Combi PT Assay Research Articles

A method to alleviate false-positive results of the Elecsys HIV combi PT assay

To explore the effects of urea dissociation on reducing false-positive results of the Elecsys HIV combi PT assay. A retrospective analysis was used to evaluate the false-positive rate of the Elecsys HIV combi PT assay. Six false-positive sera, six positive sera and six sera from patients with early HIV infection were collected. Dissociation was performed using 1 mol/L, 2 mol/L, 4 mol/L, 6 mol/L, or 8 mol/L urea, and HIV screening assay were then detected to select the appropriate concentration of urea dissociation. Next, 55 false-positive sera and 15 sera from early HIV infection were used to verify the best concentration of urea to achieve dissociation. Retrospective analysis showed that the COI of the Elecsys HIV combi PT assay in false-positive sera ranged from 1.0 to 200.0, and approximately 97.01%(227/234) of false-positive sera were in the range of 1.0–15.0. The avidity index (AI) in positive and false-positive sera decreased as the urea dissociation concentration increased. When the dissociation concentration was 6 mol/L, the AI of false-positive serum was between 0.0234 and 0.2567, and the AI of early HIV infection sera was between 0.4325 and 0.5017. The difference in AI between false-positive and positive samples was significant. When negativity was defined as an AI of less than 0.3970, the sensitivity and specificity were 100.0% and 100.0%, respectively. Urea-mediated dissociation could significantly reduce the false-positive rate of the Elecsys HIV combi PT assay with a low COI. Our findings provided a reference for distinguishing positive and false-positive of the Elecsys HIV combi PT assay.

The evaluation of low cut-off index values of Elecsys® HIV combi PT assay in predicting false-positive results.

ObjectiveTo analyze the results of different cut‐off index (COI) values of Elecsys® HIV combi PT assay and to assess the role of COI in reducing the frequency of false‐positive results.MethodsWe conducted a retrospective study of samples analyzed by Elecsys® HIV combi PT assay, a 4th‐generation ECLIA, between 2016 and 2017. A total amount of 379 122 samples were collected for HIV (Human Immunodeficiency Virus) screening.ResultsA total of 379 122 samples were analyzed. 2528 (0.67%) were positive by Elecsys® HIV combi PT. Of these, 468 were false‐positive results, and most of them (94.87%) were in samples with 1 < COI < 15. The false‐positive rate was 0.12%. Patients with false‐positive samples were more distributed in elder (P < .001) and female (P < .001) than true‐positive specimens. The median COI in true‐positive specimens was (385.20), which is significantly higher than false‐positive specimens (2.08). The consistency between Elecsys® HIV combi PT assay and 3rd‐generation and positive predictive value (PPV) increased with higher COI values. Cancer, infection, and neurological diseases were considered the potential confounding factors of HIV false‐positive results (19.44%, 11.11%, and 6.62%, respectively).ConclusionSamples with low COI values, especially those contain confounding factors, need to be further scrutinized to determine whether the confounding factors may cause false‐positive problem. In addition, the hypothesis that low COI values may predict false‐positive results is valid.

Performance evaluation of Elecsys HIV Duo on cobas e 801 using clinical samples in China.

The prevalence and incidence of human immunodeficiency viruses (HIV) infection are rapidly increasing, and novel HIV genotypes are emerging. This study evaluated the sensitivity and specificity of Elecsys HIV Duo assay in population with the epidemic of multiple genotypes of HIV‐1 infection. Specificity of the Elecsys HIV Duo assay was determined using 3039 serum samples from patients receiving routine HIV‐1 screening tests in China. Sensitivity was assessed with seroconversion panels. Additional 67 positive from newly diagnosed HIV‐1 infected samples were also included to test assay performance on various HIV‐1 genotypes. The assay performance was compared with that of the Elecsys HIV Combi PT assay. The genotypes of all HIV‐1 positive samples were determined with phylogenetic analyses on the 1.1 kb Pro‐RT region of pol gene for drug resistance tests. The Elecsys HIV Duo assay had a slightly higher specificity (99.93% vs 99.84%) and equivalent sensitivity to Elecsys HIV Combi PT assay. Seventy‐two HIV‐1 positive samples, including 12 antigens positive samples, were distinguished by Elecsys HIV Duo. Among them, 43 samples were circulating recombinant form (CRF)01_AE, followed by 13 of CRF07_BC, 10 of subtype B, 4 of URF_0107, 1 of URF_01B and 1 of CRF02_AG. The Elecsys HIV Duo assay showed good performance for the Chinese population with an epidemic of multiple HIV genotypes.

Clinical Application Evaluation of a Fourth-Generation HIV Antigen Antibody Combination Screening Assay.

Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) are infectious diseases with high mortality. Early diagnosis is crucial. Combining HIV antibody and p24 antigen, the Elecsys HIV combi PT assay is a fourth generation HIV screening assay. The sensitivity and specificity of this assay was examined. A total of 111,556 samples was conducted from January 1, 2016, to June 30, 2018 in Zhongshan Hospital of Yat-Sen University. We conducted a fourth-generation HIV test of retrospective HIV screening samples and assessed the reliability of using signal-to-cutoff (S/CO) ratios to distinguish false positive HIV antibody reactions and analyzed false positives. A total of 122 specimens were confirmed as HIV-1 infected by western blot (WB) and HIV nucleic acid assays. The median S/CO ratio for HIV false positive specimens was 3.27, while for the HIV-infected specimen it was 391.7. Receiver operating characteristic (ROC) analysis showed that the best diagnostic point for HIV was 22.85 S/CO. The sensitivity, specificity, and Youden index were 100%, 97.8%, and 0.978, respectively. The highest false positive rate of 26.4% was found in patients with malignant tumors and blood diseases. The results of this study show that the fourth-generation Elecsys HIV combination PT test can identify early HIV infected and can be a useful adjunct to help clinicians to manage the disease by viral load testing and starting an appropriate therapy. Our research data provides a reference for subsequent research and HIV testing in the region.

A retrospective analysis of the application of the Elecsys® HIV combi PT assay in southern China.

Fourth-generation HIV assays have been implemented worldwide as a screening test for many years. Understanding the performance of fourth-generation assay in low HIV prevalence region is pivotal to interpret the test result correctly. In this study, retrospective analysis was used to evaluate application of the Elecsys® HIV combi PT assay. A total of 85043 specimens from a low prevalence setting were detected between June 2013 and October 2015. We evaluated the false-positive rate (FPR), specificity, and positive predictive value (PPV). The specificity between male and female were 99.85% and 99.82%, respectively. The PPV on male (50.75%) was higher than female (17.05%) significantly, while the FPR was 0.15% and 0.18%. The gap between false-positive (median: 1.83, [IQR]: 1.30, 3.38) and confirmed-positive (median: 407.5, [IQR]: 184.2, 871.7) is enormous. The highest s/co ratio for false-positive cases was 85.45, while the lowest s/co ratio for confirmed-positive cases was 59.68. Various reasons were attributed to false-positive cases. Optimal cutoff value is needed to be set to reduce the false-positive cases and predict the final status of HIV infection reliably. Retrospective analysis will help us to understand more about diagnosis of HIV.

Using Elecsys® HIV Combi PT assay to identify acute and early HIV infection in a teaching hospital of southwest China.

This study is the first attempt to evaluate the use of the Elecsys® HIV combi PT assay in identifying acute and early HIV infection in southwest China. We also analyzed the extent of cutoff ratios overlap between false-positive and true-positive results to aid the identification of HIV infection, using samples from the West China Hospital in Chengdu, Sichuan Province from April 2012 to December 2013. Reactive results from a screening test were retested and all repeatedly reactive samples - if available - were confirmed with Western blot, HIV-1 p24 antigen, or HIV-1 RNA. Of 241,840 samples screened, the Elecsys® HIV combi PT assay identified 54 patients with acute and early HIV infection; 99.8% cases with cutoff index ratios ≥50 were proved to be true-positive HIV infection and 95.6% cases with cutoff index ratios <15 were falsely positive. In conclusion, the Elecsys® HIV combi PT assay can identify acute and early HIV infection, including those who might have been missed by third-generation HIV screening assays and Western blot. However, cutoff index ratios <15 are not always false-reactive results; a definitive result cannot be attained without further confirmation. In resource-poor regions where a HIV-1 nucleic acid test may be unaffordable, detection of HIV-1 p24 antigen can be an alternative strategy to diagnose HIV infection in individuals with a negative or indeterminate Western blot.

Clinical Application Evaluation of Two Fourth-Generation Human Immunodeficiency Virus (HIV) Screening Assays in West China Hospital

Fourth-generation human immunodeficiency virus (HIV) screening assays have been used in many laboratories. The Elecsys® HIV combi PT assay is a new kind of fourth-generation HIV screening assay developed to allow earlier detection of seroconversion. A total of 271,845 routine specimens were detected using the Elecsys® HIV combi assay and Elecsys® HIV combi PT assay from September 2010 to December 2012 in a large university hospital. Repeatedly, reactive screening samples were confirmed according to recommended confirmatory algorithms. The false-positive rate and positive predictive value (PPV) of two assays are 0.08 and 78.35%, respectively, for the Elecsys® HIV combi assay and 0.07 and 82.21% for the Elecsys® HIV combi PT assay. Ninety-four percent cases with cutoff index ratio <15.0 were false-positive. When we set the specificity as 95.0 and 99.0%, PPV could increase to 98.7, 99.6, 98.8, and 99.7%, and sensitivity reduced to 99.2, 98.4, 98.5, and 96.8% for the Elecsys® HIV combi assay and the Elecsys® HIV combi PT assay, respectively. The Elecsys® HIV combi PT assay shows a better performance in specificity than the Elecsys® HIV combi assay. Most weakly reactive results were false-positive, this means it still need to be improved and it will need laboratory personnel to communicate with the clinical doctor and patients more properly about the result of the assay.

Validation of the Elecsys® HIV combi PT assay for screening and reliable early detection of HIV-1 infection in Asia

BackgroundThe Elecsys® HIV combi PT assay was developed to allow earlier detection of HIV infection with increased sensitivity and specificity. ObjectivesTo validate the assay for screening and reliable early detection of HIV-1 infection in Asia. Study designSamples tested reflected those routinely screened in Asia and comprised: HIV-1 antigen lysate (25 samples) and antibody (20 samples) dilutions; seven HIV-1 seroconversion panels (46 samples); 39 patient samples from early infection; 183 known-positive sera; HIV-1 p24 antigen sensitivity panel (seven samples); >500 routine clinical samples per center. The Elecsys® HIV combi PT assay was compared with fourth- (ADVIA Centaur® HIV combo, ARCHITECT® HIV combo, Elecsys® HIV combi) and third-generation (VIRONOSTIKA® HIV Uni-Form II Plus O, Zhuhai Livzon Anti-HIV EIA, Serodia® Particle Agglutination) assays commonly used in the region. ResultsOverall, the Elecsys® HIV combi PT showed superior or similar sensitivity to the comparators for detecting all subtypes. The assay correctly identified all positive samples, including those taken soon after infection, and detected seroconversion at a similar or shorter time interval than the comparators. The analytical sensitivity of Elecsys® HIV combi PT for HIV-1 p24 antigen was 0.90IU/mL, which was lower than reported previously. The assay showed good specificity (99.86%) that was superior or equivalent to the other fourth-generation assays tested. ConclusionsThese robust data demonstrate the good subtype inclusivity of the Elecsys® HIV combi PT assay and its suitability for screening and reliable early detection of HIV infection in Asia.

Performance evaluation of a new fourth-generation HIV combination antigen–antibody assay

Education and diagnostic tests capable of early detection represent our most effective means of preventing transmission of human immunodeficiency virus (HIV). The importance of early detection is underlined by studies demonstrating increased life expectancy following early initiation of antiviral treatment. The Elecsys® HIV combi PT assay is a fourth-generation antigen–antibody combination assay developed to allow earlier detection of seroconversion, and to have increased sensitivity and improved specificity. We aimed to determine how early the assay could detect infection compared with existing assays; whether all HIV variants could be detected; and the assay’s specificity using samples from blood donors, routine specimens, and patients with potential cross-reacting factors. Samples were identified as positive by the Elecsys® assay 4.9 days after a positive polymerase chain reaction result (as determined by the panel supplier), which was earlier than the 5.3–7.1 days observed with comparators. The analytical sensitivity of the Elecsys® HIV combi PT assay for the HIV-1 p24 antigen was 1.05 IU/mL, which compares favorably with the comparator assays. In addition, the Elecsys® assay identified all screened HIV subtypes and displayed greater sensitivity to HIV-2 homologous antigen and antibodies to HIV-1 E and O and HIV-2 than the other assays. Overall, the specificity of the Elecsys® assay was 99.88 % using samples from blood donors and 99.81 % when analyzing unselected samples. Potential cross-reacting factors did not interfere with assay performance. The Elecsys® HIV combi PT assay is a sensitive and specific assay that has been granted the CE mark according to Directive 2009/886/EC.