TY - JOUR
T1 - Single High Dose of Liposomal Amphotericin B in Human Immunodeficiency Virus/AIDS-Related Disseminated Histoplasmosis
T2 - A Randomized Trial
AU - Pasqualotto, Alessandro C.
AU - Lana, Daiane Dalla
AU - Godoy, Cassia S.M.
AU - Leitão, Terezinha Do Menino Jesus Silva
AU - Bay, Monica B.
AU - Damasceno, Lisandra Serra
AU - Soares, Renata B.A.
AU - Kist, Roger
AU - Silva, Larissa R.
AU - Wiltgen, Denusa
AU - Melo, Marineide
AU - Guimarães, Taiguara F.
AU - Guimarães, Marilia R.
AU - Vechi, Hareton T.
AU - De Mesquita, Jacó R.L.
AU - Monteiro, Gloria Regina De G.
AU - Adenis, Antoine
AU - Bahr, Nathan C.
AU - Spec, Andrej
AU - Boulware, David R.
AU - Israelski, Dennis
AU - Chiller, Tom
AU - Falci, Diego R.
N1 - Publisher Copyright:
© 2023 The Author(s). Published by Oxford University Press on behalf of Infectious Diseases Society of America.
PY - 2023/10/15
Y1 - 2023/10/15
N2 - 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.
AB - 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.
KW - AIDS
KW - HIV
KW - disseminated histoplasmosis
KW - liposomal amphotericin B
KW - treatment
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UR - http://www.scopus.com/inward/citedby.url?scp=85170503828&partnerID=8YFLogxK
U2 - 10.1093/cid/ciad313
DO - 10.1093/cid/ciad313
M3 - Article
C2 - 37232940
AN - SCOPUS:85170503828
SN - 1058-4838
VL - 77
SP - 1126
EP - 1132
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 8
ER -