Reduction of the diagnostic window with a new combined p24 antigen and human immunodeficiency virus antibody screening assay

Gürtler, Lutz; Mühlbacher, Annelies; Michl, Ulrike; Hofmann, H; Paggi, Giancarlo; Bossi, V.; Thorstensson, Rigmor; Villaescusa, Roberto; Eiras, A.; Hernandez, J. E.; Melchior, Walter; Donié, F; Weber, Bernard

doi:10.1016/s0166-0934(98)00094-9

Cited by 108 publications

(85 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…HIV RT has been included in analogy to EnzymunTest HIV Combi in the antigenic mixture of Cobas Core HIV Combi EIA in order to avoid false-negative results in the early seroconversion phase after disappearance of HIV antigenemia since p24 Ag would have interfered with anti-p24 for HIV Ag capture. As shown by the results of our study, in only 3 of 94 seroconversions were transient borderline-negative results measured with Cobas Core HIV Combi EIA in the early phase of seroconversion; this effect was also observed with EnzymunTest HIV Combi in a former study (12) and could therefore possibly result from the absence of anti-p24 detection. The second reason for including RT as the Ag in the Cobas Core HIV Combi EIA is that, with gp41 alone, the sensitivity of the assay would have been impaired not only during seroconversion but also at all stages of the disease.…”

Section: Discussionsupporting

confidence: 69%

“…Although a limited number of lysates were tested, Cobas Core HIV Combi EIA was likely to have a higher sensitivity for HIV-2 Ag detection than the Coulter HIV p24 Ag assay. Previous studies reported a variable sensitivity of fourth-generation assays for HIV-1 group M non-B subtypes and HIV-2 (12,20,33).…”

Section: Discussionmentioning

confidence: 99%

“…The risk of interference is potentially higher with the HIV combined assays than with single-Ag or -antibody EIAs, since both serological markers are determined in one test batch. The specificity for blood donor screening (99.6 to 99.8%) is lower than that of thirdgeneration HIV EIAs (12,19). The higher rate of false-positive results (0.2%) of HIV combined assays has a particularly negative effect in cases of high sample throughput and low prevalence as in blood donor screening mainly because a separate Ag detection must be carried out in addition to the antibody confirmatory assay (Western blotting) in order to rule out an HIV infection (12).…”

mentioning

confidence: 85%

“…Fourth-generation HIV screening assays that make combined HIV Ag and antibody detection possible in one test batch have been licensed in Europe since 1997 (12,19,20,23,26,(30)(31)(32)(33)(34)(35). These combined assays offer the advantage of early detection of HIV infection via p24 Ag detection at a technical burden and financial cost more or less equal to those for HIV antibody testing using third-generation EIAs.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Multicenter Evaluation of a New Automated Fourth-Generation Human Immunodeficiency Virus Screening Assay with a Sensitive Antigen Detection Module and High Specificity

et al. 2002

Self Cite

View full text Add to dashboard Cite

Fourth-generation assays for the simultaneous detection of human immunodeficiency virus (HIV) antigenSince the first enzyme immunoassays (EIA) for blood donor screening and laboratory diagnosis of human immunodeficiency virus (HIV) infection were licensed over 15 years ago, the quality of these tests has been continuously improved by the use of recombinant antigens and synthetic peptides (second test generation) and the sandwich EIA technology (third test generation) (10, 36). There is however a residual risk for false-negative results. The potential causes include the diagnostic window in the preseroconversion phase, genetic variability, atypical seroconversions, a delayed or absent immune re-

show abstract

Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 85%

mentioning

confidence: 99%

See 2 more Smart Citations

Multicenter Evaluation of a New Automated Fourth-Generation Human Immunodeficiency Virus Screening Assay with a Sensitive Antigen Detection Module and High Specificity

et al. 2002

Self Cite

View full text Add to dashboard Cite

show abstract

“…Fourth generation laboratory-based HIV assays have the ability to detect antibodies to HIV-1/2 and p24 antigen simultaneously, which reduces the window period to an average of 2 weeks (most rapid HIV assays only detect HIV antibodies, with an average window period of 3 to 4 weeks) (Gurtler et al, 1998;Stekler et al, 2007). Alere (Waltham, USA) has recently launched the Determine TM HIV-1/2 Ag/Ab Combo, which is the first rapid fourth generation HIV assay (Alere, 2010a).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the Determine™ fourth generation HIV rapid assay

Brauer

Villiers

Mayaphi

2013

Journal of Virological Methods

View full text Add to dashboard Cite

Assays that detect p24 antigen reduce the diagnostic window period of HIV testing. Most point-of-care HIV assays have poor sensitivity to diagnose acute HIV infection as they only detect antibodies against HIV-1 and HIV-2 (HIV-1/2). This was a cross-sectional laboratorybased study that evaluated the performance of the Determine TM HIV-1/2 Ag/Ab Combo fourth generation rapid strip -currently the only rapid assay that detects both HIV-1/2 antibodies and p24 antigen. A total of 79 serum specimens (29 positive for HIV antibodies only, 14 positive for HIV antibodies and p24 antigen, 20 HIV-negative, and 16 positive for p24 antigen only) were used for the evaluation. Results were compared with those from validated fourth generation HIV ELISAs. The Determine TM Combo rapid strips had a sensitivity of 90.7% and a specificity of 100% for the detection of HIV-1/2 antibodies. Its sensitivity for the detection of p24 antigen was only 10% (3 out of 30 p24 antigen positive specimens). This implies that most acute HIV infections will be missed with this assay. The need for a point-of-care assay which can detect acute HIV infection reliably still remains, particularly for use in a high prevalence setting such as South Africa.

show abstract

Optimized virus disruption improves detection of HIV-1 p24 in particles and uncovers a p24 reactivity in patients with undetectable HIV-1 RNA under long-term HAART

et al. 2006

View full text Add to dashboard Cite

HIV-1 p24 antigen (p24) measurement by signal amplification-boosted ELISA of heat-denatured plasma is being evaluated as an alternative to HIV-1 RNA quantitation in resource-poor settings. Some observations suggested that virion-associated p24 is suboptimally detected using Triton X-100-based virus dissociation buffer (kit buffer). A new reagent (SNCR buffer) containing both denaturing and non-denaturing detergents was therefore developed and evaluated. The SNCR buffer increased the measured p24 concentration about 1.5- to 3-fold in HIV-negative plasma reconstituted with purified HIV-1 particles, while not increasing the background. Among 127 samples of HIV-1-positive patients with moderate to high concentrations of HIV-1 RNA the increase was about threefold across the entire concentration range (P < 0.0001). Specificity before neutralization among prospectively tested clinical samples ruled HIV-negative was 828 of 845 (98.0%) for the SNCR buffer and 464 of 479 (96.9%) for kit buffer. Specificity after confirmatory neutralization of reactive samples or a follow-up test was 100% with either buffer. Surprisingly, the SNCR buffer revealed a p24 reactivity in 115 of 187 samples (61.5%) from adult patients exhibiting undetectable HIV-1 RNA below 5 copies/ml for a duration of 6-30 months under HAART (3.7% with kit buffer). The rate of p24 reactivity in these patients did not decrease with duration of HAART. In conclusion, the SNCR buffer improves the detection of particle-associated HIV-1 p24, thereby increasing the measured p24 concentration in samples with medium to high HIV-1 RNA. It also uncovers the presence of a p24 reactivity, whose identity remains to be determined, in a significant fraction of samples with undetectable HIV-1 RNA under long-term HAART.

show abstract

Reduction of the diagnostic window with a new combined p24 antigen and human immunodeficiency virus antibody screening assay

Cited by 108 publications

References 15 publications

Multicenter Evaluation of a New Automated Fourth-Generation Human Immunodeficiency Virus Screening Assay with a Sensitive Antigen Detection Module and High Specificity

Multicenter Evaluation of a New Automated Fourth-Generation Human Immunodeficiency Virus Screening Assay with a Sensitive Antigen Detection Module and High Specificity

Evaluation of the Determine™ fourth generation HIV rapid assay

Optimized virus disruption improves detection of HIV-1 p24 in particles and uncovers a p24 reactivity in patients with undetectable HIV-1 RNA under long-term HAART

Contact Info

Product

Resources

About