Impact of routine cryptococcal antigen screening and targeted pre-emptive fluconazole therapy in antiretroviral naive HIV-infected adults with less than 100 CD4 cells/muL: A systematic review and meta-analysis

Cryptococcal antigen (CrAg) screening and targeted pre-emptive fluconazole in antiretroviral naive HIV-infected adults with less than 100 CD4 cells/muL seems promising to reduce the burden of cryptococcal meningitis (CM). We searched MEDLINE, EMBASE, and Web of Science and used random-effect meta-analysis to assess the prevalence of blood CrAg-positivity (31 studies; 35,644 participants) and asymptomatic CM in CrAg-positives, incidence of CM and all-cause mortality in screened participants. Pooled prevalence of blood CrAg-positivity was 6% (95%CI: 5 – 7) and asymptomatic CM in CrAg-positives was 33% (95%CI: 21 – 45). Incidence of CM without pre-emptive fluconazole was 21.4% (95%CI: 11.6 – 34.4) and 5.7% (95%CI: 3.0 – 9.7) with pre-emptive fluconazole initiated at 800 mg/day. In CrAg-positives, post-screening lumbar puncture prior to initiating pre-emptive fluconazole at 800 mg/day further reduced incidence of CM to null and showed some survival benefits. However, all-cause mortality remained significantly higher in CrAg-positives than CrAg-negatives: RR: 2.2 (95%CI: 1.7 – 2.9, p<0.001)

• Population(s)
  • General HIV+ population
• Co-infections
  • Other