Background: Current WHO guidelines (2018) recommend screening for cryptococcal antigen (CrAg) in HIV+ persons with CD4<100 cells/μL, followed by pre-emptive antifungal therapy among CrAg positive (CrAg+) persons, to prevent CM-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+ 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+ 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) higher than that of CrAg negative (CrAg-) persons (1%, 95%CI: 0-1). All-cause mortality in CrAg+ persons was 15% (95%CI: 12-18), more than 1.67 times that of CrAg- persons (9%, 95%CI: 6-13). Among CrAg+ persons who did not receive any treatment or only received placebo, the incidence of CM was 9% (95%CI: 4-13), 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: 0.17, 95%CI: 0.08-0.36, p <0.00001).
Conclusions: In our meta-analysis, the incidence of CM and all-cause mortality 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. Our results suggest that the CD4 level for initiating CrAg screening and pre-emptive therapy should now definitely be raised to 200 cells/µL in these HIV-infected individuals.