With a prevalence of detectable sub-clinical cryptococcal infection averaging 7.2 % (95 % CI 6.8-7.6 %) among 36 cohorts with CD4 <100 cells/μL in Africa, together with data showing that preemptive fluconazole prevents overt cryptococcal disease in this population, implementing a screen and treat strategy as part of HIV care practice among patients with CD4 <100 cells/μL could prevent the incidence of often fatal cryptococcal meningitis in the setting of the HIV pandemic. This evidence concerns the gene CD4 and Cryptococcal meningitis.