scholarly journals Reduction of Diagnostic Window by New Fourth-Generation Human Immunodeficiency Virus Screening Assays †

1998 ◽  
Vol 36 (8) ◽  
pp. 2235-2239 ◽  
Author(s):  
Bernard Weber ◽  
El Hadji Mbargane Fall ◽  
Annemarie Berger ◽  
Hans Wilhelm Doerr
Keyword(s):  
Hiv Infection ◽  
Fourth Generation ◽  
Third Generation ◽  
Serum Samples ◽  
Immunodeficiency Virus ◽  
Hiv Antigen ◽  
Diagnostic Window ◽  
P24 Antigen ◽  
Culture Supernatants ◽  
Hiv 1

In order to reduce the diagnostic window between the time of human immunodeficiency virus (HIV) infection and laboratory diagnosis, new screening enzyme-linked immunosorbent assays (ELISAs) which permit the simultaneous detection of HIV antigen and antibody have been developed. Two fourth-generation assays, HIV DUO (Biomérieux) and HIV Combi (Boehringer Mannheim), for the combined detection of HIV antigen and antibody, were compared with a third-generation assay (HIV-1/HIV-2 3rd Generation Plus enzyme immunoassay [EIA]; Abbott) and a p24 antigen test (HIV-1 Ag monoclonal; Abbott). A total of 17 seroconversion panels, 15 cell culture supernatants infected with different HIV type 1 (HIV-1) subtypes, and 255 potentially cross-reactive serum samples were tested. Ten seroconversions were detected an average of 8.1 days earlier with HIV DUO and 7.5 days earlier with HIV Combi than with the third-generation ELISA. Overall, in the 17 seroconversion panels tested, HIV DUO detected HIV-1 infection an average of 4.8 days and HIV Combi detected infection an average of 4.4 days earlier than HIV-1/HIV-2 3rd Generation Plus EIA. HIV antigen was detected with HIV DUO and HIV Combi in all of the 15 cell culture supernatants infected with different HIV-1 subtypes, including subtype O. With fourth-generation assays, considerably fewer false-positive results (n = 4 to 6) were obtained, in comparison with the third-generation EIA (n = 18). Fourth-generation assays permit an earlier diagnosis of HIV infection than third-generation antibody screening assays through the detection of p24 antigen, which may be present in serum samples from individuals with recent HIV infection prior to seroconversion.

Laboratory Diagnosis and Monitoring of HIV Infection

2019 ◽  
Author(s):  
Anna Jeffery- Smith ◽  
C. Y. William Tong
Keyword(s):  
Hiv Infection ◽  
Sensitivity And Specificity ◽  
Point Of Care ◽  
Fourth Generation ◽  
Third Generation ◽  
Window Period ◽  
P24 Antigen ◽  
Exposure Risks ◽  
Positive Results ◽  
Hiv 1

In the majority of UK laboratories initial testing for HIV is now performed using a fourth generation test, which is a combination test for antibody to HIV and p24 antigen. These tests should be able to detect antibody to both HIV-1 and HIV-2. In addition, due to the heterogeneity of the virus they should be able to reliably detect antibody to the main circulating subtypes of HIV-1, i.e. group M (Major), O (Outlier), and N (non-M, non-O). The p24 antigen is an HIV capsid protein which is produced in large quantities during initial infection, prior to seroconversion. The sensitivity and specificity of fourth generation tests is typically > 99%. However, all positive results need further confirmation tests, as discussed below. Third generation laboratory assays only test for the presence of antibody to HIV. Though it includes the detection of IgM (which is not included in second generation assays), they do not detect early infection with isolated HIV antigen prior to seroconversion. Point-of-care testing for HIV is performed in the clinic or at bedside. Like laboratory based assays these tests can be either third or fourth generation. The sensitivity and specificity of point-of-care tests is considered lower than that of laboratory tests, and all positive results require confirmation with a laboratory assay. The window period is the length of time following infection with HIV until the appearance of laboratory markers of HIV infection in the blood. This period varies depending on which marker, i.e. antibody or antigen, is being tested for. The window period for fourth-generation tests is between eleven days and one month. Patients being counselled prior to this testing should be advised that a negative result does not cover risk exposures in the preceding month. These patients should be advised to have repeat testing if they have any further exposure risks in the preceding month prior to testing. For third-generation tests the window period is up to three months, correlating with the amount of time it may take for antibodies to HIV to develop.

Immunocytochemical identification of HIV (p24) antigen in parotid lymphoid lesions

1989 ◽  
Vol 103 (11) ◽  
pp. 1063-1066 ◽  
Author(s):  
J. M. Bruner ◽  
K. R. Cleary ◽  
F. B. Smith ◽  
J. G. Batsakis
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Lymphoid Cells ◽  
Gag Protein ◽  
Laboratory Markers ◽  
Immunodeficiency Virus ◽  
Lymphoepithelial Cysts ◽  
Patients At Risk ◽  
P24 Antigen ◽  
Hiv 1

AbstractAntibodies to specific human immunodeficiency virus (HIV) polypeptides are important laboratory markers of HIV infection. We have used an antibody to the major structural gag protein p24 of HIV-1 virus to immunochemically localize this capsid antigen in lymphoid cells from seven of eight patients at risk for HIV infection and who presented with parotid lymphadenopathy and lymphoepithelial cysts of the parotid gland. A clinicopathological assessment of these two manifestations as they relate to HIV infection is also presented.

scholarly journals Assessment of a new "DS-EIA-HIV-AB-TERM" assay to determine the probable time of infection with human immunodeficiency virus-1 (HIV-1)

2015 ◽  
Vol 20 (3) ◽  
pp. 23-27
Author(s):  
Yu. E Zagryadskaya ◽  
D. A Neshumaev ◽  
Yu. A Kokotyukha ◽  
E. M Meyrmanova ◽  
I. A Olkhovskiy ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Population Level ◽  
Test System ◽  
Serum Samples ◽  
Immunodeficiency Virus ◽  
Time Of Infection ◽  
Hiv 1 ◽  
Probable Time

The epidemiological situation for HIV infection in Russia remains to be extremely stringent, which requires a search for new, more efficient and cost-effective solutions aimed at countering the epidemic. The inclusion of laboratory studies with the use of a test system for the determination of the remoteness of HIV infection in routine surveillance practices will permit to determine the frequency of occurrence of early cases of infections among newly diagnosed HIV-positive persons. The analysis of this criterion at the population level will help to objectively evaluate the effectiveness of prevention, control activities carried out in a particular area. The increase of objectivity in the determination of the time elapsed from the moment of infection of HIV-1 with the use of the test system DSEIA-HIV-Ab-TERM provides the opportunity to use the obtained results in the epidemiological investigation for the purpose of more accurate and complete identification of contact persons. The determination of the probable period of infection may also be required in the solving the question on the prescription of antiretroviral therapy as a complementary study in the monitoring of HIV drug resistance. The aim of this work was to determine the effectiveness of the new test system DS-EIAHIV-Ab-TERM for the determination of the likely timing of HIV-1 infection. There were studied serum samples (plasma) of blood of HIV-infected persons with epidemiologically established time of infection (n = 281) and samples of commercial seroconversion panels. Results of the performed study showed that the probability of a correct detection of the remoteness of HIV-1 infection for samples from individuals with the most probable time of the established fact of infection was 95%, for samples of commercial seroconversion panels - 100%. The data demonstrated the high efficacy of the test system DS-“EIAHIV-Ab-TERM” in the determination of the most probable timing of infection with human immunodeficiency virus type 1, that in combination with the speed and simplicity of the procedure allows to recommend it for use in the laboratory practice.

The performance of the Alere HIV combo point-of-care test on stored serum samples; useful for detection of early HIV-1 infections?

2017 ◽  
Vol 94 (5) ◽  
pp. 331-333 ◽  
Author(s):  
Carla van Tienen ◽  
Sharona Rugebregt ◽  
Sandra Scherbeijn ◽  
Hannelore Götz ◽  
Corine Geurts van Kessel
Keyword(s):  
Hiv Infection ◽  
Point Of Care ◽  
Acute Infection ◽  
Rapid Test ◽  
Public Health Department ◽  
Laboratory Setting ◽  
Serum Samples ◽  
Point Of Care Test ◽  
P24 Antigen ◽  
Hiv 1

IntroductionThe Alere HIV-1/2 Antigen/Antibody Combo point-of-care test is a commercially available 4th-generation rapid test for the diagnosis of HIV infection, including acute infection. We evaluated the sensitivity of this test in samples from patients with acute, recent or chronic HIV-1 infection.MethodsA validation of the test was performed using 89 HIV-positive serum samples collected in 2008–2016, that were stored at −20°C. Twenty-three samples were only p24-positive (acute infection); 49 samples were antibody-positive and p24-positive (recent infection); 17 samples were only antibody-positive (chronic infection). HIV infection was confirmed by standard-of-care assays and PCR. Samples came from patients attending an outpatient clinic for STDs at the Public Health Department and from patients within the Erasmus Medical Center, Rotterdam, the Netherlands.ResultsThe overall sensitivity of the test for diagnosing HIV infection based on detection of p24 antigen and/or antibodies was 92% (95% CI 86% to 98%) (82/89). In acute sera with only p24 antigen positivity, the sensitivity of the test decreased to 65% (95% CI 46% to 85%) (15/23). When both antibody and antigen testing were positive, the p24 sensitivity was only 24% (95% CI 12% to 36%) (12/49), but in these sera the final test result was positive in all sera (49/49) due to the positive antibody component.ConclusionsIn a laboratory setting, this test has an overall sensitivity of 92% to detect any stage of HIV-1 infection using sera specimens. It performs relatively well in detecting early HIV and may be beneficial as an initial screening in patients with a recent exposure to HIV. Additional testing in a laboratory setting remains mandatory as a proportion of acute HIV-1 infections are missed with this test.

scholarly journals Integrated analysis of lncRNA, miRNA and mRNA profiles reveals potential lncRNA functions during early HIV infection

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lianwei Ma ◽  
Hui Zhang ◽  
Yue Zhang ◽  
Hailong Li ◽  
Minghui An ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Immune Activation ◽  
Expression Profiles ◽  
Critical Role ◽  
Differentially Expressed ◽  
Integrated Analysis ◽  
Target Mrnas ◽  
Immunodeficiency Virus ◽  
Mirna Sequencing ◽  
Hiv 1

Abstract Background Long noncoding RNAs (lncRNAs) can regulate gene expression in a cis-regulatory fashion or as “microRNA sponges”. However, the expression and functions of lncRNAs during early human immunodeficiency virus (HIV) infection (EHI) remain unclear. Methods 3 HAART-naive EHI patients and 3 healthy controls (HCs) were recruited in this study to perform RNA sequencing and microRNA (miRNA) sequencing. The expression profiles of lncRNAs, mRNAs and miRNAs were obtained, and the potential roles of lncRNAs were analysed based on discovering lncRNA cis-regulatory target mRNAs and constructing lncRNA–miRNA–mRNA competing endogenous RNA (ceRNA) networks. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on 175 lncRNA-associated differentially expressed (DE) mRNAs to investigate the potential functions of DE lncRNAs in ceRNA networks. Results A total of 242 lncRNAs, 1240 mRNAs and 21 mature known miRNAs were determined as differentially expressed genes in HAART-naive EHI patients compared to HCs. Among DE lncRNAs, 44 lncRNAs were predicted to overlap with 41 target mRNAs, and 107 lncRNAs might regulate their nearby DE mRNAs. Two DE lncRNAs might regulate their cis-regulatory target mRNAs BTLA and ZAP70, respectively, which were associated with immune activation. In addition, the ceRNA networks comprised 160 DE lncRNAs, 21 DE miRNAs and 175 DE mRNAs. Seventeen DE lncRNAs were predicted to regulate HIF1A and TCF7L2, which are involved in the process of HIV-1 replication. Twenty DE lncRNAs might share miRNA response elements (MREs) with FOS, FOSB and JUN, which are associated with both immune activation and HIV-1 replication. Conclusions This study revealed that lncRNAs might play a critical role in HIV-1 replication and immune activation during EHI. These novel findings are helpful for understanding of the pathogenesis of HIV infection and provide new insights into antiviral therapy.

scholarly journals Acute Infections, Cost per Infection and Turnaround Time in Three United States Hospital Laboratories Using Fourth-Generation Antigen-Antibody Human Immunodeficiency Virus Immunoassays

2015 ◽  
Vol 3 (1) ◽  
Author(s):  
Laura G. Wesolowski ◽  
Muazzam Nasrullah ◽  
Robert W. Coombs ◽  
Eric Rosenberg ◽  
Steven F. Ethridge ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
South Carolina ◽  
Massachusetts General Hospital ◽  
Medical Center ◽  
Fourth Generation ◽  
Reference Laboratory ◽  
Acute Infections ◽  
Immunodeficiency Virus ◽  
Antigen Antibody ◽  
Hiv 1

Abstract Background.  To improve clinical and public health outcomes through early human immunodeficiency virus (HIV) detection, fourth-generation antigen/antibody immunoassay (4IA) and supplemental testing results must be returned rapidly. Methods.  We examined HIV testing data at Harborview Medical Center (HMC), Massachusetts General Hospital (MGH), and the Medical University of South Carolina (MUSC), which used 4IA and supplemental antibody and nucleic acid tests (NATs). At MGH and MUSC, HIV-1 Western blot (WB) and HIV-2 testing were conducted at a reference laboratory. We compared time from specimen collection to laboratory result for established (positive WB) and acute infections (reactive 4IA, negative/indeterminate WB, detectable NAT), and we calculated testing cost per positive-test result. Results.  From 3731 (MUSC) to 19 774 (MGH) tests were conducted; 0.01% (MGH) to 0.05% (HMC) were acute infections. Each laboratory had reactive 4IA, WB-negative, or indeterminate specimens without NAT (ie, potential acute infections). Time to result was 1.5 (HMC) to 5.2 days (MGH) for acute and 1.0 (HMC) to 5.2 days (MGH) for established infections. Costs were $1054 (MGH) to $1521 (MUSC). Conclusions.  Conducting supplemental testing in-house lowered turnaround times, which may be further reduced with rapid HIV-1/HIV-2 differentiation tests. Hospitals may benefit from quantitative NATs not requiring physician orders, so all potential acute infections receive NAT.

scholarly journals Streptavidin-conjugated gold nanoclusters as ultrasensitive fluorescent sensors for early diagnosis of HIV infection

2018 ◽  
Vol 4 (11) ◽  
pp. eaar6280 ◽  
Author(s):  
Aditya Dileep Kurdekar ◽  
L. A. Avinash Chunduri ◽  
C. Sai Manohar ◽  
Mohan Kumar Haleyurgirisetty ◽  
Indira K. Hewlett ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Limit Of Detection ◽  
Gold Nanoclusters ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Metal Nanoclusters ◽  
Detection Range ◽  
In Silico Studies ◽  
P24 Antigen ◽  
Hiv 1

We have engineered streptavidin-labeled fluorescent gold nanoclusters to develop a gold nanocluster immunoassay (GNCIA) for the early and sensitive detection of HIV infection. We performed computational simulations on the mechanism of interaction between the nanoclusters and the streptavidin protein via in silico studies and showed that gold nanoclusters enhance the binding to the protein, by enhancing interaction between the Au atoms and the specific active site residues, compared to other metal nanoclusters. We also evaluated the role of glutathione conjugation in binding to gold nanoclusters with streptavidin. As proof of concept, GNCIA achieved a sensitivity limit of detection of HIV-1 p24 antigen in clinical specimens of 5 pg/ml, with a detection range up to1000 pg/ml in a linear dose-dependent manner. GNCIA demonstrated a threefold higher sensitivity and specificity compared to enzyme-linked immunosorbent assay for the detection of HIV p24 antigen. The specificity of the immunoassay was 100% when tested with plasma samples negative for HIV-1 p24 antigen and positive for viruses such as hepatitis B virus, hepatitis C virus, and dengue. GNCIA could be developed into a universal labeling technology using the relevant capture and detector antibodies for the specific detection of antigens of various pathogens in the future.

scholarly journals Interleukin 7 Increases Human Immunodeficiency Virus Type 1 LAI-Mediated Fas-Induced T-Cell Death

2005 ◽  
Vol 79 (5) ◽  
pp. 3195-3199 ◽  
Author(s):  
Jean-Daniel Lelièvre ◽  
Frédéric Petit ◽  
Damien Arnoult ◽  
Jean-Claude Ameisen ◽  
Jérôme Estaquier
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
Hiv Infection ◽  
Cell Infection ◽  
Interleukin 7 ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Fas-mediated T-cell death is known to occur during human immunodeficiency virus (HIV) infection. In this study, we found that HIV type 1 LAI (HIV-1LAI) primes CD8+ T cells from healthy donors for apoptosis, which occurs after Fas ligation. This effect is counteracted by a broad caspase inhibitor (zVAD-fmk). Fas-mediated cell death does not depend on CD8+ T-cell infection, because it occurred in the presence of reverse transcriptase inhibitors. However, purified CD8+ T cells are sensitive to Fas only in the presence of soluble CD4. Finally, we found that interleukin 7 (IL-7) increases Fas-mediated CD4+ and CD8+ T-cell death induced by HIV-1LAI. Since high levels of IL-7 are a marker of poor prognosis during HIV infection, our data suggest that enhancement of Fas-mediated T-cell death by HIV-1LAI and IL-7 is one of the mechanisms involved in progression to AIDS.

scholarly journals Early Detection of Human Immunodeficiency Virus Type 1-Specific B-Lymphocyte-Derived Antibodies in a High-Risk Population

2009 ◽  
Vol 16 (7) ◽  
pp. 1060-1065 ◽  
Author(s):  
Odd Odinsen ◽  
David Parker ◽  
Frans Radebe ◽  
Mikey Guness ◽  
David A Lewis
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Load ◽  
B Cell ◽  
Immunodeficiency Virus ◽  
Hiv Antibodies ◽  
P24 Antigen ◽  
Anti Hiv ◽  
Hiv 1

ABSTRACT Diagnosis of acute human immunodeficiency virus (HIV) infection, a key driver of the HIV epidemic, remains a public health challenge. The PlasmAcute technology offers an opportunity to detect early anti-HIV antibody responses. B lymphocytes (B cells) were isolated from the blood of seronegative miners in South Africa by using the PlasmAcute method. B-cell lysates and paired sera were tested for anti-HIV-1 antibodies by two different enzyme-linked immunosorbent assays; immunoreactivity was confirmed by Western blotting. All volunteers were tested for HIV type 1 (HIV-1) viral load, p24 antigen, and CD4 count. Sera from HIV-seronegative men who had positive viral loads and were positive for p24 antigen were retested for anti-HIV antibodies after immune complex dissociation. Anti-HIV antibodies were detected in lysates from 16/259 subjects without immunoreactivity in paired sera. Four subjects, one of whom had a positive viral load initially, subsequently seroconverted. Six subjects showed transient anti-HIV-1 antibodies in the lysates and tested negative for all markers at the follow-up. Five subjects without follow-up data initially had lysate-positive/serum-negative samples, and these cases were classified as inconclusive. One subject had lysate antibodies and a detectable viral load but was seronegative at follow-up. In conclusion, lysate-derived anti-HIV-1 B-cell antibodies can be detected prior to seroconversion and earlier than or contemporary with HIV-1 RNA detection.

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