Cryptococcal Antigen Screening in Patients Initiating ART in South Africa: A Prospective Cohort Study

Clin Infect Dis. 2016 Mar 1;62(5):581-587. doi: 10.1093/cid/civ936. Epub 2015 Nov 12.

Abstract

Background: Retrospective data suggest that cryptococcal antigen (CrAg) screening in patients with late-stage human immunodeficiency virus (HIV) initiating antiretroviral therapy (ART) may reduce cryptococcal disease and deaths. Prospective data are limited.

Methods: CrAg was measured using lateral flow assays (LFA) and latex agglutination (LA) tests in 645 HIV-positive, ART-naive patients with CD4 counts ≤100 cells/µL in Cape Town, South Africa. CrAg-positive patients were offered lumbar puncture (LP) and treated with antifungals. Patients were started on ART between 2 and 4 weeks and followed up for 1 year.

Results: A total of 4.3% (28/645) of patients were CrAg positive in serum and plasma with LFA. These included 16 also positive by urine LFA (2.5% of total screened) and 7 by serum LA (1.1% of total). In 4 of 10 LFA-positive cases agreeing to LP, the cerebrospinal fluid (CSF) CrAg LFA was positive. A positive CSF CrAg was associated with higher screening plasma/serum LFA titers.Among the 28 CrAg-positive patients, mortality was 14.3% at 10 weeks and 25% at 12 months. Only 1 CrAg-positive patient, who defaulted from care, died from cryptococcal meningitis (CM). Mortality in CrAg-negative patients was 11.5% at 1 year. Only 2 possible CM cases were identified in CrAg-negative patients.

Conclusions: CrAg screening of individuals initiating ART and preemptive fluconazole treatment of CrAg-positive patients resulted in markedly fewer cases of CM compared with historic unscreened cohorts. Studies are needed to refine management of CrAg-positive patients who have high mortality that does not appear to be wholly attributable to cryptococcal disease.

Keywords: HIV; antiretroviral therapy; cryptococcal antigen; cryptococcal meningitis; screening.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS-Related Opportunistic Infections / diagnosis*
  • AIDS-Related Opportunistic Infections / mortality
  • AIDS-Related Opportunistic Infections / prevention & control
  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Antifungal Agents / therapeutic use*
  • Antigens, Fungal / analysis*
  • Antigens, Fungal / blood
  • Antigens, Fungal / urine
  • Cohort Studies
  • Female
  • HIV Infections / drug therapy*
  • Humans
  • Male
  • Mass Screening
  • Meningitis, Cryptococcal / complications
  • Meningitis, Cryptococcal / diagnosis*
  • Meningitis, Cryptococcal / prevention & control
  • Prospective Studies
  • Treatment Outcome

Substances

  • Anti-HIV Agents
  • Antifungal Agents
  • Antigens, Fungal