Evaluation of two 4th generation point-of-care assays for the detection of Human Immunodeficiency Virus infection

Abstract

BackgroundFourth generation assays detect simultaneously antibodies for HIV and the p24 antigen, identifying HIV infection earlier than previous generation tests. Previous studies have shown that the Alere Determine HIV-1/2 Combo has lower than anticipated performance in detecting antibodies for HIV and the p24 antigen. Furthermore, there are currently very few studies evaluating the performance of Standard Diagnostics BIOLINE HIV Ag/Ab Combo.ObjectiveTo evaluate the performance of the Alere Determine HIV-1/2 Combo and the Standard Diagnostics BIOLINE HIV Ag/Ab Combo in a panel of frozen serum samples.Study designThe testing panel included 133 previously frozen serum specimens from the UCLA Clinical Microbiology & Immunoserology laboratory. Reference testing included testing for HIV antibodies by a 3rd generation enzyme immunoassay followed by HIV RNA detection. Antibody negative and RNA positive sera were also tested by a laboratory 4th generation HIV Ab/Ag enzyme immunoassay.ResultsReference testing yielded 97 positives for HIV infection and 36 negative samples. Sensitivity of the Alere test was 95% (88–98%), while the SD Bioline sensitivity was 91% (83–96%). Both assays showed 100% (90–100%) specificity. No indeterminate or invalid results were recorded. Among 13 samples with acute infection (HIV RNA positive, HIV antibody negative), 12 were found positive by the first assay and 8 by the second. The antigen component of the Alere assay detected 10 acute samples, while the SD Bioline assay detected only one.ConclusionsBoth rapid assays showed very good overall performance in detecting HIV infection in frozen serum samples, but further improvements are required to improve the performance in acute infection.

Comparison of Detection Limits of Fourth- and Fifth-Generation Combination HIV Antigen-Antibody, p24 Antigen, and Viral Load Assays on Diverse HIV Isolates

“…In fact, the Alere product insert shows that the Alere (p24 Ag component) assay detected 19 of the 28 seroconversion panels earlier than an FDAlicensed anti-HIV-1/2 EIA (31). Another study of serum samples reported sensitivities of the Alere assay of 95% and the SD Bioline assay of 91%; the p24 Ag component of the Alere test detected 10 of 13 acute infection samples (RNA positive, antibody negative), while the SD Bioline assay detected only 1 (32). However, in our study, these assays did not detect samples from the panel at any dilution, indicating either that the Ag component of these assays is not sensitive enough to detect the concentrations tested or that there was inhibition in the assay particular to the preparation of these panels.…”

Comparative multi-assay evaluation of Determine™ HIV-1/2 Ag/Ab Combo rapid diagnostic tests in acute and chronic HIV infection

“…All specimens from acutely HIV-1-infected, treatmentnaïve, immunoblot-indeterminate/positive patients (Fiebig stages IV-VI) scored positive in both versions of the Determine™ HIV-1/2 Combo, confirming the high sensitivity of this type of RDT to detect HIV-1 infection in acute infection during or after seroconversion [29][30][31]. Of note, the novel RDT failed to detect HIV-1-specific antibodies Table 3 Detection of chronic HIV-1 infection by the old and new versions of the Alere RDT in plasma specimens from HIV-1-infected patients compared to quantitative PCR, 4G-EIA, and p24 Ag assay…”

“…These results indicate an increased sensitivity of the new version of the RDT for detecting early HIV-1 infection prior to seroconversion. Several studies that have recently investigated the performance of the new RDT to detect infection in p24CA-positive, immunoblot-negative serum samples showed lower reactivity rates (< 30%) [30,33], while other groups demonstrated higher reactivity rates of more than 85% in similar specimens [29,31,32].…”

“…The sensitivity of this modified RDT to detect HIV-1/2 antibodies was shown to be high with low rates of false positive results [29][30][31]. However, its reported sensitivity for the detection of HIV p24CA antigen, the critical determinant for identifying acute HIV-1 infection, varied considerably: some studies found relatively high rates of p24CA detection (> 85%) in samples from infected individuals prior to seroconversion [29,31,32]. In contrast, other studies reported considerably lower p24CA detection rates (< 30%) in similar patient cohorts [30,33].…”

“…Several studies indicated a poor sensitivity for the detection of HIV-1 p24CA for the early version of this RDT [22][23][24][25][26][27][28], and therefore, Alere developed and released a modified version of this test. The sensitivity of this modified RDT to detect HIV-1/2 antibodies was shown to be high with low rates of false positive results [29][30][31]. However, its reported sensitivity for the detection of HIV p24CA antigen, the critical determinant for identifying acute HIV-1 infection, varied considerably: some studies found relatively high rates of p24CA detection (> 85%) in samples from infected individuals prior to seroconversion [29,31,32].…”