{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T17:45:17Z","timestamp":1772214317616,"version":"3.50.1"},"reference-count":16,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T00:00:00Z","timestamp":1658966400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"DST-NRF Centre of Excellence in Epidemiological Modelling and Analysis (SACEMA), Stellenbosch University, Stellenbosch, South Africa"},{"name":"University of the Free State, Bloemfontein, South Africa"}],"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>\n                      Testing for \u2018recent HIV infection\u2019 is common in surveillance, where only population-level estimates (of incidence) are reported. Typically, \u2018recent infection\u2019 is a\n                      <jats:italic>category<\/jats:italic>\n                      , obtained by applying a threshold on an underlying continuous biomarker from some laboratory assay(s). Interpreting the biomarker values obtained for individual subjects, as estimates of the date of infection, has obvious potential applications in the context of studies of early infection, and has also for some years attracted significant interest as an extra component of post-test counselling and treatment initiation. The applicable analyses have typically run aground on the complexity of the full biomarker growth model, which is in principle a non-linear mixed-effects model of unknown structure, the fitting of which seems infeasible from realistically obtainable data.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>It is known that to estimate Mean Duration of Recent Infection (MDRI) at a given value of the recent\/non-recent -infection discrimination threshold, one may compress the full biomarker growth model into a relation capturing the probability of a recent test result as a function of time t since infection, given a value of assay threshold h which defines the recent\/non-recent discrimination. We demonstrate that the derivative (gradient), with respect to h. of the probability of recent infection, seen as a function of both t and h, is identical to the formal likelihood relevant to Bayesian inference of the time since seroconversion, for a subject yielding an assay result h, at or close to the date of their first positive HIV test. This observation bypasses the need for fitting a complex detailed biomarker growth model. Using publicly available data from the CEPHIA collaboration, we calibrated this likelihood function for the Sedia Lag assay, and performed Bayesian inference on hypothetical infection data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We demonstrate the generation of posteriors for infection date, for patients with various delays between their last negative and first positive HIV test, and a range of LAg assay results (ODn) hypothetically obtained on the date of the first positive result.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Depending on the last-negative \/ first-positive interval, there is a range of ODn values that yields posteriors significantly different from the uniform prior one would be left with based merely on interval censoring. Hence, a LAg ODn obtained on the date of, or soon after, diagnosis contains potentially significant information about infection dating. It seems worth analysing other assays with meaningful dynamic range, especially tests already routinely used in primary HIV diagnosis (for example chemiluminescent assays and reader\/cartridge lateral flow tests which admit objective variable line intensity readings) which have a sufficient dynamic range that corresponds to a clinically meaningful range of times-since-infection that are worth distinguishing from each other.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0271763","type":"journal-article","created":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T13:53:59Z","timestamp":1659016439000},"page":"e0271763","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Quantitative interpretation of Sedia LAg Assay test results after HIV diagnosis"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1062-0417","authenticated-orcid":true,"given":"Joseph B.","family":"Sempa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7046-7245","authenticated-orcid":true,"given":"Eduard","family":"Grebe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7139-7509","authenticated-orcid":true,"given":"Alex","family":"Welte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,7,28]]},"reference":[{"key":"pone.0271763.ref001","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.0271763.ref002","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1097\/QAD.0000000000001209","article-title":"Viral load criteria and threshold optimization to improve HIV incidence assay characteristics","volume":"30","author":"R Kassanjee","year":"2016","journal-title":"Aids"},{"key":"pone.0271763.ref003","doi-asserted-by":"crossref","first-page":"e0220345","DOI":"10.1371\/journal.pone.0220345","article-title":"Performance comparison of the Maxim and Sedia Limiting Antigen Avidity assays for HIV incidence surveillance.","volume":"14","author":"JB Sempa","year":"2019","journal-title":"PLoS One."},{"key":"pone.0271763.ref004","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1097\/QAI.0000000000001146","article-title":"Performance of the Bio-Rad Geenius HIV1\/2 Supplemental Assay in Detecting \u201cRecent\u201d HIV Infection and Calculating Population Incidence.","volume":"73","author":"SM Keating","year":"2016","journal-title":"J Acquir Immune Defic Syndr."},{"key":"pone.0271763.ref005","first-page":"0","article-title":"Discrimination between recent and non-recent HIV infections using routine diagnostic serological assays","volume":"0","author":"J Hassan","year":"2019","journal-title":"Med Microbiol Immunol"},{"key":"pone.0271763.ref006","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1097\/00002030-200309050-00005","article-title":"Dynamics of HIV viremia and antibody seroconversion in plasma donors: implications for diagnosis and staging of primary HIV infection","volume":"17","author":"EW Fiebig","year":"2003","journal-title":"AIDS"},{"key":"pone.0271763.ref007","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1186\/s12879-019-4543-9","article-title":"Interpreting HIV diagnostic histories into infection time estimates: analytical framework and online tool.","volume":"19","author":"E Grebe","year":"2019","journal-title":"BMC Infect Dis"},{"key":"pone.0271763.ref008","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/1742-4690-10-56","article-title":"A novel acute HIV infection staging system based on 4th generation immunoassay.","volume":"10","author":"J Ananworanich","year":"2013","journal-title":"Retrovirology"},{"key":"pone.0271763.ref009","doi-asserted-by":"crossref","first-page":"e136","DOI":"10.1017\/S0950268819000244","article-title":"Integration of a recent infection testing algorithm into HIV surveillance in Ireland: improving HIV knowledge to target prevention","volume":"147","author":"E Robinson","year":"2019","journal-title":"Epidemiol Infect"},{"issue":"Suppl 3","key":"pone.0271763.ref010","doi-asserted-by":"crossref","first-page":"e25513","DOI":"10.1002\/jia2.25513","article-title":"Can HIV recent infection surveillance help us better understand where primary prevention efforts should be targeted? Results of three pilots integrating a recent infection testing algorithm into routine programme activities in Kenya and Zimbabwe","volume":"23","author":"BD Rice","year":"2020","journal-title":"J Int AIDS Soc"},{"key":"pone.0271763.ref011","doi-asserted-by":"crossref","first-page":"e53","DOI":"10.1017\/S0950268820000503","article-title":"Estimated dates of detectable infection (EDDIs) as an improvement upon Fiebig staging for HIV infection dating.","volume":"148","author":"SN Facente","year":"2020","journal-title":"Epidemiol Infect"},{"key":"pone.0271763.ref012","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1017\/S0950268816002910","article-title":"Moving towards a reliable HIV incidence test\u2013current status, resources available, future directions and challenges ahead","volume":"145","author":"G MURPHY","year":"2017","journal-title":"Epidemiol Infect"},{"key":"pone.0271763.ref013","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1097\/EDE.0b013e3182576c07","article-title":"A new general biomarker-based incidence estimator.","volume":"23","author":"R Kassanjee","year":"2012","journal-title":"Epidemiology"},{"key":"pone.0271763.ref014","unstructured":"Sedia Biosciences Corporation. SediaTM HIV-1 LAg-Avidity EIA: single well avidity enzyme immunoassay for detection of recent HIV-1 infection, Cat. No. 1002. 2016. Available: http:\/\/www.sediabio.com\/LiteratureRetrieve.aspx?ID=134692."},{"key":"pone.0271763.ref015","article-title":"Cross-Sectional HIV Incidence Surveillance: A Benchmarking of Approaches for Estimating the \u201cMean Duration of Recent Infection\u201d.","volume":"9","author":"R Kassanjee","year":"2017","journal-title":"Stat Commun Infect Dis"},{"key":"pone.0271763.ref016","unstructured":"The Foundation for AIDS Research. New HIV Testing Strategies in PEPFAR COP19: Rollout and Human Rights Concerns. Washington DC.; 2019. Available: https:\/\/www.amfar.org\/uploadedFiles\/_amfarorg\/Articles\/On_The_Hill\/2019\/COP19.pdf."}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0271763","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,24]],"date-time":"2023-11-24T21:48:47Z","timestamp":1700862527000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0271763"}},"subtitle":[],"editor":[{"given":"In\u00e9s P.","family":"Mari\u00f1o","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2022,7,28]]},"references-count":16,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,7,28]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0271763","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.09.13.21263495","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,28]]}}}