Home HIV avidity index performance using a modified fourth-generation immunoassay to detect recent HIV infections
Article
Licensed
Unlicensed Requires Authentication

HIV avidity index performance using a modified fourth-generation immunoassay to detect recent HIV infections

  • Barbara Suligoi EMAIL logo , Vincenza Regine , Mariangela Raimondo , Anna Rodella , Luigina Terlenghi , Arnaldo Caruso , Patrizia Bagnarelli , Maria Rosaria Capobianchi , Nadia Zanchetta , Valeria Ghisetti and Claudio Galli
Published/Copyright: June 24, 2017
Become an author with De Gruyter Brill
Submit Manuscript Author Information
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 55 Issue 12

Abstract

Background:

Detecting recent HIV infections is important to evaluate incidence and monitor epidemic trends. We aimed to evaluate the diagnostic performance and accuracy of the avidity index (AI) for discriminating for recent HIV infections.

Methods:

We collected serum samples from HIV-1 positive individuals: A) with known date of infection (midpoint in time between last HIV-negative and first HIV-positive test); B) infected for >1 year. Samples were divided into two aliquots: one diluted with phosphate buffered saline (PBS) and the other with 1 M guanidine. Both aliquots were assayed by the Architect HIV Ag/Ab Combo 4th generation assay (Abbott). We compared AI found in recent (RI=<6 months from seroconversion) and established (EI) infections. The diagnostic accuracy was evaluated by receiver operating characteristic (ROC) curve analysis. The proportion of samples misclassified as recent (FRR) was calculated.

Results:

In total, 647 samples were collected: 455 in group A (51.6% RI and 48.4% EI) and 192 in group B. Among these, sixteen samples were from elite controllers, 294 from treated patients, 328 from patients infected with non-B subtypes. Samples before antiretroviral initiation showed a mean AI significantly lower among RI compared to EI (0.66+0.28 vs. 1.00±0.12; p<0.000). The FRR was 0% using a cut-off of ≤0.70. An extremely low FRR was observed among elite controllers, samples with low VL or CD4. HIV subtype had no impact on AI misclassifications. All individuals in group A reached the AI threshold of 0.80 within 24 months after seroconversion.

Conclusions:

The AI is an accurate serological marker for discriminating recent from established HIV infections and meets WHO requirements for HIV incidence assays.

Keywords: avidity; enzyme immunoassay; epidemiology; HIV; incidence; recent infection
Corresponding author: Barbara Suligoi, MD, Department of Infectious Diseases,Istituto Superiore di Sanità, Viale Regina Elena 299 – 00161 Rome, Italy, Phone: +39 0649906123, Fax: +39 0649902755

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This study was partly funded by the Italian Ministry of Health, Ricerca Corrente.

  3. Employment or leadership: Claudio Galli is currently employed by Abbott Diagnostics as the Associate Medical Director for Europe.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Smith MK, Rutstein SE, Powers KA, Fidler S, Miller WC, Eron JJ, et al. The detection and management of early HIV infection: a clinical and public health emergency. J Acquir Immune Defic Syndr 2013;63:S187–99.10.1097/QAI.0b013e31829871e0Search in Google Scholar PubMed PubMed Central

2. UNAIDS/WHO Working Group on Global HIV/AIDS and STI Surveillance. When and how to use assays for recent infection to estimate HIV incidence at a population level. World Health Organisation; 2011. Available from: http://www.who.int/diagnostics_laboratory/hiv_incidence_may13_final.pdf.Search in Google Scholar

3. Murphy G, Parry JV. Assays for the detection of recent infections with human immunodeficiency virus type 1. Eurosurveillance 2008;13:4–10.10.2807/ese.13.36.18966-enSearch in Google Scholar

4. Cole KS, Murphey-Corb M, Narayan O, Joag SV, Shaw GM, Montelaro RC. Common themes of antibody maturation to simian immunodeficiency virus, simian-human immunodeficiency virus and human immunodeficiency virus type 1 infections. J Virol 1998;72:7852–9.10.1128/JVI.72.10.7852-7859.1998Search in Google Scholar PubMed PubMed Central

5. Curdt I, Praast G, Sickinger E, Schultess J, Herold I, Braun HB, et al. Development of fully automated determination of marker-specific immunoglobulin G (IgG) avidity based on the avidity competition assay format: application for the Abbott Architect cytomegalovirus and Toxo IgG avidity assays. J Clin Microbiol 2009;47:603–13.10.1128/JCM.01076-08Search in Google Scholar PubMed PubMed Central

6. Suligoi B, Massi M, Galli C, Sciandra M, Di Sora F, Pezzotti P, et al. Identifying recent HIV infections using the avidity index and an automated enzyme immunoassay. J Acquir Immune Defic Syndr 2003;32:424–8.10.1097/00126334-200304010-00012Search in Google Scholar PubMed

7. Suligoi B, Buttò S, Galli C, Bernasconi D, Salata RA, Tavoschi L, et al. Detection of recent HIV infections in African individuals infected by HIV-1 non-B subtypes using HIV antibody avidity. J Clin Virol 2008;41:288–92.10.1016/j.jcv.2007.11.020Search in Google Scholar PubMed

8. Suligoi B, Raimondo M, Regine V, Rodella A, Terlenghi L, Bagnarelli P, et al. HIV avidity index for identifying recent HIV infections: factors associated with false recent classification. Clin Chem Lab Med 2015;53:S1323.Search in Google Scholar

9. Suligoi B, Rodella A, Raimondo M, Regine V, Terlenghi L, Manca N, et al. Avidity Index for anti-HIV antibodies: comparison between third- and fourth-generation automated immunoassays. J Clin Microbiol 2011;49:2610–3.10.1128/JCM.02115-10Search in Google Scholar PubMed PubMed Central

10. CDC: Guidelines for the use of antiretroviral agents in HIV-1–infected adults and adolescents, US Department of Health and Human Services. AIDSinfo 2016. Available from: https://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf.Search in Google Scholar

11. World Health Organization. WHO/UNAIDS annual meeting of the technical Working Group on HIV Incidence Assays, October 2014. WHO/HIV/2015.11. Available from: http://apps.who.int/iris/bitstream/10665/162156/1/WHO_HIV_2015.11_eng.pdf?ua=1&ua=1.Search in Google Scholar

12. Buttò S, Raimondo M, Fanales-Belasio E, Suligoi B. Suggested strategies for the laboratory diagnosis of HIV infection in Italy. Ann Ist Super Sanita 2010;46:34–41.10.1590/S0021-25712010000100005Search in Google Scholar

13. NCCLS. Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline-Second Edition, 2004.Search in Google Scholar

14. Selleri M, Orchi N, Zaniratti MS, Bellagamba R, Corpolongo A, Angeletti C, et al. Effective highly active antiretroviral therapy in patients with primary HIV-1 infection prevents the evolution of the avidity of HIV-1-specific antibodies. J Acquir Immune Defic Syndr 2007;46:145–50.10.1097/QAI.0b013e318120039bSearch in Google Scholar PubMed

15. Binley JM, Trkola A, Ketas T, Schiller D, Clas B, Little S, et al. The effect of highly active antiretroviral therapy on binding and neutralizing antibody responses to human immunodeficiency virus type 1 infection. Journal of Infectious Diseases 2000;182:945–9.10.1086/315774Search in Google Scholar PubMed

16. Kassanjee R, Pilcher CD, Keating SM, Facente SN, Mckinney E, Price MA, et al. Independent assessment of candidate HIV incidence assays on specimens in the CEPHIA repository. AIDS 2014;28:2439–49.10.1097/QAD.0000000000000429Search in Google Scholar PubMed PubMed Central

17. Kirkpatrick AR, Patel EU, Celum CL, Moore RD, Blankson JM, Mehta SH, et al. Development and evaluation of a modified fourth-generation human immunodeficiency virus enzyme immunoassay for cross-sectional incidence estimation in clade B populations. AIDS Res Hum Retroviruses 2016;32:756–62.10.1089/aid.2015.0198Search in Google Scholar PubMed PubMed Central

18. Kassanjee R, Pilcher CD, Busch MP, Murphy G, Facente SN, Keating SM, et al. Viral load criteria and threshold optimization to improve HIV incidence assay characteristics. AIDS 2016;30:2361–71.10.1097/QAD.0000000000001209Search in Google Scholar PubMed PubMed Central

19. Curtis KA, Hanson DL, Kennedy MS, Owen M. Evaluation of a multiplex assay for estimation of HIV-1 incidence. PLoS One 2013;8:e64201.10.1371/journal.pone.0064201Search in Google Scholar PubMed PubMed Central

20. Laeyendecker O, Brookmeyer R, Oliver AE, Mullis CE, Eaton KP, Mueller AC, et al. Factors associated with incorrect identification of recent HIV infection using the BED capture immunoassay. AIDS Res Hum Retroviruses 2012;28:816–22.10.1089/aid.2011.0258Search in Google Scholar PubMed PubMed Central

21. Jafarzadeh SR, Johnson WO, Gardner IA. Bayesian modelling and inference for diagnostic accuracy and probability of disease based on multiple diagnostic biomarkers with and without a perfect reference standard. Stat Med 2016;35:859–76.10.1002/sim.6745Search in Google Scholar PubMed

22. Hanson DL, Song R, Masciotra S, Hernandez A, Dobbs TL, Parekh B, et al. Mean recency period for estimation of HIV-1 incidence by the BED-capture EIA and Bio-Rad avidity in persons diagnosed in the United States with subtype B. PLoS One 2016;11:e0152327.10.1371/journal.pone.0152327Search in Google Scholar PubMed PubMed Central

23. Sweeting MJ, De Angelis D, Parry J, Suligoi B. Estimating the distribution of the window period for recent HIV infections: a comparison of statistical methods. Stat Med 2010;29:3194–202.10.1002/sim.3941Search in Google Scholar PubMed PubMed Central

24. Shepherd SJ, McAllister G, Kean J, Wallace LA, Templeton KE, Goldberg DJ, et al. Development of an avidity assay for detection of recent HIV infections. J Virol Methods 2015;217:42–9.10.1016/j.jviromet.2015.02.016Search in Google Scholar PubMed

25. European Centre for Disease Prevention and Control/WHO Regional Office for Europe. HIV/AIDS surveillance in Europe 2013. Stockholm: ECDC, 2014.Search in Google Scholar

26. Ministero della Salute, Sezioni L ed M del Comitato Tecnico Sanitario. Linee Guida Italiane sull’utilizzo dei farmaci antiretrovirali e sulla gestione diagnostico-clinica delle persone con infezione da HIV-1. 17 Dicembre 2015. Available from: http://www.simit.org/medias/852-lg-hiv-2015-c17pubblicazioni2442allegato.pdf.Search in Google Scholar

27. EACS: European AIDS Clinical Society. Guidelines, version 8.0, October 2015. Available from: http://www.eacsociety.org/guidelines/eacs-guidelines/eacs-guidelines.html.Search in Google Scholar

Supplemental Material:

The online version of this article (https://doi.org/10.1515/cclm-2016-1192) offers supplementary material, available to authorized users.

Received: 2016-12-29
Accepted: 2017-5-5
Published Online: 2017-6-24
Published in Print: 2017-10-26

©2017 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Tumor microenvironment and systemic disease: a dual target in medical oncology (also in the case of biomarkers)
  4. Reviews
  5. Sample types applied for molecular diagnosis of therapeutic management of advanced non-small cell lung cancer in the precision medicine
  6. The impact of pneumatic tube system on routine laboratory parameters: a systematic review and meta-analysis
  7. Opinion Paper
  8. How to reduce scientific irreproducibility: the 5-year reflection
  9. EFLM Paper
  10. Strategies to define performance specifications in laboratory medicine: 3 years on from the Milan Strategic Conference
  11. General Clinical Chemistry and Laboratory Medicine
  12. Intensive educational efforts combined with external quality assessment improve the preanalytical phase in general practitioner offices and nursing homes
  13. Separate patient serum sodium medians from males and females provide independent information on analytical bias
  14. Are admission procalcitonin levels universal mortality predictors across different medical emergency patient populations? Results from the multi-national, prospective, observational TRIAGE study
  15. Biochemical testing in a laboratory tent and semi-intensive care of Ebola patients on-site in a remote part of Guinea: a paradigm shift based on a bleach-sensitive point-of-care device
  16. Efficient reporting of the estimated glomerular filtration rate without height in pediatric patients with cancer
  17. Evaluation of thyroid test utilization through analysis of population-level data
  18. Relation of serum γ-glutamyl transferase activity with copper in an adult population
  19. Impact of a single oral dose of 100,000 IU vitamin D3 on profiles of serum 25(OH)D3 and its metabolites 24,25(OH)2D3, 3-epi-25(OH)D3, and 1,25(OH)2D3 in adults with vitamin D insufficiency
  20. Automated antinuclear immunofluorescence antibody analysis is a reliable approach in routine clinical laboratories
  21. Infrared analyzers for breast milk analysis: fat levels can influence the accuracy of protein measurements
  22. Hematology and Coagulation
  23. A new approach to define acceptance limits for hematology in external quality assessment schemes
  24. The effects of transport by car on coagulation tests
  25. Combined measurement of factor XIII and D-dimer is helpful for differential diagnosis in patients with suspected pulmonary embolism
  26. Reference Values and Biological Variations
  27. Influence of age, gender and body mass index on late-night salivary cortisol in healthy adults
  28. Cancer Diagnostics
  29. Assessment of real-time PCR method for detection of EGFR mutation using both supernatant and cell pellet of malignant pleural effusion samples from non-small-cell lung cancer patients
  30. Detection of EGFR mutations in patients with non-small cell lung cancer by high resolution melting. Comparison with other methods
  31. Predicting outcomes of EGFR-targeted therapy in non-small cell lung cancer patients using pleural effusions samples and peptide nucleic acid probe assay
  32. Analytical and clinical performance of thyroglobulin autoantibody assays in thyroid cancer follow-up
  33. Thyroglobulin autoantibodies before radioiodine ablation predict differentiated thyroid cancer outcome
  34. Cardiovascular Diseases
  35. Real life dabigatran and metabolite concentrations, focused on inter-patient variability and assay differences in patients with atrial fibrillation
  36. Infectious Diseases
  37. HIV avidity index performance using a modified fourth-generation immunoassay to detect recent HIV infections
  38. Letters to the Editor
  39. Effect of age on serum prostate-specific antigen in women
  40. Falsely elevated thyroid-stimulating hormone value due to anti-ruthenium antibodies in a patient with primary hypothyroidism: a case report
  41. High titers of anti-infliximab antibody do not interfere with Abbott immunoassays
  42. Extraordinarily elevated serum CA19-9 in a patient with posterior mediastinum cyst: a case report
  43. Low levels of 25-OH vitamin D in women with endometriosis and associated pelvic pain
  44. Evaluation of serum cortisol biological variation in the evening withdrawal
  45. Distinction between urine crystals by automated urine analyzer SediMAX conTRUST is specific but lacks sensitivity
  46. Impact of heat-inactivation on anti-Toxoplasma IgM antibody levels
https://doi.org/10.1515/cclm-2016-1192
Keywords for this article
avidity; enzyme immunoassay; epidemiology; HIV; incidence; recent infection

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Tumor microenvironment and systemic disease: a dual target in medical oncology (also in the case of biomarkers)
  4. Reviews
  5. Sample types applied for molecular diagnosis of therapeutic management of advanced non-small cell lung cancer in the precision medicine
  6. The impact of pneumatic tube system on routine laboratory parameters: a systematic review and meta-analysis
  7. Opinion Paper
  8. How to reduce scientific irreproducibility: the 5-year reflection
  9. EFLM Paper
  10. Strategies to define performance specifications in laboratory medicine: 3 years on from the Milan Strategic Conference
  11. General Clinical Chemistry and Laboratory Medicine
  12. Intensive educational efforts combined with external quality assessment improve the preanalytical phase in general practitioner offices and nursing homes
  13. Separate patient serum sodium medians from males and females provide independent information on analytical bias
  14. Are admission procalcitonin levels universal mortality predictors across different medical emergency patient populations? Results from the multi-national, prospective, observational TRIAGE study
  15. Biochemical testing in a laboratory tent and semi-intensive care of Ebola patients on-site in a remote part of Guinea: a paradigm shift based on a bleach-sensitive point-of-care device
  16. Efficient reporting of the estimated glomerular filtration rate without height in pediatric patients with cancer
  17. Evaluation of thyroid test utilization through analysis of population-level data
  18. Relation of serum γ-glutamyl transferase activity with copper in an adult population
  19. Impact of a single oral dose of 100,000 IU vitamin D3 on profiles of serum 25(OH)D3 and its metabolites 24,25(OH)2D3, 3-epi-25(OH)D3, and 1,25(OH)2D3 in adults with vitamin D insufficiency
  20. Automated antinuclear immunofluorescence antibody analysis is a reliable approach in routine clinical laboratories
  21. Infrared analyzers for breast milk analysis: fat levels can influence the accuracy of protein measurements
  22. Hematology and Coagulation
  23. A new approach to define acceptance limits for hematology in external quality assessment schemes
  24. The effects of transport by car on coagulation tests
  25. Combined measurement of factor XIII and D-dimer is helpful for differential diagnosis in patients with suspected pulmonary embolism
  26. Reference Values and Biological Variations
  27. Influence of age, gender and body mass index on late-night salivary cortisol in healthy adults
  28. Cancer Diagnostics
  29. Assessment of real-time PCR method for detection of EGFR mutation using both supernatant and cell pellet of malignant pleural effusion samples from non-small-cell lung cancer patients
  30. Detection of EGFR mutations in patients with non-small cell lung cancer by high resolution melting. Comparison with other methods
  31. Predicting outcomes of EGFR-targeted therapy in non-small cell lung cancer patients using pleural effusions samples and peptide nucleic acid probe assay
  32. Analytical and clinical performance of thyroglobulin autoantibody assays in thyroid cancer follow-up
  33. Thyroglobulin autoantibodies before radioiodine ablation predict differentiated thyroid cancer outcome
  34. Cardiovascular Diseases
  35. Real life dabigatran and metabolite concentrations, focused on inter-patient variability and assay differences in patients with atrial fibrillation
  36. Infectious Diseases
  37. HIV avidity index performance using a modified fourth-generation immunoassay to detect recent HIV infections
  38. Letters to the Editor
  39. Effect of age on serum prostate-specific antigen in women
  40. Falsely elevated thyroid-stimulating hormone value due to anti-ruthenium antibodies in a patient with primary hypothyroidism: a case report
  41. High titers of anti-infliximab antibody do not interfere with Abbott immunoassays
  42. Extraordinarily elevated serum CA19-9 in a patient with posterior mediastinum cyst: a case report
  43. Low levels of 25-OH vitamin D in women with endometriosis and associated pelvic pain
  44. Evaluation of serum cortisol biological variation in the evening withdrawal
  45. Distinction between urine crystals by automated urine analyzer SediMAX conTRUST is specific but lacks sensitivity
  46. Impact of heat-inactivation on anti-Toxoplasma IgM antibody levels
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 19.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/cclm-2016-1192/html?lang=en
Scroll to top button