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The prevalence of cryptococcal antigen (CrAg) and benefits of pre-emptive antifungal treatment among HIV-infected persons with CD4+ T-cell counts < 200 cells/μL: Evidence based on a meta-analysis
Yaokai Chen
Chongqing Public Health Medical Center
Corresponding Author
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This work is licensed under a CC BY 4.0 License. Read Full License
Background: Current WHO guidelines (2018) recommend screening for cryptococcal antigen (CrAg) in HIV-infected persons with CD4+ T cell counts<100 cells/μL, followed by pre-emptive antifungal therapy among CrAg positive (CrAg+) persons, to prevent cryptococcal meningitis related deaths. This strategy may also be considered for those persons with a CD4+ T cell count of < 200 cells/uL according the WHO guidelines. However, there is sparse evidence in the literature supporting CrAg screening and pre-emptive antifungal therapy in those HIV-infected persons with this CD4+ T cell counts<200 cells/μL.
Objective: We aimed to assess the prevalence of CrAg in HIV-infected persons, and to assess the efficacy of pre-emptive antifungal therapy in CrAg+ persons with CD4+ T cell<200 cells/µL.
Methods: We conducted a meta-analysis using data extracted from randomized controlled studies (RCTs) and cohort studies found in a search of Pubmed, Web of Science, the Cochrane Library and the EMBASE/MEDLINE database.
Results: The pooled prevalence of CrAg positivity in HIV-infected persons with CD4+ T cell counts<200 cells/µL was 5% (95%CI: 2-7). The incidence of CM in CrAg+ persons was 3% (95%CI: 1-6). Among those CrAg+ persons who did not receive pre-emptive treatment, or those who received placebo, the incidence of CM was 5% (95%CI: 2-9), whereas the incidence of CM among those who received pre-emptive antifungal therapy was 3% (95%CI: 1-6), which is a statistically significant reduction in incidence of 40% (RR: 7.64, 95%CI: 2.96-19.73, p <0.00001). As for persons with CD4+ T cell counts between 101~200 cells/µL, the risk ratio for the incidence of CM among those receiving placebo or no intervention was 1.15, compared to those receiving antifungal treatment (95%CI: 0.16-8.13).
Conclusions: In our meta-analysis the incidence of CM was significantly reduced by pre-emptive antifungal therapy in CrAg+ HIV-infected persons with CD4<200 cells/µL. However, more specific observational data in persons with CD4+ T cell counts between 101~200 cells/µL are required in order to emphasize specific benefit of CrAg screening and pre-emptive antifungal treating in CrAg+ persons with CD4+ T cell counts <200 cells/µL.
Keywords
HIV, cryptococcal antigenemia, screening, CD4+T cell count, pre-emptive treatment, meta-analysis
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CURRENT STATUS: Under Review
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Posted 13 May, 2020
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Reviewer #1 agreed
On 20 May, 2020
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Received 20 May, 2020
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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
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
The prevalence of cryptococcal antigen (CrAg) and benefits of pre-emptive antifungal treatment among HIV-infected persons with CD4+ T-cell counts < 200 cells/μL: Evidence based on a meta-analysis
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
Version 4
Posted 13 May, 2020
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
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
Background: Current WHO guidelines (2018) recommend screening for cryptococcal antigen (CrAg) in HIV-infected persons with CD4+ T cell counts<100 cells/μL, followed by pre-emptive antifungal therapy among CrAg positive (CrAg+) persons, to prevent cryptococcal meningitis related deaths. This strategy may also be considered for those persons with a CD4+ T cell count of < 200 cells/uL according the WHO guidelines. However, there is sparse evidence in the literature supporting CrAg screening and pre-emptive antifungal therapy in those HIV-infected persons with this CD4+ T cell counts<200 cells/μL.
Objective: We aimed to assess the prevalence of CrAg in HIV-infected persons, and to assess the efficacy of pre-emptive antifungal therapy in CrAg+ persons with CD4+ T cell<200 cells/µL.
Methods: We conducted a meta-analysis using data extracted from randomized controlled studies (RCTs) and cohort studies found in a search of Pubmed, Web of Science, the Cochrane Library and the EMBASE/MEDLINE database.
Results: The pooled prevalence of CrAg positivity in HIV-infected persons with CD4+ T cell counts<200 cells/µL was 5% (95%CI: 2-7). The incidence of CM in CrAg+ persons was 3% (95%CI: 1-6). Among those CrAg+ persons who did not receive pre-emptive treatment, or those who received placebo, the incidence of CM was 5% (95%CI: 2-9), whereas the incidence of CM among those who received pre-emptive antifungal therapy was 3% (95%CI: 1-6), which is a statistically significant reduction in incidence of 40% (RR: 7.64, 95%CI: 2.96-19.73, p <0.00001). As for persons with CD4+ T cell counts between 101~200 cells/µL, the risk ratio for the incidence of CM among those receiving placebo or no intervention was 1.15, compared to those receiving antifungal treatment (95%CI: 0.16-8.13).
Conclusions: In our meta-analysis the incidence of CM was significantly reduced by pre-emptive antifungal therapy in CrAg+ HIV-infected persons with CD4<200 cells/µL. However, more specific observational data in persons with CD4+ T cell counts between 101~200 cells/µL are required in order to emphasize specific benefit of CrAg screening and pre-emptive antifungal treating in CrAg+ persons with CD4+ T cell counts <200 cells/µL.
Figure 1
Figure 2
Figure 3
Figure 4