An Analysis of Predictive Sample-to-Cutoff Index for HIV Infection Confirmation Using Elecsys® HIV Combi PT Assay

Abstract

Background. Early and rapid diagnosis is crucial in HIV preventing and treatment. However, the false-positive rate (FPR) by 4-th generation detection assays was high in low-HIV-prevalence regions. Objectives. To analyze the relation between sample-to-cutoff index (COI) and HIV confirmatory results, and to explore a new COI threshold in our own laboratory to predict HIV infection. Methods. We retrospectively analyzed primarily reactive results by Elecsys® HIV combi PT assays and their confirmatory results by western blot (WB) at Nanjing Center for Disease Control and Prevention (CDC). The mean COI values of true positive (TP), false positive (FP), and indeterminate groups were compared, and receiver operating characteristic curve (ROC) analysis was performed to determine the optimal COI value for predicting HIV infection. Results. Totally 150,980 HIV serological results were reviewed, and 305 (0.2%) were primarily reactive. There are 82 (26.89%) true positives, 210 (71.92%) false positives, and 11 indeterminate samples confirmed by WB tests, and another 2 patients rejected WB tests. Mean COI values of TP (643.5) were greatly higher than that of FP (3.174) ( P < 0.0001 ), but there is no significant difference between FP and indeterminate groups. Combining the requirement of HIV diagnosis and ROC analysis, 9.87 was established as the optimal threshold to predict the infection, with 100% sensitivity and 99.99% specificity. Conclusions. By adjusting the COI threshold, the FP samples can be reduced and the efficiency of screening assays can be increased, which can save much additional reagent and staff costs and much time for delivery of HIV test results.

A case of a false positive HIV antigen/antibody screen in a pregnant woman at delivery and the clinical importance of reviewing signal-to-cutoff ratio values

“…All studies include a PPV for the screening test as well as a suggested S/Co ratio for optimal screening test performance. Study N = PPV Mean S/Co ratio of True Positives (Range) Mean S/Co ratio of False Positives (Range) Optimal S/Co ratio (100 % sensitivity maintained unless otherwise stated) Significance of difference in S/Co ratios Xia et al [25] 150,980 28 % 643.5 (9.95 - ≈ 1200) 3.174 (1–23.77) 9.87 (ROC) P < 0.0001 Wang et al [20] 84,702 44 % 458.15 (30.32–1171.33) 3.11 (1–18.55) 24.44 (ROC) P < 0.0001 Kim et al [10] 155,339 31.2 % overall (2.5 % for female samples) 385.97 (7.28–739.98) 2.94 (1.00–34.59) 8.8 (sensitivity 99.36 %) 6.6 (sensitivity 100 %) …”

“…From the other side, Alonso et al stated that 85 % of true positive samples in its study had S/Co above 100 [3] . Xia and colleagues showed that through raising the S/Co ratio threshold to 9.87, the test had the ability to maintain a sensitivity of 100 %, while eliminating 93 % of false positive results [25] . In the pregnancy population realm, a study reported that 100 % of low risk pregnant patients (n = 12) who had reactive ARCHITECT screening tests we ultimately found to be negative for HIV [4] .…”

Evaluation of a two-test strategy for HIV screening in a low-prevalence setting and the indications for optimizing clinical management

“…This will therefore lead to a risk of delayed medical treatment and increase stress for patients with false-positive results while waiting for the confirmatory results and the patients’ follow-up may fail. Recent studies have demonstrated that false-positive results can be excluded by increasing the signal-to-cutoff (S/CO) positive threshold [ 7 , 10 , 11 ]. In addition to this, rapid diagnostic test(RDT) has become a routine and a part of the standard of care in some HIV testing sites, and it can greatly reduce turnaround time and facilitate rapid linkage to care [ 2 , 12 ].…”