Evidence map›Paper›PMID 29945252›Full record

Trial reportClinical infectious diseases : an official publication of the Infectious Diseases Society of America2019

Short-course High-dose Liposomal Amphotericin B for Human Immunodeficiency Virus-associated Cryptococcal Meningitis: A Phase 2 Randomized Controlled Trial.

Joseph N Jarvis, Tshepo B Leeme, Mooketsi Molefi, Awilly A Chofle, Gabriella Bidwell, Katlego Tsholo, Nametso Tlhako, Norah Mawoko, Raju K K Patel, Mark W Tenforde and 9 more

Open access · bronzeAbstract readClinical Trial, Phase IIRandomized Controlled TrialEquivalence Trial
In one paragraph

Trial report in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 6 pooled it
7.8field-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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

48 citing papers in PubMed, 6 syntheses or guidelines pooled it, 77 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Treatment for HIV-associated cryptococcal meningitis.The Cochrane database of systematic reviews · 2018
    Pooled it
  7. Trial
  8. How Applicable Is the Single-Dose AMBITION Regimen for Human Immunodeficiency Virus-Associated Cryptococcal Meningitis to High-Income Settings?Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023
    Trial
  9. Trial
  10. Article
  11. Article
  12. Review
  13. Review
  14. Optimizing antifungal dosing for invasiveFrontiers in pharmacology · 2025
    Article
  15. Article
  16. Article
  17. Review
  18. Amphotericin B in the Era of New Antifungals: Where Will It Stand?Journal of fungi (Basel, Switzerland) · 2024
    Review
  19. Review
  20. Article
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

19 authors at 7 institutions in 4 countries.

Joseph N JarvisBotswana-University of Pennsylvania Partnership, Gaborone.
Tshepo B LeemeBotswana-University of Pennsylvania Partnership, Gaborone.
Mooketsi MolefiUniversity of Botswana, Gaborone.
Awilly A ChofleNational Institute of Medical Research, Mwanza, Tanzania.
Gabriella BidwellNational Institute of Medical Research, Mwanza, Tanzania.
Katlego TsholoBotswana-University of Pennsylvania Partnership, Gaborone.
Nametso TlhakoBotswana-University of Pennsylvania Partnership, Gaborone.
Norah MawokoBotswana-University of Pennsylvania Partnership, Gaborone.
Raju K K PatelBotswana-University of Pennsylvania Partnership, Gaborone.
Mark W TenfordeBotswana-University of Pennsylvania Partnership, Gaborone.
Charles MuthogaBotswana-University of Pennsylvania Partnership, Gaborone.
Gregory P BissonDivision of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
Jeremiah KidolaNational Institute of Medical Research, Mwanza, Tanzania.
John ChangaluchaNational Institute of Medical Research, Mwanza, Tanzania.
David LawrenceDepartment of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom.
Shabbar JaffarDepartment of International Public Health, Liverpool School of Tropical Medicine, United Kingdom.
William HopeAntimicrobial Pharmacodynamics and Therapeutics, Department of Molecular and Clinical Pharmacology, University of Liverpool, United Kingdom.
Si le F MolloyCentre for Global Health, Institute for Infection and Immunity, St George's University of London, United Kingdom.
Thomas S HarrisonCentre for Global Health, Institute for Infection and Immunity, St George's University of London, United Kingdom.
University of Botswana · BWNational Institute for Medical Research · TZSt George's, University of London · GBLiverpool School of Tropical Medicine · GBLondon School of Hygiene & Tropical Medicine · GBUniversity of Liverpool · GBUniversity of Pennsylvania · US

Funding

Virus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI DAVID S METZGER · 1999 to 2026
$78.6M
HOST DEFENSE TRAINING IN ALLERGY AND INFECTIOUS DISEASEST32AI007044 · NIAID · UNIVERSITY OF WASHINGTON · PI DAVID Neal FREDRICKS · 1985 to 2026
$14.6M
Medical Research Council G1001760Medical Research Council MC_PC_MR/P006922/1Medical Research Council MR/N023005/1NIAID NIH HHS P30 AI045008NIAID NIH HHS T32 AI007044
6 · The paper itself

Abstract

Background: We performed a phase 2 noninferiority trial examining the early fungicidal activity (EFA) of 3 short-course, high-dose liposomal amphotericin B (L-AmB) regimens for cryptococcal meningitis (CM) in Tanzania and Botswana. Methods: Human immunodeficiency virus (HIV)-infected adults with CM were randomized to (i) L-AmB 10 mg/kg on day 1 (single dose); (ii) L-AmB 10 mg/kg on day 1 and 5 mg/kg on day 3 (2 doses); (iii) L-AmB 10 mg/kg on day 1 and 5 mg/kg on days 3 and 7 (3 doses); or (iv) L-AmB 3 mg/kg/day for 14 days (control). All patients also received oral fluconazole 1200 mg/day for 14 days. Primary endpoint was mean rate of clearance of cerebrospinal fluid cryptococcal infection (EFA). Noninferiority was defined as an upper limit of the 2-sided 95% confidence interval (CI) of difference in EFA between intervention and control <0.2 log10 colony-forming units (CFU)/mL/day. Results: Eighty participants were enrolled. EFA for daily L-AmB was -0.41 log10 CFU/mL/day (standard deviation, 0.11; n = 17). Difference in mean EFA from control was -0.11 (95% CI, -.29 to .07) log10 CFU/mL/day faster with single dose (n = 16); -0.05 (95% CI, -.20 to .10) log10 CFU/mL/day faster with 2 doses (n = 18); and -0.13 (95% CI, -.35 to .09) log10 CFU/mL/day faster with 3 doses (n = 18). EFA in all short-course arms was noninferior to control. Ten-week mortality was 29% (n = 23) with no statistical difference between arms. All arms were well tolerated. Conclusions: Single-dose 10 mg/kg L-AmB was well tolerated and led to noninferior EFA compared to 14 days of 3 mg/kg/day L-AmB in HIV-associated CM. Induction based on a single 10 mg/kg L-AmB dose is being taken forward to a phase 3 clinical endpoint trial. Clinical Trials Registration: ISRCTN 10248064.

Indexed as

AdultAmphotericin BAntifungal AgentsBotswanaCerebrospinal FluidCryptococcus neoformansFemaleHIV InfectionsHumansMaleMeningitis, CryptococcalTanzaniaTreatment OutcomeAmphotericin BAntifungal Agentsliposomal amphotericin B

Identifiers

PMID29945252
PMCPMC6336908
OpenAlexW2809879222

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.