CD4 Cell Count Threshold for Cryptococcal Antigen Screening of HIV-Infected Individuals: A Systematic Review and Meta-analysis

Background. Current guidelines recommend screening all people living with human immunodefciency virus (PLHIV) who have a CD4 count =100 cells/μL for cryptococcal antigen (CrAg) to identify those patients who could beneft from preemptive fluconazole treatment prior to the onset of meningitis. We conducted a systematic review to assess the prevalence of CrAg positivity at different CD4 cell counts. Methods. We searched 4 databases and abstracts from 3 conferences up to 1 September 2017 for studies reporting prevalence of CrAg positivity according to CD4 cell count strata. Prevalence estimates were pooled using random effects models. Results. Sixty studies met our inclusion criteria. Te pooled prevalence of cryptococcal antigenemia was 6.5% (95% confdence interval [CI], 5.7%-7.3%; 54 studies) among patients with CD4 count =100 cells/μL and 2.0% (95% CI, 1.2%-2.7%; 21 studies) among patients with CD4 count 101-200 cells/μL. Twenty-one studies provided sufcient information to compare CrAg prevalence per strata; overall, 18.6% (95% CI, 15.4%-22.2%) of the CrAg-positive cases identifed at =200 cells/μL (n = 11 823) were identifed among individuals with a CD4 count 101-200 cells/μL. CrAg prevalence was higher among inpatients (9.8% [95% CI, 4.0%-15.5%]) compared with outpatients (6.3% [95% CI, 5.3%-7.4%]). Conclusions. Te fndings of this review support current recommendations to screen all PLHIV who have a CD4 count =100 cells/μL for CrAg and suggest that screening may be considered at CD4 cell count =200 cells/μL.