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. 2023 Apr;24(4):507-512.
doi: 10.1111/hiv.13412. Epub 2022 Sep 19.

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

Adrienne E Shapiro  1 , Mark W Tenforde  2 , Tom M Chiller  2 , Nathan Ford  3 , Radha Rajasingham  4
Affiliations

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

Adrienne E Shapiro et al. HIV Med. 2023 Apr.

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.

Keywords: AIDS; AIDS-related opportunistic infections; cryptococcal meningitis; liposomal amphotericin; systematic review.

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Conflict of interest statement

Conflict of interest disclosure: The authors have no conflicts of interest to declare.

Figures

Figure 1.
Figure 1.
Study flow diagram.
Figure 2.
Figure 2.
Forest plot comparing 2-week mortality (above) and 10-week mortality (below) between single-dose liposomal amphotericin with flucytosine and fluconazole compared to standard of care amphotericin with flucytosine and fluconazole.
See this image and copyright information in PMC

References

    1. Rajasingham R, Smith RM, Park BJ, et al. Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis. The Lancet Infectious diseases. 2017;17(8):873–881. - PMC - PubMed
    1. Tenforde MW, Shapiro AE, Rouse B, et al. Treatment for HIV-associated cryptococcal meningitis. The Cochrane database of systematic reviews. 2018;7(7):Cd005647. - PMC - PubMed
    1. World Health Organization. The Diagnosis, Prevention and Management of Cryptococcal Disease in HIV-infected adults, adolescents and children. Geneva, Switzerland: 2018. - PubMed
    1. Molloy SF, Kanyama C, Heyderman RS, et al. Antifungal Combinations for Treatment of Cryptococcal Meningitis in Africa. The New England journal of medicine. 2018;378(11):1004–1017. - PubMed
    1. Tenforde MW, Gertz AM, Lawrence DS, et al. Mortality from HIV-associated meningitis in sub-Saharan Africa: a systematic review and meta-analysis. Journal of the International AIDS Society. 2020;23(1):e25416. - PMC - PubMed

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