Performance comparison of the Maxim and Sedia Limiting Antigen Avidity assays for HIV incidence surveillance

on behalf of the Consortium for the Evaluation and Performance of HIV Incidence Assays (CEPHIA)

Research output: Contribution to journalArticle

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Abstract

Background Two manufacturers, Maxim Biomedical and Sedia Biosciences Corporation, supply CDCapproved versions of the HIV-1 Limiting Antigen Avidity EIA (LAg) for detecting 'recent' HIV infection in cross-sectional incidence estimation. This study assesses and compares the performance of the two assays for incidence surveillance. Methods We ran both assays on a panel of 2,500 well-characterized HIV-1-infected specimens. We analysed concordance of assay results, assessed reproducibility using repeat testing and estimated mean durations of recent infection (MDRIs) and false-recent rates (FRRs) for a range of normalized optical density (ODn) thresholds, alone and in combination with viral load thresholds. We defined three hypothetical surveillance scenarios, similar to the Kenyan and South African epidemics, and a concentrated epidemic. These scenarios allowed us to evaluate the precision of incidence estimates obtained by means of various recent infection testing algorithms (RITAs) based on each of the two assays. Results The Maxim assay produced lower ODn values than the Sedia assay on average, largely as a result of higher calibrator readings (mean OD of 0.749 vs. 0.643), with correlation of normalized readings lower (R2 = 0.908 vs. R2 = 0.938). Reproducibility on blinded control specimens was slightly better for Maxim. The MDRI of a Maxim-based algorithm at the 'standard' threshold (ODn ≤1.5 & VL >1,000) was 201 days (95% CI: 180,223) and for Sedia 171 (152,191). The difference Differences in MDRI were estimated at 32.7 (22.9,42.8) and 30.9 days (21.7,40.7) for the two algorithms, respectively. Commensurately, the Maxim algorithm had a higher FRR in treatment-naive subjects (1.7% vs. 1.1%). The two assays produced similar precision of incidence estimates in the three surveillance scenarios. Conclusions Differences between the assays can be primarily attributed to the calibrators supplied by the manufacturers. Performance for surveillance was extremely similar, although different thresholds were optimal (i.e. produced the lowest variance of incidence estimates) and at any given ODn threshold, different estimates of MDRI and FRR were obtained. The two assays cannot be treated as interchangeable: assay and algorithm-specific performance characteristic estimates must be used for survey planning and incidence estimation.

Original languageEnglish
Article numbere0220345
JournalPLoS One
Volume14
Issue number7
DOIs
Publication statusPublished - Jan 1 2019

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angle of incidence
Assays
HIV
antigens
Antigens
monitoring
Incidence
assays
Density (optical)
Infection
absorbance
HIV-1
Reading
duration
infection
Human immunodeficiency virus 1
reproducibility
Viral Load
Reproducibility of Results
HIV Infections

ASJC Scopus subject areas

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

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on behalf of the Consortium for the Evaluation and Performance of HIV Incidence Assays (CEPHIA) (2019). Performance comparison of the Maxim and Sedia Limiting Antigen Avidity assays for HIV incidence surveillance. PLoS One, 14(7), [e0220345]. https://doi.org/10.1371/journal.pone.0220345

Performance comparison of the Maxim and Sedia Limiting Antigen Avidity assays for HIV incidence surveillance. / on behalf of the Consortium for the Evaluation and Performance of HIV Incidence Assays (CEPHIA).

In: PLoS One, Vol. 14, No. 7, e0220345, 01.01.2019.

Research output: Contribution to journalArticle

on behalf of the Consortium for the Evaluation and Performance of HIV Incidence Assays (CEPHIA) 2019, 'Performance comparison of the Maxim and Sedia Limiting Antigen Avidity assays for HIV incidence surveillance', PLoS One, vol. 14, no. 7, e0220345. https://doi.org/10.1371/journal.pone.0220345
on behalf of the Consortium for the Evaluation and Performance of HIV Incidence Assays (CEPHIA). Performance comparison of the Maxim and Sedia Limiting Antigen Avidity assays for HIV incidence surveillance. PLoS One. 2019 Jan 1;14(7). e0220345. https://doi.org/10.1371/journal.pone.0220345
on behalf of the Consortium for the Evaluation and Performance of HIV Incidence Assays (CEPHIA). / Performance comparison of the Maxim and Sedia Limiting Antigen Avidity assays for HIV incidence surveillance. In: PLoS One. 2019 ; Vol. 14, No. 7.
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abstract = "Background Two manufacturers, Maxim Biomedical and Sedia Biosciences Corporation, supply CDCapproved versions of the HIV-1 Limiting Antigen Avidity EIA (LAg) for detecting 'recent' HIV infection in cross-sectional incidence estimation. This study assesses and compares the performance of the two assays for incidence surveillance. Methods We ran both assays on a panel of 2,500 well-characterized HIV-1-infected specimens. We analysed concordance of assay results, assessed reproducibility using repeat testing and estimated mean durations of recent infection (MDRIs) and false-recent rates (FRRs) for a range of normalized optical density (ODn) thresholds, alone and in combination with viral load thresholds. We defined three hypothetical surveillance scenarios, similar to the Kenyan and South African epidemics, and a concentrated epidemic. These scenarios allowed us to evaluate the precision of incidence estimates obtained by means of various recent infection testing algorithms (RITAs) based on each of the two assays. Results The Maxim assay produced lower ODn values than the Sedia assay on average, largely as a result of higher calibrator readings (mean OD of 0.749 vs. 0.643), with correlation of normalized readings lower (R2 = 0.908 vs. R2 = 0.938). Reproducibility on blinded control specimens was slightly better for Maxim. The MDRI of a Maxim-based algorithm at the 'standard' threshold (ODn ≤1.5 & VL >1,000) was 201 days (95{\%} CI: 180,223) and for Sedia 171 (152,191). The difference Differences in MDRI were estimated at 32.7 (22.9,42.8) and 30.9 days (21.7,40.7) for the two algorithms, respectively. Commensurately, the Maxim algorithm had a higher FRR in treatment-naive subjects (1.7{\%} vs. 1.1{\%}). The two assays produced similar precision of incidence estimates in the three surveillance scenarios. Conclusions Differences between the assays can be primarily attributed to the calibrators supplied by the manufacturers. Performance for surveillance was extremely similar, although different thresholds were optimal (i.e. produced the lowest variance of incidence estimates) and at any given ODn threshold, different estimates of MDRI and FRR were obtained. The two assays cannot be treated as interchangeable: assay and algorithm-specific performance characteristic estimates must be used for survey planning and incidence estimation.",
author = "{on behalf of the Consortium for the Evaluation and Performance of HIV Incidence Assays (CEPHIA)} and Sempa, {Joseph B.} and Alex Welte and Busch, {Michael P.} and Jake Hall and Dylan Hampton and Facente, {Shelley N.} and Keating, {Sheila M.} and Kara Marson and Neil Parkin and Pilcher, {Christopher D.} and Gary Murphy and Eduard Grebe and Alex Welte and Joseph Sempa and David Matten and Hilmarie Brand and Trust Chibawara and Gary Murphy and Jake Hall and Elaine McKinney and Busch, {Michael P.} and Eduard Grebe and Shelley Facente and Dylan Hampton and Sheila Keating and Mila Lebedeva and Pilcher, {Christopher D.} and Kara Marson and Reshma Kassanjee and Oliver Laeyendecker and Thomas Quinn and David Burns and Susan Little and Anita Sands and Tim Hallett and Owen, {Sherry Michele} and Bharat Parekh and Connie Sexton and Matthew Price and Anatoli Kamali and Lisa Loeb and San Francisco and Jeffrey Martin and Deeks, {Steven G.} and Rebecca Hoh and Zelinda Bartolomei and Natalia Cerqueira and Breno Santos and Capobianchi, {Maria R.} and Barbara Suligoi",
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T1 - Performance comparison of the Maxim and Sedia Limiting Antigen Avidity assays for HIV incidence surveillance

AU - on behalf of the Consortium for the Evaluation and Performance of HIV Incidence Assays (CEPHIA)

AU - Sempa, Joseph B.

AU - Welte, Alex

AU - Busch, Michael P.

AU - Hall, Jake

AU - Hampton, Dylan

AU - Facente, Shelley N.

AU - Keating, Sheila M.

AU - Marson, Kara

AU - Parkin, Neil

AU - Pilcher, Christopher D.

AU - Murphy, Gary

AU - Grebe, Eduard

AU - Welte, Alex

AU - Sempa, Joseph

AU - Matten, David

AU - Brand, Hilmarie

AU - Chibawara, Trust

AU - Murphy, Gary

AU - Hall, Jake

AU - McKinney, Elaine

AU - Busch, Michael P.

AU - Grebe, Eduard

AU - Facente, Shelley

AU - Hampton, Dylan

AU - Keating, Sheila

AU - Lebedeva, Mila

AU - Pilcher, Christopher D.

AU - Marson, Kara

AU - Kassanjee, Reshma

AU - Laeyendecker, Oliver

AU - Quinn, Thomas

AU - Burns, David

AU - Little, Susan

AU - Sands, Anita

AU - Hallett, Tim

AU - Owen, Sherry Michele

AU - Parekh, Bharat

AU - Sexton, Connie

AU - Price, Matthew

AU - Kamali, Anatoli

AU - Loeb, Lisa

AU - Francisco, San

AU - Martin, Jeffrey

AU - Deeks, Steven G.

AU - Hoh, Rebecca

AU - Bartolomei, Zelinda

AU - Cerqueira, Natalia

AU - Santos, Breno

AU - Capobianchi, Maria R.

AU - Suligoi, Barbara

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background Two manufacturers, Maxim Biomedical and Sedia Biosciences Corporation, supply CDCapproved versions of the HIV-1 Limiting Antigen Avidity EIA (LAg) for detecting 'recent' HIV infection in cross-sectional incidence estimation. This study assesses and compares the performance of the two assays for incidence surveillance. Methods We ran both assays on a panel of 2,500 well-characterized HIV-1-infected specimens. We analysed concordance of assay results, assessed reproducibility using repeat testing and estimated mean durations of recent infection (MDRIs) and false-recent rates (FRRs) for a range of normalized optical density (ODn) thresholds, alone and in combination with viral load thresholds. We defined three hypothetical surveillance scenarios, similar to the Kenyan and South African epidemics, and a concentrated epidemic. These scenarios allowed us to evaluate the precision of incidence estimates obtained by means of various recent infection testing algorithms (RITAs) based on each of the two assays. Results The Maxim assay produced lower ODn values than the Sedia assay on average, largely as a result of higher calibrator readings (mean OD of 0.749 vs. 0.643), with correlation of normalized readings lower (R2 = 0.908 vs. R2 = 0.938). Reproducibility on blinded control specimens was slightly better for Maxim. The MDRI of a Maxim-based algorithm at the 'standard' threshold (ODn ≤1.5 & VL >1,000) was 201 days (95% CI: 180,223) and for Sedia 171 (152,191). The difference Differences in MDRI were estimated at 32.7 (22.9,42.8) and 30.9 days (21.7,40.7) for the two algorithms, respectively. Commensurately, the Maxim algorithm had a higher FRR in treatment-naive subjects (1.7% vs. 1.1%). The two assays produced similar precision of incidence estimates in the three surveillance scenarios. Conclusions Differences between the assays can be primarily attributed to the calibrators supplied by the manufacturers. Performance for surveillance was extremely similar, although different thresholds were optimal (i.e. produced the lowest variance of incidence estimates) and at any given ODn threshold, different estimates of MDRI and FRR were obtained. The two assays cannot be treated as interchangeable: assay and algorithm-specific performance characteristic estimates must be used for survey planning and incidence estimation.

AB - Background Two manufacturers, Maxim Biomedical and Sedia Biosciences Corporation, supply CDCapproved versions of the HIV-1 Limiting Antigen Avidity EIA (LAg) for detecting 'recent' HIV infection in cross-sectional incidence estimation. This study assesses and compares the performance of the two assays for incidence surveillance. Methods We ran both assays on a panel of 2,500 well-characterized HIV-1-infected specimens. We analysed concordance of assay results, assessed reproducibility using repeat testing and estimated mean durations of recent infection (MDRIs) and false-recent rates (FRRs) for a range of normalized optical density (ODn) thresholds, alone and in combination with viral load thresholds. We defined three hypothetical surveillance scenarios, similar to the Kenyan and South African epidemics, and a concentrated epidemic. These scenarios allowed us to evaluate the precision of incidence estimates obtained by means of various recent infection testing algorithms (RITAs) based on each of the two assays. Results The Maxim assay produced lower ODn values than the Sedia assay on average, largely as a result of higher calibrator readings (mean OD of 0.749 vs. 0.643), with correlation of normalized readings lower (R2 = 0.908 vs. R2 = 0.938). Reproducibility on blinded control specimens was slightly better for Maxim. The MDRI of a Maxim-based algorithm at the 'standard' threshold (ODn ≤1.5 & VL >1,000) was 201 days (95% CI: 180,223) and for Sedia 171 (152,191). The difference Differences in MDRI were estimated at 32.7 (22.9,42.8) and 30.9 days (21.7,40.7) for the two algorithms, respectively. Commensurately, the Maxim algorithm had a higher FRR in treatment-naive subjects (1.7% vs. 1.1%). The two assays produced similar precision of incidence estimates in the three surveillance scenarios. Conclusions Differences between the assays can be primarily attributed to the calibrators supplied by the manufacturers. Performance for surveillance was extremely similar, although different thresholds were optimal (i.e. produced the lowest variance of incidence estimates) and at any given ODn threshold, different estimates of MDRI and FRR were obtained. The two assays cannot be treated as interchangeable: assay and algorithm-specific performance characteristic estimates must be used for survey planning and incidence estimation.

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