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

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.