Performance of a limiting-antigen avidity enzyme immunoassay for cross-sectional estimation of HIV incidence in the United States

Jacob Konikoff, Ron Brookmeyer, Andrew F. Longosz, Matthew M. Cousins, Connie Celum, Susan P. Buchbinder, George R. Seage, Gregory D Kirk, Richard D Moore, Shruti Hemendra Mehta, Joseph Bernard Margolick, Joelle Brown, Kenneth H. Mayer, Beryl A. Koblin, Jessica E. Justman, Sally L. Hodder, Thomas C Quinn, Susan Eshleman, Oliver B. Laeyendecker

Research output: Contribution to journalArticle

Abstract

Background: A limiting antigen avidity enzyme immunoassay (HIV-1 LAg-Avidity assay) was recently developed for cross-sectional HIV incidence estimation. We evaluated the performance of the LAg-Avidity assay alone and in multi-assay algorithms (MAAs) that included other biomarkers. Methods and Findings: Performance of testing algorithms was evaluated using 2,282 samples from individuals in the United States collected 1 month to >8 years after HIV seroconversion. The capacity of selected testing algorithms to accurately estimate incidence was evaluated in three longitudinal cohorts. When used in a single-assay format, the LAg-Avidity assay classified some individuals infected >5 years as assay positive and failed to provide reliable incidence estimates in cohorts that included individuals with long-term infections. We evaluated >500,000 testing algorithms, that included the LAg-Avidity assay alone and MAAs with other biomarkers (BED capture immunoassay [BED-CEIA], BioRad-Avidity assay, HIV viral load, CD4 cell count), varying the assays and assay cutoffs. We identified an optimized 2-assay MAA that included the LAg-Avidity and BioRad-Avidity assays, and an optimized 4-assay MAA that included those assays, as well as HIV viral load and CD4 cell count. The two optimized MAAs classified all 845 samples from individuals infected >5 years as MAA negative and estimated incidence within a year of sample collection. These two MAAs produced incidence estimates that were consistent with those from longitudinal follow-up of cohorts. A comparison of the laboratory assay costs of the MAAs was also performed, and we found that the costs associated with the optimal two assay MAA were substantially less than with the four assay MAA. Conclusions: The LAg-Avidity assay did not perform well in a single-assay format, regardless of the assay cutoff. MAAs that include the LAg-Avidity and BioRad-Avidity assays, with or without viral load and CD4 cell count, provide accurate incidence estimates.

Original languageEnglish (US)
Article numbere82772
JournalPLoS One
Volume8
Issue number12
DOIs
StatePublished - Dec 27 2013

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enzyme immunoassays
Immunoenzyme Techniques
Assays
HIV
antigens
Antigens
incidence
Incidence
assays
Enzymes
CD4 Lymphocyte Count
Viral Load
Biomarkers
viral load
HIV Seropositivity
Costs and Cost Analysis
Immunoassay
HIV-1

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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Performance of a limiting-antigen avidity enzyme immunoassay for cross-sectional estimation of HIV incidence in the United States. / Konikoff, Jacob; Brookmeyer, Ron; Longosz, Andrew F.; Cousins, Matthew M.; Celum, Connie; Buchbinder, Susan P.; Seage, George R.; Kirk, Gregory D; Moore, Richard D; Mehta, Shruti Hemendra; Margolick, Joseph Bernard; Brown, Joelle; Mayer, Kenneth H.; Koblin, Beryl A.; Justman, Jessica E.; Hodder, Sally L.; Quinn, Thomas C; Eshleman, Susan; Laeyendecker, Oliver B.

In: PLoS One, Vol. 8, No. 12, e82772, 27.12.2013.

Research output: Contribution to journalArticle

Konikoff, J, Brookmeyer, R, Longosz, AF, Cousins, MM, Celum, C, Buchbinder, SP, Seage, GR, Kirk, GD, Moore, RD, Mehta, SH, Margolick, JB, Brown, J, Mayer, KH, Koblin, BA, Justman, JE, Hodder, SL, Quinn, TC, Eshleman, S & Laeyendecker, OB 2013, 'Performance of a limiting-antigen avidity enzyme immunoassay for cross-sectional estimation of HIV incidence in the United States', PLoS One, vol. 8, no. 12, e82772. https://doi.org/10.1371/journal.pone.0082772
Konikoff, Jacob ; Brookmeyer, Ron ; Longosz, Andrew F. ; Cousins, Matthew M. ; Celum, Connie ; Buchbinder, Susan P. ; Seage, George R. ; Kirk, Gregory D ; Moore, Richard D ; Mehta, Shruti Hemendra ; Margolick, Joseph Bernard ; Brown, Joelle ; Mayer, Kenneth H. ; Koblin, Beryl A. ; Justman, Jessica E. ; Hodder, Sally L. ; Quinn, Thomas C ; Eshleman, Susan ; Laeyendecker, Oliver B. / Performance of a limiting-antigen avidity enzyme immunoassay for cross-sectional estimation of HIV incidence in the United States. In: PLoS One. 2013 ; Vol. 8, No. 12.
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abstract = "Background: A limiting antigen avidity enzyme immunoassay (HIV-1 LAg-Avidity assay) was recently developed for cross-sectional HIV incidence estimation. We evaluated the performance of the LAg-Avidity assay alone and in multi-assay algorithms (MAAs) that included other biomarkers. Methods and Findings: Performance of testing algorithms was evaluated using 2,282 samples from individuals in the United States collected 1 month to >8 years after HIV seroconversion. The capacity of selected testing algorithms to accurately estimate incidence was evaluated in three longitudinal cohorts. When used in a single-assay format, the LAg-Avidity assay classified some individuals infected >5 years as assay positive and failed to provide reliable incidence estimates in cohorts that included individuals with long-term infections. We evaluated >500,000 testing algorithms, that included the LAg-Avidity assay alone and MAAs with other biomarkers (BED capture immunoassay [BED-CEIA], BioRad-Avidity assay, HIV viral load, CD4 cell count), varying the assays and assay cutoffs. We identified an optimized 2-assay MAA that included the LAg-Avidity and BioRad-Avidity assays, and an optimized 4-assay MAA that included those assays, as well as HIV viral load and CD4 cell count. The two optimized MAAs classified all 845 samples from individuals infected >5 years as MAA negative and estimated incidence within a year of sample collection. These two MAAs produced incidence estimates that were consistent with those from longitudinal follow-up of cohorts. A comparison of the laboratory assay costs of the MAAs was also performed, and we found that the costs associated with the optimal two assay MAA were substantially less than with the four assay MAA. Conclusions: The LAg-Avidity assay did not perform well in a single-assay format, regardless of the assay cutoff. MAAs that include the LAg-Avidity and BioRad-Avidity assays, with or without viral load and CD4 cell count, provide accurate incidence estimates.",
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AU - Longosz, Andrew F.

AU - Cousins, Matthew M.

AU - Celum, Connie

AU - Buchbinder, Susan P.

AU - Seage, George R.

AU - Kirk, Gregory D

AU - Moore, Richard D

AU - Mehta, Shruti Hemendra

AU - Margolick, Joseph Bernard

AU - Brown, Joelle

AU - Mayer, Kenneth H.

AU - Koblin, Beryl A.

AU - Justman, Jessica E.

AU - Hodder, Sally L.

AU - Quinn, Thomas C

AU - Eshleman, Susan

AU - Laeyendecker, Oliver B.

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N2 - Background: A limiting antigen avidity enzyme immunoassay (HIV-1 LAg-Avidity assay) was recently developed for cross-sectional HIV incidence estimation. We evaluated the performance of the LAg-Avidity assay alone and in multi-assay algorithms (MAAs) that included other biomarkers. Methods and Findings: Performance of testing algorithms was evaluated using 2,282 samples from individuals in the United States collected 1 month to >8 years after HIV seroconversion. The capacity of selected testing algorithms to accurately estimate incidence was evaluated in three longitudinal cohorts. When used in a single-assay format, the LAg-Avidity assay classified some individuals infected >5 years as assay positive and failed to provide reliable incidence estimates in cohorts that included individuals with long-term infections. We evaluated >500,000 testing algorithms, that included the LAg-Avidity assay alone and MAAs with other biomarkers (BED capture immunoassay [BED-CEIA], BioRad-Avidity assay, HIV viral load, CD4 cell count), varying the assays and assay cutoffs. We identified an optimized 2-assay MAA that included the LAg-Avidity and BioRad-Avidity assays, and an optimized 4-assay MAA that included those assays, as well as HIV viral load and CD4 cell count. The two optimized MAAs classified all 845 samples from individuals infected >5 years as MAA negative and estimated incidence within a year of sample collection. These two MAAs produced incidence estimates that were consistent with those from longitudinal follow-up of cohorts. A comparison of the laboratory assay costs of the MAAs was also performed, and we found that the costs associated with the optimal two assay MAA were substantially less than with the four assay MAA. Conclusions: The LAg-Avidity assay did not perform well in a single-assay format, regardless of the assay cutoff. MAAs that include the LAg-Avidity and BioRad-Avidity assays, with or without viral load and CD4 cell count, provide accurate incidence estimates.

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