Seven Human Immunodeficiency Virus (HIV) Antigen-Antibody Combination Assays: Evaluation of HIV Seroconversion Sensitivity and Subtype Detection

Abstract

In this study, we evaluated the performance of two prototype human immunodeficiency virus (HIV) antigen-antibody (Ag-Ab) combination assays, one from Abbott Laboratories (AxSYM HIV Ag-Ab) and the other from bioMerieux (VIDAS HIV Duo Ultra), versus five combination assays commercially available in Europe. The assays were Enzygnost HIV Integral, Genscreen Plus HIV Ag-Ab, Murex HIV Ag-Ab Combination, VIDAS HIV Duo, and Vironostika HIV Uniform II Ag-Ab. All assays were evaluated for the ability to detect p24 antigen from HIV-1 groups M and O, antibody-positive plasma samples from HIV-1 groups M and O, HIV-2, and 19 HIV seroconversion panels. Results indicate that although all combination assays can detect antibodies to HIV-1, group M, subtypes A to G, circulating recombinant form (CRF) A/E, and HIV-1 group O, their sensitivity varied considerably when tested using diluted HIV-1 group O and HIV-2 antibody-positive samples. Among combination assays, the AxSYM, Murex, and VIDAS HIV Duo Ultra assays exhibited the best antigen sensitivity (at ∼25 pg of HIV Ag/ml) for detection of HIV-1 group M, subtypes A to G and CRF A/E, and HIV-1 group O isolates. However, the VIDAS HIV Duo Ultra assay had a lower sensitivity for HIV-1 group M and subtype C, and was unable to detect subtype C antigen even at 125 pg of HIV Ag/ml. The HIV antigen sensitivity of the VIDAS HIV Duo and Genscreen Plus combination assays was ∼125 pg of HIV Ag/ml for detection of all HIV-1 group M isolates except HIV-1 group O while the sensitivity of Vironostika HIV Uniform II Ag-Ab and Enzygnost HIV Integral Ag-Ab assays for all the group M subtypes was >125 pg of HIV Ag/ml. Among the combination assays, the AxSYM assay had the best performance for detection of early seroconversion samples, followed by the Murex and VIDAS HIV Duo Ultra assays

Detection of an Acute HIV-1 Infection Case in the Last Day of Diagnostic Window through a Combination of Two Fourth-Generation Screening Assays on a Brazilian Public Healthy Institution: We Close the Window

“…In other studies, no evidence was found for a second diagnostic window due to the impaired sensitivity of the antibody detection module of different 4th generation HIV assays [13,17]. These studies did not observe a significant drop in the measured index values or negative results in the transient period between the decline of antigenemia and the beginning of the seroconversion.…”

“…No seronegativity for different samples was observed, but the index values dropped near the cut off [13]. This was not observed for this case, instead, the levels of p24 antigen did not dropped in two days, but increased and then the antibodies appeared.…”

“…An HIV infection can potentially be detected with 4th generation HIV assays within the first 2weeks after exposure [10,13,14]. However, in addition to the first diagnostic window, a so-called second diagnostic window has been reported; this second diagnostic window may occur when 4 th generation HIV assays are used.…”

HIV-1 Diversity and Its Implications in Diagnosis, Transmission, Disease Progression, and Antiretroviral Therapy

“…These assays provide an advantage for detection of infection during the window period prior to seroconversion since the diagnostic window may be reduced by an average of 5 days relative to an IgM-sensitive EIA (Fiebig et al, 2003;Weber et al, 1998). However, some fourth-generation assays showed low sensitivity in the detection of p24 antigen from some non-subtype B HIV-1 strains (A, C, F, H, CRF01_AE, O) (Kwon et al, 2006;Ly et al, 2007;Ly et al, 2004;Ly et al, 2001;Weber, 2002). This low sensitivity in antigen detection may be attributed to differences in viral epitopes of the different HIV genetic forms which may not be recognized by the monoclonal antibody used in the assay (Plantier et al, 2009a).…”

“…Key epitope(s) targeted by these assays might be modified or eliminated by the occurrence of natural polymorphisms within the IDR region associated with the genetic variation of HIV-1, ultimately leading to reduced sensitivity or lack of antibody detection (Brennan et al, 2006;Gaudy et al, 2004). A few cases of false-negative results involving, for example, subtypes B, C, and F, and resulting from major mutations of the IDR epitope have been described (Aghokeng et al, 2009;Gaudy et al, 2004;Ly et al, 2007;Ly et al, 2004;Ly et al, 2001;Zouhair et al, 2006). Earlier analysis of specimens from patients infected with group O viruses revealed that some commercial immunoassays failed to detect group O infections (Eberle et al, 1997;Loussert-Ajaka et al, 1994;Schable et al, 1994;Simon et al, 1994).…”