Project Overview
Project title: The CAST- NET study is a multi-year observational programmatic study that sought to evaluate the effectiveness of South Africa’s national cryptococcal antigen (CRAG) screening and pre-emptive treatment programme, in order to improve HIV care and survival of persons living with advanced HIV disease.
Cryptococcal antigen (CrAg) screening and pre-emptive treatment of antigenaemia can reduce mortality among people living with HIV.

Key Objectives
Part 1 of Study
In CAST-NET Part 1, we conducted a retrospective cohort study of adults living with advanced HIV who screened positive for cryptococcal antigenaemia in 2017-2019 in 27 sub-districts, and used retrospective record review and several other routine data sources to document the clinical care of participants and their 6-month outcomes. The Division partnered with Epicentre Health Research to collect data at facilities. A team of medical officers in the Division completed data abstraction for just over 2000 patient records and 1651 participants were included in the final analysis.
Part 2 of Study
Part 2 of the CAST-NET study, implemented for 6 months during 2021 consisted of a pragmatic cluster-randomized trial, with the aim of assessing whether a health systems intervention at healthcare facility level (mediated through informal appointment of a ”Crypto Champion” at each facility could improve follow-up and initiation of pre-emptive fluconazole therapy among newly-diagnosed persons with antigenaemia. We also compared 6-month cryptococcal meningitis-free survival among people with antigenaemia at intervention versus control facilities. This part of the project was pared back owing to COVID-19 pandemic restrictions.
Project Map Key
Persons with positive reflex CrAg tests during study period and in study sub-districts assessed for eligibility.
Excluded based on chart finding (total n = 2029)
- No records located (n = 1323)
- Insufficient information in records, e.g. blank with no handwritten notes (n=706)
Potentially-eligible persons with records located and data abstracted into study database
Did not meet eligibility based on records (total n = 1079)
- HIV-seronegative, n=1
- Not study sub-district, n=259
- Prior cryptococcosis, n=742
- Specimen date before 31 January 2017, n=12
- No records located after CrAg screen date, n=65
Eligible persons after record review
Excluded based on clinical history (total n = 365)
- No return visit after CrAg screen, n=197
- Concurrent cryptococcal meningitis, n=168
Final reflex screening cohort included in analysis
Ambulatory
n = 1261
Hospitalised
n = 390


