Abstract
BackgroundCurrent 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.MethodWe 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.ResultsThe 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).ConclusionsIn 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.
Highlights
Current World Health Organization (WHO) guidelines (2018) recommend screening for cryptococcal antigen (CrAg) in Human immunodeficiency virus (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
In our meta-analysis the incidence of Cryptococcal meningitis (CM) was significantly reduced by pre-emptive antifungal therapy in CrAg+ HIV-infected persons with CD4 < 200 cells/μL
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
Summary
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 be considered for those persons with a CD4+ T cell count of < 200 cells/uL according the WHO guidelines. It is possible to detect cryptococcal antigen (CrAg) in blood several weeks to months (22 days on average) before the onset of signs and symptoms of meningitis [4, 5], and the presence of CrAg in blood may be used as a marker for initiation of pre-emptive antifungal therapy in HIV-infected individuals with low CD4+ T cell counts. CrAg positivity resulted in a 20% increase in mortality after antiretroviral therapy (ART) initiation [10] if fluconazole therapy was not initiated prior to ART initiation, and the risk of CM in CrAg+ persons may be as high as 25% during the first year of ART, when fluconazole pre-emptive therapy is not prescribed for these patients [11, 12]
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