An updated systematic review of HIV-associated cryptococcal meningitis treatment strategies

Adrienne E. Shapiro, Mark W. Tenforde, Tom M. Chiller, Nathan Ford, Radha Rajasingham

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: The purpose of this systematic review is to provide updated evidence on the preferred induction therapy for the treatment of HIV-associated cryptococcal meningitis considering the most recent evidence available in order to inform the need for updates to WHO guidelines.

METHODS: We searched Medline via PubMed, EMBASE, the Cochrane Library and clinicaltrials.gov for published or completed randomized clinical trials that evaluated induction treatment of first episode HIV-associated cryptococcal meningitis from 9 July 2018 (date of last search) to 1 September 2021.

RESULTS: One randomized clinical trial of 844 people with HIV-associated cryptococcal meningitis met the inclusion criteria. Participants were randomized to: (1) amphotericin deoxycholate for 7 days, with flucytosine and fluconazole (control); or (2) a single dose of liposomal amphotericin 10 mg/kg with flucytosine and fluconazole (intervention). In the intention-to-treat analysis, 10-week mortality was 24.8% [95% confidence interval (CI): 20.7-29.3%] in the single-dose liposomal amphotericin group compared with 28.7% (95% CI: 24.4-33.4%) in the control group. The absolute difference in 10-week mortality was -3.9% with an upper one-sided 95% CI of 1.2%, within the 10% pre-specified non-inferiority margin. Fewer participants had grade 3 and 4 adverse events in the intervention arm compared with the control arm (50.0% vs. 62.3%, p < 0.001).

CONCLUSIONS: In the single study included in this systematic review, single high-dose liposomal amphotericin B with flucytosine and fluconazole was non-inferior to the WHO-recommended standard of care induction therapy for HIV-associated cryptococcal meningitis, with significantly fewer adverse events.

Original languageEnglish (US)
JournalHIV Medicine
DOIs
StateAccepted/In press - 2022

Bibliographical note

Funding Information:
RR and AES are supported by the National Institute of Allergy and Infectious Diseases (RR: K23AI138851, R01AI162181; AES: K23AI140918). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Centers for Disease Control and Prevention.

Publisher Copyright:
© 2022 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.

Keywords

  • AIDS
  • AIDS-related opportunistic infections
  • cryptococcal meningitis
  • liposomal amphotericin
  • systematic review

PubMed: MeSH publication types

  • Journal Article

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