Cryptococcal antigenemia in human immunodeficiency virus antiretroviral therapy-experienced ugandans with virologic failure

Edward Mpoza, Radha Rajasingham, Lillian Tugume, Joshua Rhein, Maria Sarah Nabaggala, Isaac Ssewanyana, Wilson Nyegenye, Grace Esther Kushemererwa, Vivienne Mulema, Julius Kalamya, Charles Kiyaga, Joseph Kabanda, Mina Ssali, David R. Boulware, David B. Meya

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


BACKGROUND: Detectable serum or plasma cryptococcal antigen (CrAg) precedes symptomatic cryptococcal meningitis. The World Health Organization recommends CrAg screening for human immunodeficiency virus-positive persons with CD4 count <100 cells/μL initiating antiretroviral therapy (ART). However, an increasing proportion of patients with cryptococcosis are now ART experienced. Whether CrAg screening is cost-effective in those with virologic failure is unknown.

METHODS: We retrospectively performed nationwide plasma CrAg testing among ART-experienced Ugandan adults with virologic failure (≥1000 copies/mL) using leftover plasma after viral load testing during September 2017-January 2018. For those who were CrAg positive, we obtained ART history, meningitis occurrence, and 6-month survival via medical records review.

RESULTS: Among 1186 subjects with virologic failure, 35 (3.0%) were CrAg positive with median ART duration of 41 months (interquartile range, 10-84 months). Among 25 subjects with 6-month outcomes, 16 (64%) survived, 7 (28%) died, and 2 (8%) were lost. One survivor had suffered cryptococcal meningitis 2 years prior. Two others developed cryptococcal meningitis and survived. Five survivors were known to have received fluconazole. Thus, meningitis-free survival at 6 months was 61% (14/23). Overall, 91% (32/35) of CrAg-positive persons had viral load ≥5000 copies/mL compared with 64% (735/1151) of CrAg-negative persons (odds ratio, 6.0 [95% confidence interval, 1.8-19.8]; P = .001). CrAg prevalence was 4.2% (32/768) among those with viral loads ≥5000 copies/mL and 0.7% (3/419) among those with viral loads <5000 copies/mL.

CONCLUSIONS: In addition to the CD4 threshold of <100 cells/μL, reflexive CrAg screening should be considered in persons failing ART in Uganda with viral loads ≥5000 copies/mL.

Original languageEnglish (US)
Pages (from-to)1726-1731
Number of pages6
JournalClinical Infectious Diseases
Issue number7
StatePublished - Oct 1 2020

Bibliographical note

Publisher Copyright:
© The Author(s) 2019.


  • ART experienced
  • Cryptococcal antigenemia
  • HIV
  • Virologic failure


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