HIV-Associated Cryptococcal Meningitis: A Call for Action for New Treatment Options

  1. Samuel Okurut
  2. David B. Meya

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Abstract

Cryptococcal meningitis occurs in 62% of persons with HIV-associated meningitis, making Cryptococcus an important cause of meningitis among adults with advanced HIV disease in regions with elevated prevalence of HIV. Despite efforts to advance treatment, the in-hospital death rate of 19% remains unprecedentedly high. Aggregate published clinical trial data evaluating cryptococcosis treatment with survival as the primary endpoint show a significant reduction in the proportion of survivors from diagnosis to 88.5% at 2 weeks of treatment and further to 74% survival at 10 weeks of follow-up (p = 0.001). Disease complications concomitant with unveiling symptoms and reoccurrence of fungal infections, deferment in treatment, and high prevalence of other comorbidities increase the risk of individuals succumbing to cryptococcal meningitis. Among clinical trials of cryptococcal meningitis, the World Health Organization-recommended standard of care was used to randomize participants to the control trial arm. The proportion of participants surviving in the trial was not statistically different between trial randomization arms. In summary, high in-hospital death rates and continued participants’ deterioration post-hospital discharge are challenges for evidence-based new therapies seeking to improve outcomes.

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  1. Version published to 10.3390/therapeutics3020009
  2. PREreview

    This Zenodo record is a permanently preserved version of a Structured PREreview. You can view the complete PREreview at https://prereview.org/reviews/18444011.

    Does the introduction explain the objective of the research presented in the preprint? Yes Yes, the introduction clearly explained the objective of the study with supported evidence.
    Are the methods well-suited for this research? Highly appropriate Yes, except for the omission of the subheading of the methodology.
    Are the conclusions supported by the data? Highly supported Yes, the conclusions were realistic and supported by the data.
    Are the data presentations, including visualizations, well-suited to represent the data? Highly appropriate and clear The data and results were clearly presented and are consistent with the study's findings.
    How clearly do the authors discuss, explain, and interpret their findings and potential next steps for the research? Very clearly The findings were coherently articulated, with clear implications for future research."
    Is the preprint likely to advance academic knowledge? Highly likely The preprint contributed additional perspectives on disease management.
    Would it benefit from language editing? No The language is easy to comprehend.
    Would you recommend this preprint to others? Yes, it's of high quality Apart from adding subheadings to the methodology section, no further revisions are required.
    Is it ready for attention from an editor, publisher or broader audience? Yes, as it is The authors were consistent with their review from the beginning to the end.

    Competing interests

    The author declares that they have no competing interests.

    Use of Artificial Intelligence (AI)

    The author declares that they did not use generative AI to come up with new ideas for their review.

  3. Version published to 10.20944/preprints202512.2263.v2
  4. Version published to 10.20944/preprints202512.2263.v1