Cayenne, Cayenne, France., Bahr NC; Division of Infectious Diseases, Department of Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA., Spec A; Division of Infectious Disease, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA., Boulware DR; Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minnesota, USA., Israelski D; International Medical Affairs, Global Patient Solutions, Gilead Sciences, San Francisco, California, USA., Chiller T; Mycotic Division, Centers for Disease Control and Prevention, Atlanta, Georgia, USA., Falci DR; Infectious Diseases Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.; Department of Clinical Medicine, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.
Jazyk:	angličtina
Zdroj:	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America [Clin Infect Dis] 2023 Oct 13; Vol. 77 (8), pp. 1126-1132.
DOI:	10.1093/cid/ciad313
Abstrakt:	Background: Histoplasmosis is a major AIDS-defining illness in Latin America. Liposomal amphotericin B (L-AmB) is the drug of choice for treatment, but access is restricted due to the high drug and hospitalization costs of the conventional long regimens. Methods: Prospective randomized multicenter open-label trial of 1- or 2-dose induction therapy with L-AmB versus control for disseminated histoplasmosis in AIDS, followed by oral itraconazole therapy. We randomized subjects to: (i) single dose 10 mg/kg of L-AmB; (ii) 10 mg/kg of L-AmB on D1, and 5 mg/kg of L-AmB on D3; (iii) 3 mg/kg of L-AmB daily for 2 weeks (control). The primary outcome was clinical response (resolution of fever and signs/symptoms attributable to histoplasmosis) at day 14. Results: A total of 118 subjects were randomized, and median CD4+ counts, and clinical presentations were similar between arms. Infusion-related toxicity, kidney toxicity at multiple time-points, and frequency of anemia, hypokalemia, hypomagnesemia, and liver toxicity were similar. Day 14 clinical response was 84% for single-dose L-AmB, 69% 2-dose L-AmB, and 74% for control arm (P = .69). Overall survival on D14 was 89.0% (34/38) for single-dose L-AmB, 78.0% (29/37) for 2-dose L-AmB, and 92.1% (35/38) for control arm (P = .82). Conclusions: One day induction therapy with 10 mg/kg of L-AmB in AIDS-related histoplasmosis was safe. Although clinical response may be non-inferior to standard L-AmB therapy, a confirmatory phase III clinical trial is needed. A single induction dose would markedly reduce drug-acquisition costs (>4-fold) and markedly shorten and simplify treatment, which are key points in terms of increased access. Competing Interests: Potential conflicts of interest. A. C. P. has received research grants from Gilead, Pfizer, and IMMY (who also provided diagnostic tests for the study); he reports travel support from Pfizer, United Medical, and Merck; participation on a Data Safety Monitoring or Advisory Board for Gilead; and payment or honoraria for talks on behalf of Gilead, United Medical, Pfizer, Merck, Sharp & Dohme (MSD), IMMY, Astra-Zeneca, and Astellas Pharma. D. R. F. has received research grants and consulting fees from Pfizer, MSD, and Gilead Sciences. D. R. F. also reports travel support from Pfizer, United Medical, Janssen, and Merck; participation on Data Safety Monitoring or Advisory Boards for Gilead Sciences, Merck, and GlaxoSmithKline (GSK); has given paid lectures on behalf of United Medical, Pfizer, Janssen, GSK, Merck, Gilead Sciences, Knight Pharmaceuticals, and MSD, and received non-financial research support from IMMY. N. C. B. reports grants from National Institutes of Health (NIH) (grant numbers NINDS K23 NS110470 and NIAID R01 AI170158) and Karyopharm therapeutics (Site PI for 2020 clinical trial; funds paid to institution); and participation as chair of the Data and Safety Monitoring Board (DSMB) for NCT04335123. A. S. reports grants from Astellas and Mayne, and consulting fees from GSK and F2G. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
Databáze:	MEDLINE
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