A Prospective Evaluation of a Multisite Cryptococcal Screening and Treatment Program in HIV Clinics in Uganda

Cryptococcus is a leading cause of AIDS-related mortality. Cryptococcal antigen (CrAg) is detectable in blood before meningitis onset and predicts death. CrAg screening among those with advanced HIV, and treatment of those CrAg+ with fluconazole, has demonstrated survival benefit. However, implementation and widespread uptake have been slow outside clinical trials.

We designed a CrAg screening program for routine care that incorporated intensive education and training of clinic staff. We evaluated programmatic implementation, including time to initiation of fluconazole, time to initiation of antiretroviral therapy, and 6-month clinical outcomes.

Between December 2015 and January 2017, 1440 persons were screened at 11 HIV clinics in Kampala, and CRAG+ prevalence was 6.5% (n = 94/1440) among adults with a CD4 <100 cells/µL. Of those CrAg+, 7 of 94 persons (7%) died or were lost before further clinic evaluation. Fifty-three persons (56%) were asymptomatic and had 6-month survival of 87% (46/53). Of CrAg+ persons, 28% (26/94) were symptomatic at the time of clinic return. Most had confirmed cryptococcal meningitis, and 54% (14/26) of the symptomatic CrAg+ persons were dead or lost at 6 months. Of the 7 symptomatic persons who declined lumbar puncture for further evaluation, all were dead or lost by 6 months.

All asymptomatic CrAg+ persons identified by our screening program who returned to clinic, initated fluconazole and antiretroviral therapy in a timely manner. Despite this, 27% of CrAg+ (asymptomatic and symptomatic) identified on routine screening were dead or lost to follow-up at 6 months, even with preemptive therapy for those asymptomatic, and standard amphotericin-based treatment for meningitis.