{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T04:15:36Z","timestamp":1781237736502,"version":"3.54.1"},"reference-count":41,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T00:00:00Z","timestamp":1639699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01-AI095068"],"award-info":[{"award-number":["R01-AI095068"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["UM1-AI068619"],"award-info":[{"award-number":["UM1-AI068619"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["UM1-AI068617"],"award-info":[{"award-number":["UM1-AI068617"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["UM1-AI068613"],"award-info":[{"award-number":["UM1-AI068613"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000278","name":"Department for International Development","doi-asserted-by":"publisher","award":["MR\/R010161\/1"],"award-info":[{"award-number":["MR\/R010161\/1"]}],"id":[{"id":"10.13039\/501100000278","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"name":"International Initiative for Impact Evaluation"},{"DOI":"10.13039\/100009054","name":"U.S. President\u2019s Emergency Plan for AIDS Relief","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"UK Medical Research Council","doi-asserted-by":"crossref","award":["MR\/R010161\/1"],"award-info":[{"award-number":["MR\/R010161\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Assays and multi-assay algorithms (MAAs) have been developed for population-level cross-sectional HIV incidence estimation. These algorithms use a combination of serologic and\/or non-serologic biomarkers to assess the duration of infection. We evaluated the performance of four MAAs for individual-level recency assessments.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Samples were obtained from 220 seroconverters (infected &lt;1 year) and 4,396 non-seroconverters (infected &gt;1 year) enrolled in an HIV prevention trial (HPTN 071 [PopART]); 28.6% of the seroconverters and 73.4% of the non-seroconverters had HIV viral loads \u2264400 copies\/mL. Samples were tested with two laboratory-based assays (LAg-Avidity, JHU BioRad-Avidity) and a point-of-care assay (rapid LAg). The four MAAs included different combinations of these assays and HIV viral load. Seroconverters on antiretroviral treatment (ART) were identified using a qualitative multi-drug assay.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>The MAAs identified between 54 and 100 (25% to 46%) of the seroconverters as recently-infected. The false recent rate of the MAAs for infections &gt;2 years duration ranged from 0.2%-1.3%. The MAAs classified different overlapping groups of individuals as recent vs. non-recent. Only 32 (15%) of the 220 seroconverters were classified as recent by all four MAAs. Viral suppression impacted the performance of the two LAg-based assays. LAg-Avidity assay values were also lower for seroconverters who were virally suppressed on ART compared to those with natural viral suppression.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>The four MAAs evaluated varied in sensitivity and specificity for identifying persons infected &lt;1 year as recently infected and classified different groups of seroconverters as recently infected. Sensitivity was low for all four MAAs. These performance issues should be considered if these methods are used for individual-level recency assessments.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0258644","type":"journal-article","created":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T18:42:42Z","timestamp":1639766562000},"page":"e0258644","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Evaluation of multi-assay algorithms for identifying individuals with recent HIV infection: HPTN 071 (PopART)"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7002-3676","authenticated-orcid":true,"given":"Wendy","family":"Grant-McAuley","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan","family":"Klock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Laeyendecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estelle","family":"Piwowar-Manning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Clarke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Autumn","family":"Breaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayana","family":"Moore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Ayles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry","family":"Kosloff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwame","family":"Shanaube","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Bock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nomtha","family":"Mandla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anneen","family":"van Deventer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Fidler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Donnell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Hayes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4587-791X","authenticated-orcid":true,"given":"Susan H.","family":"Eshleman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the HPTN 071 (PopART) Study Team","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,12,17]]},"reference":[{"key":"pone.0258644.ref001","unstructured":"WHO\/UNAIDS. 2011. When and how to use assays for recent infection to estimate HIV incidence at a population level. https:\/\/www.who.int\/diagnostics_laboratory\/hiv_incidence_may13_final.pdf. [Accessed October 2020]."},{"issue":"4","key":"pone.0258644.ref002","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1097\/COH.0b013e32833a0d3a","article-title":"Role of acute and early HIV infection in the sexual transmission of HIV","volume":"5","author":"WC Miller","year":"2010","journal-title":"Curr Opin HIV AIDS"},{"issue":"18","key":"pone.0258644.ref003","doi-asserted-by":"crossref","first-page":"2763","DOI":"10.1097\/QAD.0b013e32833f1142","article-title":"Beyond detuning: 10 years of progress and new challenges in the development and application of assays for HIV incidence estimation","volume":"24","author":"MP Busch","year":"2010","journal-title":"AIDS"},{"issue":"12","key":"pone.0258644.ref004","doi-asserted-by":"crossref","first-page":"e82772","DOI":"10.1371\/journal.pone.0082772","article-title":"Performance of a limiting-antigen avidity enzyme immunoassay for cross-sectional estimation of HIV incidence in the United States","volume":"8","author":"J Konikoff","year":"2013","journal-title":"PLoS One"},{"issue":"3","key":"pone.0258644.ref005","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1093\/aje\/kws436","article-title":"Estimation of HIV incidence using multiple biomarkers","volume":"177","author":"R Brookmeyer","year":"2013","journal-title":"Am J Epidemiol"},{"issue":"1","key":"pone.0258644.ref006","first-page":"1","article-title":"Estimating HIV Incidence in Populations Using Tests for Recent Infection: Issues, Challenges and the Way Forward","volume":"2","author":"TD Mastro","year":"2010","journal-title":"J HIV AIDS Surveill Epidemiol"},{"issue":"Suppl 2","key":"pone.0258644.ref007","doi-asserted-by":"crossref","first-page":"S233","DOI":"10.1097\/QAI.0b013e3182986fdf","article-title":"Cross-sectional HIV incidence estimation in HIV prevention research","volume":"63","author":"R Brookmeyer","year":"2013","journal-title":"J Acquir Immune Defic Syndr"},{"issue":"2","key":"pone.0258644.ref008","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1093\/infdis\/jis659","article-title":"HIV incidence determination in the United States: a multiassay approach","volume":"207","author":"O Laeyendecker","year":"2013","journal-title":"J Infect Dis"},{"issue":"2","key":"pone.0258644.ref009","doi-asserted-by":"crossref","DOI":"10.1002\/jia2.25082","article-title":"Identification and validation of a multi-assay algorithm for cross-sectional HIV incidence estimation in populations with subtype C infection","volume":"21","author":"O Laeyendecker","year":"2018","journal-title":"J Int AIDS Soc"},{"issue":"5","key":"pone.0258644.ref010","doi-asserted-by":"crossref","first-page":"e267","DOI":"10.1016\/S2214-109X(14)70032-4","article-title":"Effect of community-based voluntary counselling and testing on HIV incidence and social and behavioural outcomes (NIMH Project Accept; HPTN 043): a cluster-randomised trial","volume":"2","author":"TJ Coates","year":"2014","journal-title":"Lancet Glob Health"},{"issue":"2","key":"pone.0258644.ref011","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1093\/infdis\/jis658","article-title":"Use of a multifaceted approach to analyze HIV incidence in a cohort study of women in the United States: HIV Prevention Trials Network 064 Study","volume":"207","author":"SH Eshleman","year":"2013","journal-title":"J Infect Dis"},{"issue":"7","key":"pone.0258644.ref012","doi-asserted-by":"crossref","first-page":"e68349","DOI":"10.1371\/journal.pone.0068349","article-title":"Estimation of HIV incidence in a large, community-based, randomized clinical trial: NIMH project accept (HIV Prevention Trials Network 043)","volume":"8","author":"O Laeyendecker","year":"2013","journal-title":"PLoS One"},{"key":"pone.0258644.ref013","doi-asserted-by":"crossref","first-page":"37964","DOI":"10.1038\/srep37964","article-title":"Viral and Host Characteristics of Recent and Established HIV-1 Infections in Kisumu based on a Multiassay Approach","volume":"6","author":"N Otecko","year":"2016","journal-title":"Sci Rep"},{"issue":"1","key":"pone.0258644.ref014","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1186\/s12879-017-2740-y","article-title":"A comparison of self-report and antiretroviral detection to inform estimates of antiretroviral therapy coverage, viral load suppression and HIV incidence in Kwazulu-Natal, South Africa","volume":"17","author":"H Huerga","year":"2017","journal-title":"BMC Infect Dis"},{"issue":"10","key":"pone.0258644.ref015","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1089\/aid.2018.0284","article-title":"Field Validation of Limiting-Antigen Avidity Enzyme Immunoassay to Estimate HIV-1 Incidence in Cross-Sectional Survey in Swaziland","volume":"35","author":"YT Duong","year":"2019","journal-title":"AIDS Res Hum Retroviruses"},{"issue":"1","key":"pone.0258644.ref016","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1186\/s12913-021-06619-6","article-title":"Experiences and lessons learned from the real-world implementation of an HIV recent infection testing algorithm in three routine service-delivery settings in Kenya and Zimbabwe","volume":"21","author":"MM de Wit","year":"2021","journal-title":"BMC Health Serv Res"},{"issue":"3","key":"pone.0258644.ref017","doi-asserted-by":"crossref","first-page":"227","DOI":"10.4103\/ijmr.IJMR_2007_18","article-title":"Immunological markers for identifying recent HIV infection in North-West India","volume":"152","author":"CK Chauhan","year":"2020","journal-title":"Indian J Med Res"},{"key":"pone.0258644.ref018","doi-asserted-by":"crossref","first-page":"82","DOI":"10.11606\/s1518-8787.2020054002179","article-title":"Recent HIV Infection among men who have sex with men and transgender women in Tijuana","volume":"54","author":"B Skaathun","year":"2020","journal-title":"Rev Saude Publica"},{"issue":"4","key":"pone.0258644.ref019","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1111\/biom.12217","article-title":"A serial risk score approach to disease classification that accounts for accuracy and cost","volume":"70","author":"D Huynh","year":"2014","journal-title":"Biometrics"},{"issue":"2","key":"pone.0258644.ref020","doi-asserted-by":"crossref","first-page":"e0114947","DOI":"10.1371\/journal.pone.0114947","article-title":"Recalibration of the limiting antigen avidity EIA to determine mean duration of recent infection in divergent HIV-1 subtypes","volume":"10","author":"YT Duong","year":"2015","journal-title":"PLoS One"},{"issue":"1","key":"pone.0258644.ref021","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1089\/aid.2009.0133","article-title":"Development of two avidity-based assays to detect recent HIV type 1 seroconversion using a multisubtype gp41 recombinant protein","volume":"26","author":"X Wei","year":"2010","journal-title":"AIDS Res Hum Retroviruses"},{"key":"pone.0258644.ref022","unstructured":"Sedia HIV-1 LAg-Avidity EIA [package insert]. Portland, OR: Sedia Biosciences Corporation; 2018."},{"key":"pone.0258644.ref023","unstructured":"Asante HIV-1 Rapid Recency Assay [package insert]. Portland, OR: Sedia Biosciences Corporation, 2019."},{"key":"pone.0258644.ref024","unstructured":"WHO\/UNAIDS. 2014. Annual meeting of the technical working group on HIV incidence assays. https:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/162156\/WHO_HIV_2015.11_eng.pdf;sequence=1. [Accessed September 2021]."},{"issue":"7","key":"pone.0258644.ref025","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1089\/aid.2019.0286","article-title":"Impact of Early Antiretroviral Treatment Initiation on Performance of Cross-Sectional Incidence Assays","volume":"36","author":"E Klock","year":"2020","journal-title":"AIDS Res Hum Retroviruses"},{"key":"pone.0258644.ref026","unstructured":"Guideline on When to Start Antiretroviral Therapy and on Pre-Exposure Prophylaxis for HIV. WHO Guidelines Approved by the Guidelines Review Committee. Geneva. 2015."},{"issue":"2","key":"pone.0258644.ref027","doi-asserted-by":"crossref","first-page":"e55525","DOI":"10.1371\/journal.pone.0055525","article-title":"Effect of natural and ARV-induced viral suppression and viral breakthrough on anti-HIV antibody proportion and avidity in patients with HIV-1 subtype B infection","volume":"8","author":"SK Wendel","year":"2013","journal-title":"PLoS One"},{"issue":"8","key":"pone.0258644.ref028","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1089\/aid.2011.0258","article-title":"Factors associated with incorrect identification of recent HIV infection using the BED capture immunoassay","volume":"28","author":"O Laeyendecker","year":"2012","journal-title":"AIDS Res Hum Retroviruses"},{"issue":"8","key":"pone.0258644.ref029","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1097\/QAD.0000000000000221","article-title":"Incorrect identification of recent HIV infection in adults in the United States using a limiting-antigen avidity assay","volume":"28","author":"AF Longosz","year":"2014","journal-title":"AIDS"},{"issue":"4","key":"pone.0258644.ref030","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1089\/aid.2016.0105","article-title":"Short Communication: The Impact of Viral Suppression and Viral Breakthrough on Limited-Antigen Avidity Assay Results in Individuals with Clade B HIV Infection","volume":"33","author":"SK Wendel","year":"2017","journal-title":"AIDS Res Hum Retroviruses"},{"key":"pone.0258644.ref031","unstructured":"Chen A, Kammers K, Monaco D, Hudelson S, Grant-McAuley W, Moore R, et al. Antibody profiling identifies antibody targets associated with natural HIV control. [CROI 2021 Abstract 1171]."},{"issue":"3","key":"pone.0258644.ref032","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1056\/NEJMoa1814556","article-title":"Effect of Universal Testing and Treatment on HIV Incidence\u2014HPTN 071 (PopART)","volume":"381","author":"RJ Hayes","year":"2019","journal-title":"N Engl J Med"},{"issue":"1","key":"pone.0258644.ref033","first-page":"483","article-title":"Evaluation of Cross-Sectional HIV Incidence Testing in the HPTN 071 (PopART) Trial [CROI Abstract 976]. In Special Issue: Abstracts From the 2020 Conference on Retroviruses and Opportunistic Infections","volume":"28","author":"EB Klock","year":"2020","journal-title":"Top Antivir Med"},{"issue":"2","key":"pone.0258644.ref034","doi-asserted-by":"crossref","first-page":"e25452","DOI":"10.1002\/jia2.25452","article-title":"Determination of HIV status and identification of incident HIV infections in a large, community-randomized trial: HPTN 071 (PopART)","volume":"23","author":"SH Eshleman","year":"2020","journal-title":"J Int AIDS Soc"},{"issue":"10","key":"pone.0258644.ref035","doi-asserted-by":"crossref","first-page":"e25899","DOI":"10.1371\/journal.pone.0025899","article-title":"The effect of sample handling on cross sectional HIV incidence testing results","volume":"6","author":"O Laeyendecker","year":"2011","journal-title":"PLoS One"},{"key":"pone.0258644.ref036","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.cca.2014.03.016","article-title":"The development and validation of a method using high-resolution mass spectrometry (HRMS) for the qualitative detection of antiretroviral agents in human blood","volume":"433","author":"MA Marzinke","year":"2014","journal-title":"Clin Chim Acta"},{"issue":"16","key":"pone.0258644.ref037","doi-asserted-by":"crossref","first-page":"2439","DOI":"10.1097\/QAD.0000000000000429","article-title":"Independent assessment of candidate HIV incidence assays on specimens in the CEPHIA repository","volume":"28","author":"R Kassanjee","year":"2014","journal-title":"AIDS"},{"key":"pone.0258644.ref038","volume-title":"R: A language and environment for statistical computing","author":"R Core Team","year":"2013"},{"key":"pone.0258644.ref039","volume-title":"Modern Applied Statistics with S","author":"WNVaBD Ripley","year":"2002","edition":"4"},{"key":"pone.0258644.ref040","unstructured":"Virasakdi Chongsuvivatwong (2018). epiDisplay: Epidemiological Data Display Package. R package version 3.5.0.1; 2018 [Accessed August, 2020]. https:\/\/CRAN.R-project.org\/package=epiDisplay."},{"key":"pone.0258644.ref041","unstructured":"Grebe E, Facente SN, Hampton D, Cheng C, Owen R, Keating SM, et al. Asant\u00e9\u2122 HIV-1 Rapid Recency\u00ae Assay Evaluation Report (Version 1.0). Zenodo; 2019."}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0258644","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T18:43:33Z","timestamp":1639766613000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0258644"}},"subtitle":[],"editor":[{"given":"Orna","family":"Mor","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,12,17]]},"references-count":41,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12,17]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0258644","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,17]]}}}