Single High-dose of Liposomal Amphotericin B in HIV/AIDS-related Disseminated Histoplasmosis: a Randomized Trial
| Autor: | Alessandro C Pasqualotto, Daiane Dalla Lana, Cassia S M Godoy, Terezinha do Menino Jesus Silva Leitão, Monica B Bay, Lisandra Serra Damasceno, Renata B A Soares, Roger Kist, Larissa R Silva, Denusa Wiltgen, Marineide Melo, Taiguara F Guimarães, Marilia R Guimarães, Hareton T Vechi, Jacó R L de Mesquita, Gloria Regina de G Monteiro, Antoine Adenis, Nathan C Bahr, Andrej Spec, David R Boulware, Dennis Israelski, Tom Chiller, Diego R Falci |
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| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Clinical Infectious Diseases. |
| ISSN: | 1537-6591 1058-4838 |
| DOI: | 10.1093/cid/ciad313 |
| Popis: | 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 one or two-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 randomizedMedian 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% Two-dose L-AmB, and 74% Control arm (p=0.69). Overall survival on D14 was 89.0% (34/38) for Single-dose L-AmB, 78.0% (29/37) for Two-dose L-AmB, and 92.1% (35/38) for Control arm (p=0.82). 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. |
| Databáze: | OpenAIRE |
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