Effectiveness of a National Reflex Laboratory Cryptococcal Antigen Screening Program for People With Advanced HIV Disease in South Africa: A Nationwide-Sampled Cohort Study (CAST-NET).

BACKGROUND

Cryptococcal antigen (CrAg) screening and pre-emptive treatment of antigenemia can reduce mortality among people living with HIV.

SETTING

We evaluated the effectiveness of a national CrAg screening program in South Africa.

METHODS

We enrolled a retrospective cohort of adults aged ≥18 years with a CD4 count <100 cells/µL and new antigenemia diagnosis at 442 facilities in a stratified-random sample of 27 subdistricts, 2017-2019. We determined a composite outcome of incident cryptococcal meningitis or death through 6 months.

RESULTS

Overall, 99% (85,791/86,274) of eligible patients had CrAg testing in the study subdistricts; 5124 (6.0%) tested CrAg positive. Among 1651 with imaged medical records and without concurrent meningitis, 76% (1261/1651) were outpatients. CrAg results were documented in records for 75% (1245/1651). Only 39% (649/1651) had a meningitis symptom review documented at a median of 14 days (IQR, 5-44) from their CrAg blood draw. Fluconazole was dispensed for 50% (827/1651) but only 32% (523/1651) had an adequate daily dose of ≥800 mg dispensed. The proportion with meningitis or death within 6 months was 23% (382/1651; 95% CI: 19% to 27%). Hospitalized patients had a 2.29 higher adjusted odds of meningitis/death within 6 months vs. outpatients (95% CI: 1.72 to 3.04; P < 0.001).

CONCLUSIONS

Nationwide reflex laboratory CrAg screening was successfully implemented. However, challenges existed for health care providers to act on positive CrAg results to exclude meningitis and dispense pre-emptive antifungal therapy. Our findings emphasize the critical need for improved linkage from reflex CrAg screening to clinical care, in both ambulatory and in-patient settings, to maintain the effectiveness of this intervention.