Single High-dose of Liposomal Amphotericin B in Human Immunodeficiency Virus (HIV)/AIDS-related Disseminated Histoplasmosis: A Randomized Trial

Nenhuma Miniatura disponível
Citações na Scopus
6
Tipo de produção
article
Data de publicação
2023
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
OXFORD UNIV PRESS INC
Autores
PASQUALOTTO, Alessandro C.
LANA, Daiane Dalla
GODOY, Cassia S. M.
LEITAO, Terezinha do Menino Jesus Silva
BAY, Monica B.
DAMASCENO, Lisandra Serra
SOARES, Renata B. A.
KIST, Roger
SILVA, Larissa R.
WILTGEN, Denusa
Citação
CLINICAL INFECTIOUS DISEASES, v.77, n.8, p.1126-1132, 2023
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
This is the first trial to demonstrate that AIDS patients with disseminated histoplasmosis can be safely and effectively treated with a single high dose of liposomal amphotericin B (10 mg/kg). 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.
Palavras-chave
disseminated histoplasmosis, liposomal amphotericin B, AIDS, HIV, treatment
URI
https://observatorio.fm.usp.br/handle/OPI/58213
Referências
  1. Adenis AA, 2018, LANCET INFECT DIS, V18, P1150, DOI 10.1016/S1473-3099(18)30354-2
  2. Adler-Moore J, 2019, CLIN INFECT DIS, V68, pS244, DOI 10.1093/cid/ciz064
  3. [Anonymous], 2012, KIDNEY INT SUPPL, V2, P8, DOI [DOI 10.1038/KISUP.2012.6, 10.1038/kisup.2012.7, DOI 10.1038/KISUP.2012.7]
  4. Bates DW, 2001, KIDNEY INT, V60, P1452, DOI 10.1046/j.1523-1755.2001.00948.x
  5. Araúz AB, 2021, INFECT DIS CLIN N AM, V35, P471, DOI 10.1016/j.idc.2021.03.011
  6. Bicanic T, 2015, ANTIMICROB AGENTS CH, V59, P7224, DOI 10.1128/AAC.01698-15
  7. Falci DR, 2021, LANCET REG HEALTH-AM, V3, DOI 10.1016/j.lana.2021.100037
  8. Falci DR, 2022, NEW ENGL J MED, V387, P380, DOI 10.1056/NEJMc2206274
  9. Falci DR, 2019, MYCOSES, V62, P368, DOI 10.1111/myc.12890
  10. Groll AH, 2019, CLIN INFECT DIS, V68, pS260, DOI 10.1093/cid/ciz076
  11. Hung CC., 2022, PLOS ONE, V17
  12. Jarvis JN, 2022, NEW ENGL J MED, V386, P1109, DOI 10.1056/NEJMoa2111904
  13. Johnson PC, 2002, ANN INTERN MED, V137, P105, DOI 10.7326/0003-4819-137-2-200207160-00008
  14. Luber AD, 1999, J ANTIMICROB CHEMOTH, V43, P267, DOI 10.1093/jac/43.2.267
  15. Nacher M, 2020, PLOS PATHOG, V16, DOI 10.1371/journal.ppat.1008449
  16. Pasqualotto AC, 2018, LANCET INFECT DIS, V18, P1058, DOI 10.1016/S1473-3099(18)30373-6
  17. Perez F, 2021, J FUNGI, V7, DOI 10.3390/jof7020134
  18. Personett HA, 2019, INT J NEPHROL, V2019, DOI 10.1155/2019/8629891
  19. Sayeed M, 2022, J CLIN TRANSL HEPATO, V10, P726, DOI 10.14218/JCTH.2020.00080
  20. Shigemi A, 2011, INT J ANTIMICROB AG, V38, P417, DOI 10.1016/j.ijantimicag.2011.07.004
  21. Sundar S, 2010, NEW ENGL J MED, V362, P504, DOI 10.1056/NEJMoa0903627
  22. Suresh Kp, 2011, J Hum Reprod Sci, V4, P8, DOI 10.4103/0974-1208.82352
  23. Ullmann AJ, 2008, MYCOSES, V51, P25, DOI 10.1111/j.1439-0507.2008.01525.x
  24. US Department of Health and Human Services NIoH National Institute of Allergy and Infectious Diseases Division of AIDS, 2017, DIV AIDS DAIDS TABL
  25. World Health Organization, 2022, GUID DIAGN PREV MAN

Coleções
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/12
Artigos e Materiais de Revistas Científicas - ODS/03