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

2023; Oxford University Press; Volume: 77; Issue: 8 Linguagem: Inglês

10.1093/cid/ciad313

1537-6591

Alessandro C. Pasqualotto, Daiane Dalla Lana, Cassia S M Godoy, Terezinha do Menino Jesus Silva Leitão, Mônica Baumgardt Bay, Lisandra Serra Damasceno, Renata de Bastos Ascenço Soares, Roger Kist, Larissa R. Silva, Denusa Wiltgen, Marineide Gonçalves de Melo, Taiguara F Guimarães, Marilia R Guimarães, Hareton Teixeira Vechi, Jacó Ricarte Lima de Mesquita, Gloria Regina de Góis Monteiro, Antoine Adenis, Nathan C. Bahr, Andrej Spec, David R. Boulware, Dennis Israelski, Tom Chiller, Diego R. Falci,

Research on Leishmaniasis Studies

Abstract 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.