Evidence map›Paper›PMID 26349818›Full record

Trial reportAntimicrobial agents and chemotherapy2015

Toxicity of Amphotericin B Deoxycholate-Based Induction Therapy in Patients with HIV-Associated Cryptococcal Meningitis.

Tihana Bicanic, Christian Bottomley, Angela Loyse, Annemarie E Brouwer, Conrad Muzoora, Kabanda Taseera, Arthur Jackson, Jacob Phulusa, Mina C Hosseinipour, Charles van der Horst and 7 more

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IIMulticenter Study
In one paragraph

Trial report in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06926569 (Single High-dose of Liposomal Amphotericin B in Combination With B/F/TAF for HIV/AIDS-associated Talaromycosis), which is not on this map. Cited by 70 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed, 6 pooled it
8.1field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06926569 nanot yet recruitingnot on this mapstarted 2025, after this paper: background citation

Single High-dose of Liposomal Amphotericin B in Combination With B/F/TAF for HIV/AIDS-associated Talaromycosis

TypeinterventionalSponsorShanghai Public Health Clinical CenterRan2025 to 2026Enrolled116ConditionsHIV/AIDS-associated TalaromycosisArmsAmphotericin B, AmBisome
3 · Its place in the literature

Who cites it

70 citing papers in PubMed, 6 syntheses or guidelines pooled it, 115 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Treatment for HIV-associated cryptococcal meningitis.The Cochrane database of systematic reviews · 2018
    Pooled it
  5. Pooled it
  6. Pooled it
  7. Single High Dose of Liposomal Amphotericin B in Human Immunodeficiency Virus/AIDS-Related Disseminated Histoplasmosis: A Randomized Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023
    Trial
  8. Trial
  9. Short-course High-dose Liposomal Amphotericin B for Human Immunodeficiency Virus-associated Cryptococcal Meningitis: A Phase 2 Randomized Controlled Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019
    Trial
  10. Article
  11. Article
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  13. Article
  14. Article
  15. Review
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  20. Review

10 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 10 institutions in 7 countries.

Tihana BicanicInstitute of Infection and Immunity, St. George's University of London, London, United Kingdom tbicanic@sgul.ac.uk.
Christian BottomleyFaculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Angela LoyseInstitute of Infection and Immunity, St. George's University of London, London, United Kingdom.
Annemarie E BrouwerElisabeth Hospital, Tilburg, the Netherlands.
Conrad MuzooraMbarara University of Science and Technology, Mbarara, Uganda.
Kabanda TaseeraMbarara University of Science and Technology, Mbarara, Uganda.
Arthur JacksonUniversity of North Carolina Project, Lilongwe, Malawi.
Jacob PhulusaUniversity of North Carolina Project, Lilongwe, Malawi.
Mina C HosseinipourUniversity of North Carolina Project, Lilongwe, Malawi.
Charles van der HorstUniversity of North Carolina Project, Lilongwe, Malawi.
Direk LimmathurotsakulMahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Nicholas J WhiteMahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
Douglas WilsonEdendale Hospital, Pietermaritzburg, South Africa.
Robin WoodDesmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
Graeme MeintjesDivision of Infectious Diseases and HIV Medicine, Department of Medicine, University of Cape Town, Cape Town, South Africa Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
Thomas S HarrisonInstitute of Infection and Immunity, St. George's University of London, London, United Kingdom.
Joseph N JarvisDepartment of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom Botswana-UPenn Partnership, Gaborone, Botswana Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
St George's, University of London · GBMbarara University of Science and Technology · UGBotswana Open University · BWDesmond Tutu HIV Foundation · ZAEdendale Hospital · ZAElisabeth-TweeSteden Ziekenhuis · NLLondon School of Hygiene & Tropical Medicine · GBMahidol Oxford Tropical Medicine Research Unit · THUniversity of Cape Town · ZAUniversity of Oxford · GB

Funding

Virus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI DAVID S METZGER · 1999 to 2026
$78.6M
Virology, Immunology, and Microbiology CoreP30AI050410 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DAVID M. MARGOLIS · 2001 to 2026
$76.9M
AIDS INTERNATIONAL TRAINING AND RESEARCH PROGRAMD43TW001039 · FIC · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ADIMORA, ADAORA A · 1998 to 2013
$9.9M
FIC NIH HHS 2-D43 TW01039FIC NIH HHS D43 TW001039Medical Research Council G0501476Medical Research Council MR/K012126/1NIAID NIH HHS P30 AI045008NIAID NIH HHS P30 AI050410NIAID NIH HHS P30-AI50410Wellcome Trust 093956Wellcome Trust 098316Wellcome Trust WT 081794Wellcome Trust WT 089966
6 · The paper itself

Abstract

Amphotericin B deoxycholate (AmBd) is the recommended induction treatment for HIV-associated cryptococcal meningitis (CM). Its use is hampered by toxicities that include electrolyte abnormalities, nephrotoxicity, and anemia. Protocols to minimize toxicity are applied inconsistently. In a clinical trial cohort of AmBd-based CM induction treatment, a standardized protocol of preemptive hydration and electrolyte supplementation was applied. Changes in blood counts, electrolyte levels, and creatinine levels over 14 days were analyzed in relation to the AmBd dose, treatment duration (short course of 5 to 7 days or standard course of 14 days), addition of flucytosine (5FC), and outcome. In the 368 patients studied, the hemoglobin levels dropped by a mean of 1.5 g/dl (95% confidence interval [CI], 1.0 to 1.9 g/dl) following 7 days of AmBd and by a mean of 2.3 g/dl (95% CI, 1.1 to 3.6 g/dl) after 14 days. Serum creatinine levels increased by 37 μmol/liter (95% CI, 30 to 45 μmol/liter) by day 7 and by 49 μmol/liter (95% CI, 35 to 64μmol/liter) by day 14 of AmBd treatment. Overall, 33% of patients developed grade III/IV anemia, 5.6% developed grade III hypokalemia, 9.5% had creatinine levels that exceeded 220 μmol, and 6% discontinued AmBd prematurely. The addition of 5FC was associated with a slight increase in anemia but not neutropenia. Laboratory abnormalities stabilized or reversed during the second week in patients on short-course induction. Grade III/IV anemia (adjusted odds ratio [aOR], 2.2; 95% CI, 1.1 to 4.3; P = 0.028) and nephrotoxicity (aOR, 4.5; 95% CI, 1.8 to 11; P = 0.001) were risk factors for 10-week mortality. In summary, routine intravenous saline hydration and preemptive electrolyte replacement during AmBd-based induction regimens for HIV-associated CM minimized the incidence of hypokalemia and nephrotoxicity. Anemia remained a concerning adverse effect. The addition of flucytosine was not associated with increased neutropenia. Shorter AmBd courses were less toxic, with rapid reversibility.

Indexed as

AdultAmphotericin BAnemiaAntifungal AgentsBlood Cell CountCoinfectionCreatinineCryptococcus neoformansDeoxycholic AcidDrug CombinationsFemaleFlucytosineHemoglobinsHIVHIV InfectionsHumansAmphotericin Bamphotericin B, deoxycholate drug combinationAntifungal AgentsCreatinineDeoxycholic AcidDrug CombinationsFlucytosineHemoglobins

Identifiers

PMID26349818
PMCPMC4649151
OpenAlexW2227875810

What OpenQuestion holds

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LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.