Comparison of Detection Limits of Fourth- and Fifth-Generation Combination HIV Antigen-Antibody, p24 Antigen, and Viral Load Assays on Diverse HIV Isolates.
Abstract
Detection of acute HIV infection is critical for HIV public health and diagnostics.
Clinical fourth-generation antigen (Ag)/antibody (Ab) combination (combo) and p24
Ag immunoassays have enhanced detection of acute infection compared to Ab-alone assays
but require ongoing evaluation with currently circulating diverse subtypes. Genetically
and geographically diverse HIV clinical isolates were used to assess clinical HIV
diagnostic, blood screening, and next-generation assays. Three-hundred-member panels
of 20 serially diluted well-characterized antibody-negative HIV isolates for which
the researchers were blind to the results (blind panels) were distributed to manufacturers
and end-user labs to assess the relative analytic sensitivity of currently approved
and preapproved clinical HIV fourth-generation Ag/Ab combo or p24 Ag-alone immunoassays
for the detection of diverse subtypes. The limits of detection (LODs) of virus were
estimated for different subtypes relative to confirmed viral loads. Analysis of immunoassay
sensitivity was benchmarked against confirmed viral load measurements on the blind
panel. On the basis of the proportion of positive results on 300 observations, all
Ag/Ab combo and standard sensitivity p24 Ag assays performed similarly and within
half-log LODs, illustrating the similar breadth of reactivity and diagnostic utility.
Ultrasensitive p24 Ag assays achieved dramatically increased sensitivities, while
the rapid combo assays performed poorly. The similar performance of the different
commercially available fourth-generation assays on diverse subtypes supports their
use in broad geographic settings with locally circulating HIV clades and recombinant
strains. Next-generation preclinical ultrasensitive p24 Ag assays achieved dramatically
improved sensitivity, while rapid fourth-generation assays performed poorly for p24
Ag detection.
Type
Journal articleSubject
HumansHIV
HIV Infections
HIV Core Protein p24
HIV Antibodies
HIV Antigens
Immunoassay
AIDS Serodiagnosis
Viral Load
Sensitivity and Specificity
Benchmarking
Limit of Detection
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https://hdl.handle.net/10161/21999Published Version (Please cite this version)
10.1128/jcm.02045-17Publication Info
Stone, Mars; Bainbridge, John; Sanchez, Ana M; Keating, Sheila M; Pappas, Andrea;
Rountree, Wes; ... Busch, Michael P (2018). Comparison of Detection Limits of Fourth- and Fifth-Generation Combination HIV Antigen-Antibody,
p24 Antigen, and Viral Load Assays on Diverse HIV Isolates. Journal of clinical microbiology, 56(8). 10.1128/jcm.02045-17. Retrieved from https://hdl.handle.net/10161/21999.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Thomas Norton Denny
Professor in Medicine
Thomas N. Denny, MSc, M.Phil, is the Chief Operating Officer of the Duke Human Vaccine
Institute (DHVI), Associate Dean for Duke Research and Discovery @RTP, and a Professor
of Medicine in the Department of Medicine at Duke University Medical Center. He is
also an Affiliate Member of the Duke Global Health Institute. Previously, he served
on the Health Sector Advisory Council of the Duke University Fuquay School of Business.
Prior to joining Duke, he was an Associate Professor of Pathology, Labo

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