Sample-to-cutoff ratios using Architect HIV Ag/Ab Combo: The influence with the results of supplemental tests and optimal cutoff value to predict HIV infection.

BACKGROUND: The Architect HIV Ag/Ab Combo has excellent performance for HIV screening; however, the false-positive rate (FPR) was high in low HIV prevalence setting. OBJECTIVES: The purpose of this study was to analyze the influence of sample-to-cutoff (s/co) ratios by Architect HIV Ag/Ab Combo with the results of confirmatory test and explore the potential utility of s/co to predict HIV infection. METHODS: A retrospective review on Architect HIV Ag/Ab Combo reactive results was performed at a teaching hospital in Xi'an. The s/co values in different groups, that is, true positives (TP) and false positives (FP), different Western blotting (WB) bands among WB-positive cases, were compared. The receiver operating characteristic curve (ROC) analysis was used to determine the optimal cutoff value for predicting HIV infection. RESULTS: During the study period, 219 out of 84 702 patients were reactive by ARCHITECT with a 0.0992% of HIV prevalence and a 56.25% of FPR. The mean s/co ratios in TP were significantly higher than that in FP (458.15 vs 3.11, P < 0.0001). Among the WB-positive cases, the s/co ratios increased significantly with the increase in the number of bands, P = 0.0065. The optimal cutoff (24.44) by ROC analysis can provide the highest sum of sensitivity (100%) and specificity (100%) with no FP results. CONCLUSIONS: For Architect HIV Ag/Ab Combo, the FPR is reduced when s/co ratios increase, and the s/co ≥24.44 may be reliable to predict HIV infection.

Evaluation of the Architect HIV Ag/Ab Combo Assay in a low-prevalence setting: The role of samples with a low S/CO ratio.

BACKGROUND: The Architect HIV Ag/Ab Combo Assay, a fourth-generation ELISA, has proven to be highly reliable for the diagnosis of HIV infection. However, its high sensitivity may lead to false-positive results. OBJECTIVES: To evaluate the diagnostic performance of Architect in a low-prevalence population and to assess the role of the sample-to-cutoff ratio (S/CO) in reducing the frequency of false-positive results. STUDY DESIGN: We conducted a retrospective study of samples analyzed by Architect between January 2015 and June 2017. Positive samples were confirmed by immunoblot (RIBA) or nucleic acid amplification tests (NAATs). Different S/CO thresholds (1, 2.5, 10, 25, and 100) were analyzed to determine sensitivity, specificity, and negative and positive predictive values (NPV, PPV). ROC analysis was used to determine the optimal S/CO. RESULTS: A total of 69,471 samples were analyzed. 709 (1.02%) were positive by Architect. Of these, 63 (8.89%) were false-positive results. Most of them (93.65%) were in samples with S/CO < 100. However, most confirmations by NAATs (12 out of 19 cases) were also recorded for these samples. The optimal S/CO was 2.5, which provided the highest area under the ROC curve (0.9998) and no false-negative results. With this S/CO, sensitivity and specificity were 100.0%, and PPV and NPV were 95.8% and 100.0%, respectively. In addition, the frequency of false-positive results decreased significantly to 4.15%. CONCLUSIONS: Although Architect generates a relatively high number of false-positive results, raising the S/CO limit too much to increase specificity can lead to false-negative results, especially in newly infected individuals.

Performance of an alternative HIV diagnostic algorithm using the ARCHITECT HIV Ag/Ab Combo assay and potential utility of sample-to-cutoff ratio to discriminate primary from established infection.

BACKGROUND: The ARCHITECT HIV Ag/Ab Combo assay has a wide dynamic range for determining the sample-to-cutoff ratio (S/CO) values compared to other diagnostic HIV antibody assays. OBJECTIVES: Determine the performance of an HIV testing algorithm that uses the ARCHITECT combo assay in the clinical setting and explore the utility of the signal-to-cutoff (S/CO) ratio to predict acute HIV-1 infection status. STUDY DESIGN: A retrospective analysis of clinical samples from a hospital and referral population screened for HIV-1 infection between May 2011 and March 2013. Repeatedly reactive samples were tested using the Multispot HIV-1/HIV-2 rapid test and depending on that result, confirmatory orthogonal testing used the Western blot (WB) for HIV-1, Immunoblot for HIV-2 and nucleic acid amplification testing (NAAT) for HIV RNA. RESULTS: A total of 21,317 test results were evaluated of which 509 were ARCHITECT repeatedly reactive; of these, 422 were Multispot-reactive only for HIV-1 (413 WB-positive; 9 indeterminate), 4 were Multispot-reactive for both HIV-1 and HIV-2 (one HIV-2 immunoblot-positive with 17 HIV-2 RNA copies/mL) and 83 were Multispot-non-reactive of which 15 were HIV-1 RNA positive and represented acute HIV-1 infection. There was an association among the ARCHITECT S/CO (median; IQR) values for antibody-negative (0.14; 0.11-0.16), acute infection (33; 2.1-76) and established HIV-1 infection (794; 494-1,029) (Kruskal-Wallis, p<0.0001). CONCLUSIONS: The ARCHITECT combo assay with Multispot confirmation and reserved use of HIV-1 WB, HIV-2 Immunoblot and HIV NAAT for Multispot dual HIV-1/2 infection, and NAAT alone for Multispot-negative specimens, had a suitable test performance for detecting acute and established HIV infection.