Diagnostic accuracy of the Biosynex CryptoPS cryptococcal antigen semi-quantitative lateral flow assay in patients with advanced HIV disease.

Background: High cryptococcal antigen (CrAg) titers in blood are associated with subclinical meningitis and mortality in CrAg-positive individuals with advanced HIV-disease (AHD). We evaluated a novel semi-quantitative lateral flow assay (LFA), CryptoPS, that may be able to identify individuals with high CrAg titers in a cohort of AHD patients undergoing CrAg screening.Methods: In a prospective cohort of patients with AHD (CD4 ≤200 cells/μL) receiving CD4 count testing, CryptoPS and IMMY LFA CrAg testing were performed on whole blood by two operators blinded to results of the other assay. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CryptoPS were assessed against IMMY LFA as a reference. CryptoPS low-titer (T1 band) and high-titer (T2 band) results were compared against IMMY LFA titers obtained through serial dilution.Results: 916 specimens were tested. Sensitivity of the CryptoPS assay was 61.0% (25/41, 95% confidence interval [95%CI]: 44.5-75.8), specificity 96.6% (845/875, 95%CI: 95.1-97.7), PPV 45.5% (95%CI: 32.0-59.4), and NPV 98.1% (95%CI: 97.0-98.9). All (16/16) CryptoPS false-negatives were samples with IMMY titers ≤1:160. Of 29 patients (30 specimens) who tested positive on CryptoPS but negative on IMMY LFA, none developed cryptococcal meningitis over 3-months follow-up without fluconazole. Median CrAg titers were 1:20 (interquartile range [IQR] 0-1:160) in CryptoPS T1-positive samples and 1:2560 (IQR 1:1280-1:10240) in T2-positives.Conclusions: Diagnostic accuracy of the CryptoPS assay was sub-optimal in the context of CrAg screening, with poor sensitivity at low CrAg titers. However, the CryptoPS assay reliably detected individuals with high titers associated with poor outcomes.