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
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.
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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
Posted 13 May, 2020
On 20 May, 2020
Received 20 May, 2020
Invitations sent on 14 May, 2020
On 29 Apr, 2020
On 28 Apr, 2020
On 10 Sep, 2019
On 24 Apr, 2020
Received 20 Apr, 2020
Received 14 Apr, 2020
On 06 Apr, 2020
On 03 Apr, 2020
Invitations sent on 02 Apr, 2020
On 30 Mar, 2020
On 29 Mar, 2020
On 29 Mar, 2020
On 17 Mar, 2020
Received 07 Mar, 2020
Received 07 Mar, 2020
On 26 Feb, 2020
Invitations sent on 26 Feb, 2020
On 26 Feb, 2020
On 26 Feb, 2020
On 25 Feb, 2020
On 25 Feb, 2020
On 12 Feb, 2020
Received 10 Feb, 2020
On 04 Oct, 2019
Received 01 Oct, 2019
On 29 Sep, 2019
Invitations sent on 26 Sep, 2019
On 11 Sep, 2019
On 10 Sep, 2019
On 10 Sep, 2019
On 05 Sep, 2019
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