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

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. BoulwareDennis Israelski, Tom Chiller, Diego R. Falci

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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.

Original languageEnglish
Pages (from-to)1126-1132
Number of pages7
JournalClinical Infectious Diseases
Volume77
Issue number8
DOIs
StatePublished - Oct 15 2023

Keywords

  • AIDS
  • HIV
  • disseminated histoplasmosis
  • liposomal amphotericin B
  • treatment

Fingerprint

Dive into the research topics of 'Single High Dose of Liposomal Amphotericin B in Human Immunodeficiency Virus/AIDS-Related Disseminated Histoplasmosis: A Randomized Trial'. Together they form a unique fingerprint.

Cite this