Cryptococcal Antigenemia in HIV therapy-experienced Ugandans with Virologic Failure

BACKGROUND: Detectable serum or plasma cryptococcal antigen (CrAg) precedes symptomatic cryptococcal meningitis. The World Health Organization (WHO) recommends CrAg screening for HIV infected people with CD4<100 cells/mcL initiating antiretroviral therapy (ART). However, an increasing proportion of cryptococcosis patients 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 (≥1,000 copies/mL) using leftover plasma after viral load testing during September 2017-January 2018. For those CrAg-positive, we obtained ART history, meningitis occurrence, and 6-month survival via medical record review. RESULTS: Among 1,186 subjects with virologic failure, 35 (3.0%) were CrAg-positive with median ART duration of 41 months (IQR, 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 two 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% (735/1,151) of CrAg-negative (Odds Ratio = 6.0; 95% CI: 1.8-19.8, P = 0.001). CrAg prevalence was 4.2% (32/768) among those with viral loads ≥5000 copies/mL and 0.7% (3/419) among <5000 copies/mL. CONCLUSION: In addition to the CD4 threshold of <100 cells/mcL, reflexive CrAg screening should be considered in persons failing ART in Uganda with viral loads ≥5000 copies/mL.