Effects of Routine Cryptococcal Antigen Screening in ART-Naïve HIV+ Patients

Cryptococcus neoformans
Cryptococcus neoformans
Pre-emptive fluconazole treatment following screening to exclude cryptococcal meningitis may increase survival in CrAg-positive, asymptomatic patients with HIV.

In blood cryptococcal antigen (CrAg)-positive, asymptomatic patients with HIV starting antiretroviral agents with <100 CD4 cells/μL, preemptive fluconazole following post-screening lumbar puncture to exclude cryptococcal meningitis (CM) significantly reduces the rate of CM and has some survival benefits, according to study results published in Clinical Infectious Diseases.

The meta-analysis included 31 studies with 35,644 participants from MEDLINE, EMBASE, and Web of Science. The researchers used random-effect meta-analysis to assess the prevalence of blood CrAg-positivity and asymptomatic CM in CrAg-positive participants. They also assessed incidence of CM and all-cause mortality.

Overall, the prevalence of blood CrAg-positive was 6% and the prevalence of asymptomatic CM in CrAg-positive participants was 33%.

The researchers found that the incidence of CM without preemptive fluconazole was 21.4% compared with 5.7% with preemptive fluconazole initiated at 800 mg/d.

For CrAg-positive study participants, the results suggest that post-screening lumbar puncture prior to initiating preemptive fluconazole further reduced the incidence of CM to 0 and showed some survival benefits.

However, CrAg-positive participants still had significantly higher rates of all-cause mortality compared with CrAg-negative participants (relative risk, 2.2; CI, 1.7-2.9, P <.001).

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“The high prevalence of asymptomatic CM in CrAg-positive patients together with low uptake of lumbar puncture, justifies the development of reliable point-of-care tests capable at point of screening, of identifying CrAg-positive patients at higher risk of underlying asymptomatic CM,” the researchers wrote.


Temfack E, Bigna JJ, Luma HN, et al. Impact of routine cryptococcal antigen screening and targeted pre-emptive fluconazole therapy in antiretroviral naïve HIV-infected adults with less than 100 CD4cells/μL: a systematic review and meta-analysis [published online July 18, 2018]. Clin Infect Dis. doi:10.1093/cid/ciy567/5055339