Impact of Routine Cryptococcal Antigen Screening and Targeted Preemptive Fluconazole Therapy in Antiretroviral-naive Human Immunodeficiency Virus-infected Adults With CD4 Cell Counts <100/μL: A Systematic Review and Meta-analysis

Clin Infect Dis. 2019 Feb 1;68(4):688-698. doi: 10.1093/cid/ciy567.

Abstract

Cryptococcal antigen (CrAg) screening and targeted preemptive fluconazole in antiretroviral-naive human immunodeficiency virus-infected adults with CD4 cell counts <100/μL seems promising as a strategy 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; 35644 participants) and asymptomatic CM in CrAg-positive participants and the incidence of CM and the all-cause mortality rate in screened participants. The pooled prevalence of blood CrAg-positivity was 6% (95% confidence interval [CI], 5%-7%), and the prevalence of asymptomatic CM in CrAg-positive participants was 33% (95% CI, 21%-45%). The incidence of CM was 21.4% (95% CI, 11.6%-34.4%) without preemptive fluconazole and 5.7% (95% CI, 3.0%-9.7%) with preemptive fluconazole therapy initiated at 800 mg/d. In CrAg-positive participants, postscreening lumbar puncture before initiating preemptive fluconazole at 800 mg/d further reduced the incidence of CM to null and showed some survival benefits. However, the all-cause mortality rate remained significantly higher in CrAg-positive than in CrAg-negative participants (risk ratio, 2.2; 95% CI, 1.7-2.9; P < .001).

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antifungal Agents / administration & dosage*
  • CD4 Lymphocyte Count
  • Chemoprevention / methods*
  • Female
  • Fluconazole / administration & dosage*
  • HIV Infections / complications*
  • HIV Infections / pathology
  • Humans
  • Incidence
  • Male
  • Meningitis, Cryptococcal / epidemiology
  • Meningitis, Cryptococcal / prevention & control*
  • Middle Aged
  • Prevalence
  • Young Adult

Substances

  • Antifungal Agents
  • Fluconazole