Primary Prophylaxis for Cryptococcal Meningitis and Impact on Mortality in HIV: A Systematic Review and Meta-Analysis

Abstract

Aim: To determine the role of primary antifungal prophylaxis in the prevention of cryptococcal meningitis and all-cause mortality in advanced HIV infection. Materials & methods: This was a systematic review and meta-analysis of randomized trials and observational studies. Google Scholar™, PubMed and Embase databases were searched for relevant studies. Quality was assessed using different criteria, depending on study type. Publication bias was assessed and subgroup and sensitivity analyses were performed. When the results of the meta-analysis were homogeneous, the fixed-effects model was used; when the results of the meta-analysis were heterogenous, the random effects model was used. Results: Primary prophylaxis prevented cryptococcal meningitis but did not confer protection against overall mortality, although there was evidence of a reduction in cryptococcal-specific mortality in resource-limited settings. Conclusion: Primary antifungal prophylaxis should be recommended in patients with advanced HIV infection in resource-limited settings with a high incidence of cryptococcal meningitis.

Keywords:

• advanced HIV infection
• all-cause mortality
• cryptococcal meningitis
• fluconazole
• itraconazole
• prevention of cryptococcal meningitis
• primary antifungal prophylaxis
• resource-limited settings

Author contributions

Concept development: R Ssekitoleko, MR Kamya and AL Reingold. Data collection: R Ssekitoleko. Supervision of the study: MR Kamya and AL Reingold. Data interpretation and revision of all the drafts: R Ssekitoleko, MR Kamya and AL Reingold. All authors read and approved the final manuscript.

Acknowledgements

The authors would like to thank AH Smith and C Steinmus for guidance with the statistical analysis and K Andrews and A Nabasirye for help and guidance with the data search.

Financial & competing interests disclosure

The authors would like to thank the Forgarty AIDS International Training and Research Program (grant number: 1-D43-TW0003) for providing all support to R Ssekitoleko while studying at the School of Public Health, University of California, Berkeley. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

The authors would like to thank the Forgarty AIDS International Training and Research Program (grant number: 1-D43-TW0003) for providing all support to R Ssekitoleko while studying at the School of Public Health, University of California, Berkeley. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.