Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2023 Oct 13;77(8):1126-1132.
doi: 10.1093/cid/ciad313.

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

Alessandro C Pasqualotto  1   2 , Daiane Dalla Lana  1 , Cassia S M Godoy  3   4 , Terezinha do Menino Jesus Silva Leitão  5   6 , Monica B Bay  7   8 , Lisandra Serra Damasceno  5   6 , Renata B A Soares  3   4 , Roger Kist  2 , Larissa R Silva  1 , Denusa Wiltgen  1   2 , Marineide Melo  9 , Taiguara F Guimarães  3 , Marilia R Guimarães  10 , Hareton T Vechi  7 , Jacó R L de Mesquita  5 , Gloria Regina de G Monteiro  7   8 , Antoine Adenis  11 , Nathan C Bahr  12 , Andrej Spec  13 , David R Boulware  14 , Dennis Israelski  15 , Tom Chiller  16 , Diego R Falci  17   18
Affiliations
Randomized Controlled Trial

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

Alessandro C Pasqualotto et al. Clin Infect Dis. .

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.

Trial registration: ClinicalTrials.gov NCT05814432.

Keywords: AIDS; HIV; disseminated histoplasmosis; liposomal amphotericin B; treatment.

PubMed Disclaimer

Conflict of interest statement

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.

Figures

Graphical Abstract
Graphical Abstract
This graphical abstract is also available at Tidbit https://tidbitapp.io/tidbits/single-high-dose-of-liposomal-amphotericin-b-in-hiv-aids-related-disseminated-histoplasmosisa-randomized-trial
Figure 1.
Figure 1.
Randomization process.
Figure 2.
Figure 2.
Cumulative survival per study arm. Arm 1 received single (10 mg/kg) high dose of lipossomal amphotericin B (n = 40). Arm 2 received 10 mg/kg on day 1, followed by 5 mg/kg on day 3 (n = 39). Arm 3 is the control group (3 mg/kg of liposomal amphotericin B for 2 weeks) (n = 39).
Figure 3.
Figure 3.
Kidney and liver toxicities per study arm on days 7 and 14 of study. Arm 1 received single (10 mg/kg) high dose of lipossomal amphotericin B (n = 40). Arm 2 received 10 mg/kg on day 1, followed by 5 mg/kg on day 3 (n = 39). Arm 3 is the control group (3 mg/kg of liposomal amphotericin B for 2 weeks) (n = 39).
See this image and copyright information in PMC

References

    1. Adenis AA, Valdes A, Cropet C, et al. Burden of HIV-associated histoplasmosis compared with tuberculosis in Latin America: a modelling study. Lancet Infect Dis 2018; 18:1150–9. - PMC - PubMed
    1. Falci DR, Pasqualotto AC. Clinical mycology in Latin America and the Caribbean: a snapshot of diagnostic and therapeutic capabilities. Mycoses 2019; 62:368–73. - PubMed
    1. Pasqualotto AC, Quieroz-Telles F. Histoplasmosis dethrones tuberculosis in Latin America. Lancet Infect Dis 2018; 18:1058–60. - PubMed
    1. Nacher M, Couppié P, Epelboin L, Djossou F, Demar M, Adenis A. Disseminated histoplasmosis: fighting a neglected killer of patients with advanced HIV disease in Latin America. PLoS Pathog 2020; 16:e1008449. - PMC - PubMed
    1. Hung CC, Banerjee S, Gilada I, et al. Impact of COVID-19 on the HIV care continuum in Asia: insights from people living with HIV, key populations, and HIV healthcare providers. PLoS One 2022; 17:e0270831. - PMC - PubMed

Publication types

MeSH terms

Associated data

LinkOut - more resources