Discrimination between recent and non-recent HIV infections using routine diagnostic serological assays

Hassan, Jaythoon; Moran, Joanne; Murphy, Gary; Mason, Olivia; Connell, Jeff; Gascun, Cillian De

doi:10.1007/s00430-019-00590-0

Cited by 14 publications

(12 citation statements)

References 19 publications

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“…The Architect avidity has been described as an assay with a relative high sensitivity and specificity compared to some other incidence assays; it correctly classified recent HIV in 70% of cases and correctly classified established HIV infection in 95% of cases in a validation study by Hassan et al ( 34 ). We compared the performance of RITA with routinely collected data of last HIV negative test results.…”

Section: Discussionmentioning

confidence: 99%

Monitoring Recently Acquired HIV Infections in Amsterdam, The Netherlands: The Attribution of Test Locations

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Baan

Sighem

et al. 2021

Front. Reprod. Health

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Background: Surveillance of recent HIV infections (RHI) using an avidity assay has been implemented at Dutch sexual health centres (SHC) since 2014, but data on RHI diagnosed at other test locations is lacking.Setting: Implementation of the avidity assay in HIV treatment clinics for the purpose of studying RHI among HIV patients tested at different test locations.Methods: We retrospectively tested leftover specimens from newly diagnosed HIV patients in care in 2013–2015 in Amsterdam. Avidity Index (AI) values ≤0.80 indicated recent infection (acquired ≤6 months prior to diagnosis), and AI > 0.80 indicated established infection (acquired >6 months prior to diagnosis). An algorithm for RHI was applied to correct for false recency. Recency based on this algorithm was compared with recency based on epidemiological data only. Multivariable logistic regression analysis was used to identify factors associated with RHI among men who have sex with men (MSM).Results: We tested 447 specimens with avidity; 72% from MSM. Proportions of RHI were 20% among MSM and 10% among heterosexuals. SHC showed highest proportions of RHI (27%), followed by GPs (15%), hospitals (5%), and other/unknown locations (11%) (p < 0.001). Test location was the only factor associated with RHI among MSM. A higher proportion of RHI was found based on epidemiological data compared to avidity testing combined with the RHI algorithm.Conclusion: SHC identify more RHI infections compared to other test locations, as they serve high-risk populations and offer frequent HIV testing. Using avidity-testing for surveillance purposes may help targeting prevention programs, but the assay lacks robustness and its added value may decline with improved, repeat HIV testing and data collection.

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Section: Discussionmentioning

confidence: 99%

Monitoring Recently Acquired HIV Infections in Amsterdam, The Netherlands: The Attribution of Test Locations

Slurink¹,

Baan

Sighem

et al. 2021

Front. Reprod. Health

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“…There have been 21 separate large-scale research projects funded by NIH, the Bill and Melinda Gates Foundation, and others, using CEPHIA specimens as a foundation for investigation of assays in various HIV incidence and diagnostic applications. Eleven scientific articles 2, 11, 26, 27, 43, 45, 47– 51 highlighting important findings about the use (and misuse) of HIV incidence assays have been published to date with CEPHIA authorship, as a direct result of CEPHIA specimens being made available to researchers upon request.…”

Section: Review and Findingsmentioning

confidence: 99%

Challenges to the performance of current HIV diagnostic assays and the need for centralized specimen archives: a review of the Consortium for the Evaluation and Performance of HIV Incidence Assays (CEPHIA) repository

et al. 2019

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Background: New challenges for diagnosis of HIV infection abound, including the impact on key viral and immunological markers of HIV vaccine studies, pre-exposure prophylaxis usage and breakthrough infections, and very early initiation of anti-retroviral treatment. These challenges impact the performance of current diagnostic assays, and require suitable specimens for development and evaluation. In this article we review and describe an archive developed by the Consortium for the Evaluation and Performance of HIV Incidence Assays (CEPHIA), in order to identify the critical features required to create a centralized specimen archive to support these current and future developments. Review and Findings: We review and describe the CEPHIA repository, a large, consolidated repository comprised of over 31,000 highly-selected plasma samples and other body fluid specimen types, with over 50 purposely designed specimen panels distributed to 19 groups since 2012. The CEPHIA repository provided financial return on investment, supported the standardization of HIV incidence assays, and informed guidance and standards set by the World Health Organization and UNAIDS. Unified data from extensively characterized specimens has allowed this resource to support biomarker discovery, assay optimization, and development of new strategies for estimating duration of HIV infection. Critical features of a high-value repository include 1) extensively-characterized samples, 2) high-quality clinical background data, 3) multiple collaborations facilitating ongoing sample replenishment, and 4) sustained history of high-level specimen utilization. Conclusion: With strong governance and leadership, a large consolidated archive of samples from multiple studies provides investigators and assay developers with easy access to diverse samples designed to address challenges associated with HIV diagnosis, helping to enable improvements to HIV diagnostic assays and ultimately elimination of HIV. Its creation and ongoing utilization should compel funders, institutions and researchers to address and improve upon current approaches to sharing specimens.

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“…Numerous HIV infection biomarkers of this kind have been identified [1][2][3][4] though they are almost exclusively used for surveillance purposes. Despite their increasing use in clinical diagnosis [5], the use of infection-dating markers in individuals remains somewhat controversial-in part because of the lack of a systematic framework for the interpretation of such data.…”

Section: Introductionmentioning

confidence: 99%

Quantitative interpretation of Sedia LAg Assay test results after HIV diagnosis

2022

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Background Testing for ‘recent HIV infection’ is common in surveillance, where only population-level estimates (of incidence) are reported. Typically, ‘recent infection’ is a category, 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. Methods 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. Results 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. Conclusion 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.

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Discrimination between recent and non-recent HIV infections using routine diagnostic serological assays

Cited by 14 publications

References 19 publications

Monitoring Recently Acquired HIV Infections in Amsterdam, The Netherlands: The Attribution of Test Locations

Monitoring Recently Acquired HIV Infections in Amsterdam, The Netherlands: The Attribution of Test Locations

Challenges to the performance of current HIV diagnostic assays and the need for centralized specimen archives: a review of the Consortium for the Evaluation and Performance of HIV Incidence Assays (CEPHIA) repository

Quantitative interpretation of Sedia LAg Assay test results after HIV diagnosis

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