Comparison of 4th-Generation HIV Antigen/Antibody Combination Assay With 3rd-Generation HIV Antibody Assays for the Occurrence of False-Positive and False-Negative Results

Muthukumar, Alagarraju; Alatoom, Adnan; Burns, Susan E.; Ashmore, Jerry; Kim, Anne; Emerson, Brian; Bannister, Edward R.; Ansari, M. Qasim

doi:10.1309/lmm3x37nswucmvrs

Cited by 17 publications

(13 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also detected five acute infections that may have been missed using the thirdgeneration test and algorithm. Similar results for the Architect procedure were recently reported by Muthukumar et al (14). Positive predictive values may be increased further by determining a different cutoff value appropriate for the population to be tested (15).…”

supporting

confidence: 82%

Human Immunodeficiency Virus Diagnostic Testing: 30 Years of Evolution

Alexander

2016

Clin Vaccine Immunol

160

117

View full text Add to dashboard Cite

A concern during the early AIDS epidemic was the lack of a test to identify individuals who carried the virus. The first HIV antibody test, developed in 1985, was designed to screen blood products, not to diagnose AIDS. The first-generation assays detected IgG antibody and became positive 6 to 12 weeks postinfection. False-positive results occurred; thus, a two-test algorithm was developed using a Western blot or immunofluorescence test as a confirmatory procedure. The second-generation HIV test added recombinant antigens, and the third-generation HIV tests included IgM detection, reducing the test-negative window to approximately 3 weeks postinfection. Fourth-and fifth-generation HIV assays added p24 antigen detection to the screening assay, reducing the test-negative window to 11 to 14 days. A new algorithm addressed the fourth-generation assay's ability to detect both antibody and antigen and yet not differentiate between them. The fifth-generation HIV assay provides separate antigen and antibody results and will require yet another algorithm. HIV infection may now be detected approximately 2 weeks postexposure, with a reduced number of false-positive results."

show abstract

supporting

confidence: 82%

Human Immunodeficiency Virus Diagnostic Testing: 30 Years of Evolution

Alexander

2016

Clin Vaccine Immunol

160

117

View full text Add to dashboard Cite

show abstract

“…The use of fourth-generation EIA has been found to have fewer false positives and false negatives and able to detect more acute infections compared to third-generation tests [13]. However, the relatively low proportion of false-negative individuals who had acute HIV infection (10.4% of true positives and 0.09% of RDT negatives) suggests that this was unlikely to be a main factor contributing to the high false-negative rate.…”

Section: Discussionmentioning

confidence: 99%

“…There are multiple factors which can cause or contribute to HIV misdiagnosis. These vary from suboptimal testing strategies (including poor selection of assays used to construct algorithms and use of tiebreakers), deviation from standardized testing algorithms, user errors such as incorrectly performing test procedures, incorrectly interpreting test results, non-adherence to testing standard operating procedures as well as clerical errors [8–13]. False-positive rates as high as 10.3% upon retesting have been observed in some settings [14].…”

Section: Introductionmentioning

confidence: 99%

“…RDTs are second- or third-generation tests capable of detecting HIV-1 envelope protein antibodies, while fourth-generation tests are capable of detecting both antibodies to envelope proteins and p24 antigens [17–19]. The fourth-generation tests have been found to have fewer false positives and false negatives and should be better able to detect HIV infections earlier than third-generation tests [13]. We describe the overall accuracy and performance of the nationally recommended serial RDT algorithm against the nationally recommended laboratory-based fourth-generation immunoassays (IAs) in a household HIV prevalence survey during which rapid HIV testing was offered to willing and consenting participants.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Misdiagnosis of HIV infection during a South African community‐based survey: implications for rapid HIV testing

Kufa

Kharsany

Cawood

et al. 2017

Journal of the International AIDS Society

View full text Add to dashboard Cite

Introduction: We describe the overall accuracy and performance of a serial rapid HIV testing algorithm used in community-based HIV testing in the context of a population-based household survey conducted in two sub-districts of uMgungundlovu district, KwaZulu-Natal, South Africa, against reference fourth-generation HIV-1/2 antibody and p24 antigen combination immunoassays. We discuss implications of the findings on rapid HIV testing programmes. Methods: Cross-sectional design: Following enrolment into the survey, questionnaires were administered to eligible and consenting participants in order to obtain demographic and HIV-related data. Peripheral blood samples were collected for HIV-related testing. Participants were offered community-based HIV testing in the home by trained field workers using a serial algorithm with two rapid diagnostic tests (RDTs) in series. In the laboratory, reference HIV testing was conducted using two fourth-generation immunoassays with all positives in the confirmatory test considered true positives. Accuracy, sensitivity, specificity, positive predictive value, negative predictive value and false-positive and false-negative rates were determined. Results: Of 10,236 individuals enrolled in the survey, 3740 were tested in the home (median age 24 years (interquartile range 19–31 years), 42.1% males and HIV positivity on RDT algorithm 8.0%). From those tested, 3729 (99.7%) had a definitive RDT result as well as a laboratory immunoassay result. The overall accuracy of the RDT when compared to the fourth-generation immunoassays was 98.8% (95% confidence interval (CI) 98.5–99.2). The sensitivity, specificity, positive predictive value and negative predictive value were 91.1% (95% CI 87.5–93.7), 99.9% (95% CI 99.8–100), 99.3% (95% CI 97.4–99.8) and 99.1% (95% CI 98.8–99.4) respectively. The false-positive and false-negative rates were 0.06% (95% CI 0.01–0.24) and 8.9% (95% CI 6.3–12.53). Compared to true positives, false negatives were more likely to be recently infected on limited antigen avidity assay and to report antiretroviral therapy (ART) use. Conclusions: The overall accuracy of the RDT algorithm was high. However, there were few false positives, and the sensitivity was lower than expected with high false negatives, despite implementation of quality assurance measures. False negatives were associated with recent (early) infection and ART exposure. The RDT algorithm was able to correctly identify the majority of HIV infections in community-based HIV testing. Messaging on the potential for false positives and false negatives should be included in these programmes.

show abstract

“…[8][9][10][11][12][13][14][15][16] The use of an HIV assay on a low prevalence population predictably reduces the positive predictive value (PPV) of even an otherwise accurate assay. [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] In light of this, laboratory HIV testing algorithms include confirmatory testing to increase the likelihood that the correct diagnosis is being rendered.…”

mentioning

confidence: 99%

Reducing False-Positive Results With Fourth-Generation HIV Testing at a Veterans Affairs Medical Center

Petersen¹,

Monteiro²,

Dalal³

et al. 2021

Federal Practitioner

View full text Add to dashboard Cite

Background: In 2006, the Centers for Disease Control and Prevention issued guidelines advocating routine HIV screening for all patients. However, false-positive results are a potential patient care threat for low-risk populations even with accurate screening assays. A reduction in HIV falsepositive screening results can potentially be seen by switching from the third-generation to a more sensitive and specific fourth-generation screening assay. Methods: We studied the impact on the false-positive screening rate of a change to a fourth-generation assay at a regional US Department of Veteran Affairs Medical Center. HIV screening tests performed by the laboratory from March 1, 2016 to February 28, 2017, prior to implementation of the new assay were compared with fourth-generation HIV screening tests performed from March 1, 2017 to February 28, 2018.Results: Of 7,516 third-generation HIV screening tests reviewed, 52 were reactive on the screening assay; 24 were true positives, 28 were false positives. The following year 7,802 fourth-generation HIV screening tests were performed and 23 were reactive on the screening assay; 16 were true positives and 7 were false positives. The positive predictive value for the third-generation test was 46% and 70% for the fourth-generation test. Conclusions: There were fewer false-positive results with testing with the more specific fourth-vs third-generation assay (0.09% vs 0.37%, respectively), which was statistically significant (P = .002). This reduction in false-positive screening would reduce the laboratory workload and would save an estimated $3,875 yearly and reduce the adverse effects of false-positive screening results for patients.

show abstract

Comparison of 4th-Generation HIV Antigen/Antibody Combination Assay With 3rd-Generation HIV Antibody Assays for the Occurrence of False-Positive and False-Negative Results

Abstract: This study indicates that the 4th-generation ARCHITECT HIV assay yields fewer false-positive and false-negative results than the 3rd-generation HIV assays we tested.

Cited by 17 publications

References 20 publications

Human Immunodeficiency Virus Diagnostic Testing: 30 Years of Evolution

Human Immunodeficiency Virus Diagnostic Testing: 30 Years of Evolution

Misdiagnosis of HIV infection during a South African community‐based survey: implications for rapid HIV testing

Reducing False-Positive Results With Fourth-Generation HIV Testing at a Veterans Affairs Medical Center

Contact Info

Product

Resources

About