Computational analysis of antibody dynamics identifies recent HIV-1 infection.
Abstract
Accurate HIV-1 incidence estimation is critical to the success of HIV-1 prevention
strategies. Current assays are limited by high false recent rates (FRRs) in certain
populations and a short mean duration of recent infection (MDRI). Dynamic early HIV-1
antibody response kinetics were harnessed to identify biomarkers for improved incidence
assays. We conducted retrospective analyses on circulating antibodies from known recent
and longstanding infections and evaluated binding and avidity measurements of Env
and non-Env antigens and multiple antibody forms (i.e., IgG, IgA, IgG3, IgG4, dIgA,
and IgM) in a diverse panel of 164 HIV-1-infected participants (clades A, B, C). Discriminant
function analysis identified an optimal set of measurements that were subsequently
evaluated in a 324-specimen blinded biomarker validation panel. These biomarkers included
clade C gp140 IgG3, transmitted/founder clade C gp140 IgG4 avidity, clade B gp140
IgG4 avidity, and gp41 immunodominant region IgG avidity. MDRI was estimated at 215
day or alternatively, 267 days. FRRs in untreated and treated subjects were 5.0% and
3.6%, respectively. Thus, computational analysis of dynamic HIV-1 antibody isotype
and antigen interactions during infection enabled design of a promising HIV-1 recency
assay for improved cross-sectional incidence estimation.
Type
Journal articleSubject
CEPHIA groupHumans
HIV-1
HIV Infections
Immunoglobulin G
HIV Antibodies
HIV Antigens
Incidence
Retrospective Studies
Computational Biology
Antigen-Antibody Reactions
Antibody Affinity
Time Factors
Biomarkers
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https://hdl.handle.net/10161/22001Published Version (Please cite this version)
10.1172/jci.insight.94355Publication Info
(2017). Computational analysis of antibody dynamics identifies recent HIV-1 infection. JCI insight, 2(24). 10.1172/jci.insight.94355. Retrieved from https://hdl.handle.net/10161/22001.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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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
Barton Ford Haynes
Frederic M. Hanes Distinguished Professor of Medicine
Barton F. Haynes, M.D. is the Frederic M. Hanes Professor of Medicine and Immunology,
and Director of the Duke Human Vaccine Institute. Prior to leading the DHVI, Dr. Haynes
served as Chief of the Division of Rheumatology, Allergy and Clinical Immunology,
and later as Chair of the Department of Medicine. As Director of the Duke Human Vaccine
Institute, Bart Haynes is leading a team of investigators working on vaccines for
emerging infections, including tuberculosis, pandemic influenza, emergi
Hua-Xin Liao
Adjunct Professor in the Department of Medicine
Dr. Liao is a Professor of Medicine and Research Director of Duke Human Vaccine Institute.
Dr. Liao is a MD virologistt rained in China. In early 1980’s, Dr. Liao made
major contributions to the first isolation of epidemic hemorrhagic fever virus (hataanvirus)
from Apodemus agraius using tissue culture in China. The successful identification
and isolation of Hataanvirus enabled the early diagnosis and treatment of the disease,
and advancement of HFRS research towards prevention by de
This author no longer has a Scholars@Duke profile, so the information shown here reflects
their Duke status at the time this item was deposited.
Xiaoying Shen
Associate Professor in Surgery
Dr. Shen is an Associate Director and Deputy of the Laboratory for HIV and COVID-19
Vaccine Research & Development in the Department of Surgery, Division of Surgical
Sciences at Duke University Medical Center. Her research interest focuses on the humoral
immune response following virus infection or vaccination. During the past decade,
she has worked intensively on the specificity and breadth of binding antibody responses
against HIV. Dr. Shen’s team developed assays and
Georgia Doris Tomaras
Professor in Surgery
Dr. Georgia Tomaras is a tenured Professor of Surgery, Professor of Immunology, Professor
of Molecular Genetics and Microbiology and is a Fellow of the American Academy of
Microbiology (AAM) and a Fellow of the American Association for the Advancement of
Science (AAAS). Dr. Tomaras is Co-Director of the Center for Human Systems Immunology
(CHSI) Duke University and Director of the Duke Center for AIDS Research (CFAR). Her
national and international leadership roles i
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