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Review
Yaokai Chen
Chongqing Public Health Medical Center
Corresponding Author
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Background: Current WHO guidelines (2018) recommend screening for cryptococcal antigen (CrAg) in HIV-infected persons with CD4<100 cells/μL, followed by pre-emptive antifungal therapy among CrAg positive (CrAg+) persons, to prevent Cryptococcal meningitis related deaths. The strategy may also be considered for those persons with a CD4 count of<200 cells/uL according the WHO guidelines. However, there remains little evidence for doing so in those HIV-infected persons with this CD4 cell count.
Objective: We aimed to assess the necessity of CrAg screening and the efficacy of pre-emptive antifungal therapy in CrAg+ persons with CD4<200 cells/µL.
Methods: We conducted a meta-analysis using data obtained from randomized controlled studies (RCTs) and cohort studies found in Pubmed, Web of Science, Cochrane Library and EMBASE/MEDLINE.
Results: The pooled prevalence of CrAg positivity in HIV-infected persons with CD4<200 cells/µL was 5% (95%CI: 3-6). The incidence of CM in CrAg+ persons was 7- fold (7%, 95%CI: 4-10) that of CrAg negative (CrAg-) persons (1%, 95%CI: 0-1). Among CrAg+ persons who did not receive any treatment or only received placebo, the incidence of CM was 9% (95%CI: 5-13), whereas the incidence of CM among those who received antifungal therapy was 2% (95%CI: 0-3), a highly statistically significant reduction of 78% (RR: 6.03, 95%CI: 2.74-13.24, p<0.00001).
Conclusions: In our meta-analysis, the incidence of CM in CrAg+ persons were significantly higher than in CrAg- persons with CD4<200 cells/µL. Furthermore, the incidence of CM was significantly reduced by pre-emptive antifungal therapy in CrAg+ persons with CD4<200 cells/µL.
Keywords
HIV, cryptococcal antigenemia, CD4, pre-emptive treatment, meta
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CURRENT STATUS: Under Review
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Reviewer #1 agreed
On 20 May, 2020
Review #1 received
Received 20 May, 2020
Reviewers invited
Invitations sent on 14 May, 2020
Editor assigned
On 29 Apr, 2020
Editor invited
On 28 Apr, 2020
Submission checks complete
On 10 Sep, 2019
No comments provided
Editorial decision: Minor revision
On 24 Apr, 2020
Review #1 received
Received 20 Apr, 2020
Review #2 received
Received 14 Apr, 2020
Reviewer #2 agreed
On 06 Apr, 2020
Reviewer #1 agreed
On 03 Apr, 2020
Reviewers invited
Invitations sent on 02 Apr, 2020
Editor assigned
On 30 Mar, 2020
Submission checks complete
On 29 Mar, 2020
Editor invited
On 29 Mar, 2020
Version 2
Posted 26 Feb, 2020
No comments provided
Editorial decision: Major revision
On 17 Mar, 2020
Review #1 received
Received 07 Mar, 2020
Review #2 received
Received 07 Mar, 2020
Editor assigned
On 26 Feb, 2020
Reviewers invited
Invitations sent on 26 Feb, 2020
Reviewer #1 agreed
On 26 Feb, 2020
Reviewer #2 agreed
On 26 Feb, 2020
Submission checks complete
On 25 Feb, 2020
Editor invited
On 25 Feb, 2020
No comments provided
Editorial decision: Major revision
On 12 Feb, 2020
Review #2 received
Received 10 Feb, 2020
Reviewer #2 agreed
On 04 Oct, 2019
Review #1 received
Received 01 Oct, 2019
Reviewer #1 agreed
On 29 Sep, 2019
Reviewers invited
Invitations sent on 26 Sep, 2019
Editor assigned
On 11 Sep, 2019
Submission checks complete
On 10 Sep, 2019
Editor invited
On 10 Sep, 2019
First submitted
On 05 Sep, 2019
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Subject Areas
Infectious Diseases
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This preprint is under consideration at BMC Infectious Diseases. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Review
Yaokai Chen
Chongqing Public Health Medical Center
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
No community comments so far
Reviewer #1 agreed
On 20 May, 2020
Review #1 received
Received 20 May, 2020
Reviewers invited
Invitations sent on 14 May, 2020
Editor assigned
On 29 Apr, 2020
Editor invited
On 28 Apr, 2020
Submission checks complete
On 10 Sep, 2019
No comments provided
Editorial decision: Minor revision
On 24 Apr, 2020
Review #1 received
Received 20 Apr, 2020
Review #2 received
Received 14 Apr, 2020
Reviewer #2 agreed
On 06 Apr, 2020
Reviewer #1 agreed
On 03 Apr, 2020
Reviewers invited
Invitations sent on 02 Apr, 2020
Editor assigned
On 30 Mar, 2020
Submission checks complete
On 29 Mar, 2020
Editor invited
On 29 Mar, 2020
Version 2
Posted 26 Feb, 2020
No comments provided
Editorial decision: Major revision
On 17 Mar, 2020
Review #1 received
Received 07 Mar, 2020
Review #2 received
Received 07 Mar, 2020
Editor assigned
On 26 Feb, 2020
Reviewers invited
Invitations sent on 26 Feb, 2020
Reviewer #1 agreed
On 26 Feb, 2020
Reviewer #2 agreed
On 26 Feb, 2020
Submission checks complete
On 25 Feb, 2020
Editor invited
On 25 Feb, 2020
No comments provided
Editorial decision: Major revision
On 12 Feb, 2020
Review #2 received
Received 10 Feb, 2020
Reviewer #2 agreed
On 04 Oct, 2019
Review #1 received
Received 01 Oct, 2019
Reviewer #1 agreed
On 29 Sep, 2019
Reviewers invited
Invitations sent on 26 Sep, 2019
Editor assigned
On 11 Sep, 2019
Submission checks complete
On 10 Sep, 2019
Editor invited
On 10 Sep, 2019
First submitted
On 05 Sep, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Infectious Diseases
License:
This work is licensed under a CC BY 4.0 License. Read Full License
The most recent version of this article is available here.
Background: Current WHO guidelines (2018) recommend screening for cryptococcal antigen (CrAg) in HIV-infected persons with CD4<100 cells/μL, followed by pre-emptive antifungal therapy among CrAg positive (CrAg+) persons, to prevent Cryptococcal meningitis related deaths. The strategy may also be considered for those persons with a CD4 count of<200 cells/uL according the WHO guidelines. However, there remains little evidence for doing so in those HIV-infected persons with this CD4 cell count.
Objective: We aimed to assess the necessity of CrAg screening and the efficacy of pre-emptive antifungal therapy in CrAg+ persons with CD4<200 cells/µL.
Methods: We conducted a meta-analysis using data obtained from randomized controlled studies (RCTs) and cohort studies found in Pubmed, Web of Science, Cochrane Library and EMBASE/MEDLINE.
Results: The pooled prevalence of CrAg positivity in HIV-infected persons with CD4<200 cells/µL was 5% (95%CI: 3-6). The incidence of CM in CrAg+ persons was 7- fold (7%, 95%CI: 4-10) that of CrAg negative (CrAg-) persons (1%, 95%CI: 0-1). Among CrAg+ persons who did not receive any treatment or only received placebo, the incidence of CM was 9% (95%CI: 5-13), whereas the incidence of CM among those who received antifungal therapy was 2% (95%CI: 0-3), a highly statistically significant reduction of 78% (RR: 6.03, 95%CI: 2.74-13.24, p<0.00001).
Conclusions: In our meta-analysis, the incidence of CM in CrAg+ persons were significantly higher than in CrAg- persons with CD4<200 cells/µL. Furthermore, the incidence of CM was significantly reduced by pre-emptive antifungal therapy in CrAg+ persons with CD4<200 cells/µL.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
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