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      Evaluation of the Abbott ARCHITECT HIV Ag/Ab combo assay for determining recent HIV-1 infection

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          Abstract

          Background

          Given the challenges and costs associated with implementing HIV-1 incidence assay testing, there is great interest in evaluating the use of commercial HIV diagnostic tests for determining recent HIV infection. A diagnostic test with the capability of providing reliable data for the determination of recent HIV infection without substantial modifications to the test protocol would have a significant impact on HIV surveillance. The Abbott ARCHITECT HIV Ag/Ab Combo Assay is an antigen/antibody immunoassay, which meets the criteria as the first screening test in the recommended HIV laboratory diagnostic algorithm for the United States.

          Methods

          In this study, we evaluated the performance characteristics of the ARCHITECT HIV Ag/Ab Combo signal-to-cutoff ratio (S/Co) for determining recent infection, including estimation of the mean duration of recent infection (MDRI) and false recent rate (FRR), and selection of recency cutoffs.

          Results

          The MDRI estimates for the S/Co recency cutoff of 400 is within the 4 to 12 months range recommended for HIV incidence assays, and the FRR rate for this cutoff was 1.5%. Additionally, ARCHITECT Combo S/Co values were compared relative to diagnostic test results from two prior prospective HIV-1 diagnostic studies in order to validate the use of the S/Co for both diagnostic and recency determination.

          Conclusion

          Dual-use of the ARCHITECT Combo assay data for diagnostic and incidence purposes would reduce the need for separate HIV incidence testing and allow for monitoring of recent infection for incidence estimation and other public health applications.

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          Most cited references30

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          The Women's Interagency HIV Study: an observational cohort brings clinical sciences to the bench.

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            The Women's Interagency HIV Study. WIHS Collaborative Study Group.

            The Women's Interagency HIV Study comprises the largest U.S. cohort to date of human immunodeficiency virus (HIV)-seropositive women (N = 2,058) with a comparison cohort of seronegative women (N = 568). The methodology, training, and quality assurance activities employed are described. The study population, enrolled between October 1994 and November 1995 through six clinical consortia throughout the United States (totaling 23 sites) represents a typically hard-to-reach study population. More than half of the women in each cohort were living below the federally defined levels of poverty. The women ranged in age from 16 to 73 years; approximately one-quarter self-identified as Latina or Hispanic, over one-half as African-American not of Hispanic origin, and less than 20% as white, non-Hispanic origin. Self-reporting of HIV exposure risk included injection drug use by 34% of the seropositive women and 28% of the seronegative women, heterosexual contact (42% vs 26%), transfusion risk (4% vs 3%) and no identified risk (20% vs 43%). Demographic and HIV exposure risk characteristics of the seropositive cohort were comparable with characteristics of nationally reported AIDS cases in U.S. women. This well characterized cohort of HIV-seropositive and high-risk seronegative women represents a rich opportunity for future studies of HIV disease progression and pathogenesis.
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              Independent assessment of candidate HIV incidence assays on specimens in the CEPHIA repository

              Objective: Cross-sectional HIV incidence surveillance, using assays that distinguish ‘recent’ from ‘nonrecent’ infections, has been hampered by inadequate performance and characterization of incidence assays. In this study, the Consortium for the Evaluation and Performance of HIV Incidence Assays presents results of the first independent evaluation of five incidence assays (BED, Limiting Antigen Avidity, Less-sensitive Vitros, Vitros Avidity and BioRad Avidity). Design: A large repository of diverse specimens from HIV-positive patients was established, multiple assays were run on 2500 selected specimens, and data were analyzed to estimate assay characteristics relevant for incidence surveillance. Methods: The mean duration of recent infection (MDRI, average time ‘recent’ while infected for less than some time cut-off T) was estimated from longitudinal data on seroconverters by regression. The false-recent rate (FRR, probability of testing ‘recent’ when infected for longer than T) was explored by measuring the proportions of ‘recent’ results in various subsets of patients. Results: Assays continue to fail to attain the simultaneously large MDRI and small FRR demanded by existing performance guidelines. All assays produce high FRRs amongst virally suppressed patients (>40%), including elite controllers and treated patients. Conclusions: Results from this first independent evaluation provide valuable information about the current performance of assays, and suggest the need for further optimization. Variation of ‘recent’/‘nonrecent’ thresholds and the use of multiple antibody-maturation assays, as well as other biomarkers, can now be explored, using the rich data generated by the Consortium for the Evaluation and Performance of HIV Incidence Assays. Consistently high FRRs amongst those virally suppressed suggest that viral load will be a particularly valuable supplementary marker. Video abstract:
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: Project administrationRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Methodology
                Role: Formal analysisRole: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: ConceptualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                1 July 2021
                2021
                : 16
                : 7
                : e0242641
                Affiliations
                [1 ] Division of HIV/ AIDS Prevention, National Center for HIV/AIDS, Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
                [2 ] Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, United States of America
                [3 ] Downstate Medical Center, State University of New York, Brooklyn, New York, United States of America
                [4 ] Department of Medicine / Division of Infectious Diseases, Georgetown University, Washington, DC, United States of America
                [5 ] California State Department of Health, Berkeley, California, United States of America
                [6 ] Department of Medicine, Stroger Hospital of Cook County, Chicago, Illinois, United States of America
                [7 ] Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America
                [8 ] Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
                [9 ] Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, United States of America
                [10 ] Division of Infectious Diseases, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, United States of America
                [11 ] School of Nursing, Public Health and Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America
                Asociacion Civil Impacta Salud y Educacion, PERU
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0002-1785-6548
                Article
                PONE-D-20-34878
                10.1371/journal.pone.0242641
                8248699
                34197451
                0ff33fd9-ec7c-4a16-8d59-680dcf041a1b

                This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

                History
                : 5 November 2020
                : 2 June 2021
                Page count
                Figures: 2, Tables: 3, Pages: 11
                Funding
                Funded by: intramural CDC funding
                Award Recipient :
                This work was supported through intramural CDC funding.
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