Antiviral inhibitory capacity of CD8+ T cells predicts the rate of CD4+ T-cell decline in HIV-1 infection.
Date
2012-08-15
Journal Title
Journal ISSN
Volume Title
Repository Usage Stats
views
downloads
Citation Stats
Attention Stats
Abstract
BACKGROUND: Rare human immunodeficiency virus type 1 (HIV-1)-infected individuals who maintain control of viremia without therapy show potent CD8+ T-cell-mediated suppression of viral replication in vitro. Whether this is a determinant of the rate of disease progression in viremic individuals is unknown. METHODS: We measured CD8+ T-cell-mediated inhibition of a heterologous HIV-1 isolate in 50 HIV-1-seropositive adults with diverse progression rates. Linear mixed models were used to determine whether CD8+ T-cell function could explain variation in the rate of CD4+ T-cell decline. RESULTS: There was a significant interaction between CD8+ T-cell antiviral activity in vitro and the rate of CD4+ T-cell decline in chronically infected individuals (P < .0001). In a second prospective analysis of recently infected subjects followed for up to 3 years, CD8+ T-cell antiviral activity strongly predicted subsequent CD4+ T-cell decline (P < .0001) and explained up to 73% of the interindividual variation in the CD4+ T-cell slope. In addition, it was inversely associated with viral load set point (r = -0.68 and P = .002). CONCLUSIONS: The antiviral inhibitory capacity of CD8+ T cells is highly predictive of CD4+ T-cell loss in early HIV-1 infection. It has potential as a benchmark of effective immunity in vaccine evaluation.
Type
Department
Description
Provenance
Subjects
Citation
Permalink
Published Version (Please cite this version)
Publication Info
Yang, H, H Wu, G Hancock, G Clutton, N Sande, X Xu, H Yan, X Huang, et al. (2012). Antiviral inhibitory capacity of CD8+ T cells predicts the rate of CD4+ T-cell decline in HIV-1 infection. J Infect Dis, 206(4). pp. 552–561. 10.1093/infdis/jis379 Retrieved from https://hdl.handle.net/10161/14731.
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.
Collections
Scholars@Duke
Thomas Norton Denny
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, Laboratory Medicine and Pediatrics, Associate Professor of Preventive Medicine and Community Health and Assistant Dean for Research in Health Policy at the New Jersey Medical School, Newark, New Jersey. He has served on numerous committees for the NIH over the last two decades and currently is the principal investigator of an NIH portfolio in excess of 65 million dollars. Mr. Denny was a 2002-2003 Robert Wood Johnson Foundation Health Policy Fellow at the Institute of Medicine of the National Academies (IOM). As a fellow, he served on the US Senate Health, Education, Labor and Pensions Committee with legislation/policy responsibilities in global AIDS, bioterrorism, clinical trials/human subject protection and vaccine related-issues.
As the Chief Operating Officer of the DHVI, Mr. Denny has senior oversight of the DHVI research portfolio and the units/teams that support the DHVI mission. He has extensive international experience and previously was a consultant to the U.S. Centers for Disease Control and Prevention (CDC) for the President’s Emergency Plan for AIDS Relief (PEPFAR) project to oversee the development of an HIV and Public Health Center of Excellence laboratory network in Guyana. In September 2004, the IOM appointed him as a consultant to their Board on Global Health Committee studying the options for overseas placement of U.S. health professionals and the development of an assessment plan for activities related to the 2003 PEPFAR legislative act. In the 1980s, Mr. Denny helped establish a small laboratory in the Republic of Kalmykia (former Soviet Union) to improve the care of children with HIV/AIDS and served as a Board Member of the Children of Chernobyl Relief Fund Foundation. In 2005, Mr. Denny was named a consulting medical/scientific officer to the WHO Global AIDS Program in Geneva. He has also served as program reviewers for the governments of the Netherlands and South Africa as well as an advisor to several U.S. biotech companies. He currently serves as the Chair of the Scientific Advisory Board for Grid Biosciences.
Mr. Denny has authored and co-authored more than 200 peer-reviewed papers and serves on the editorial board of Communications in Cytometry and Journal of Clinical Virology. He holds an M.Sc in Molecular and Biomedical Immunology from the University of East London and a degree in Medical Law (M.Phil) from the Institute of Law and Ethics in Medicine, School of Law, University of Glasgow. In 1991, he completed a course of study in Strategic Management at The Wharton School, University of Pennsylvania. In 1993, he completed the Program for Advanced Training in Biomedical Research Management at Harvard School of Public Health. In December 2005, he was inducted as a Fellow into the College of Physicians of Philadelphia, the oldest medical society in the US.
While living in New Jersey, Mr. Denny was active in his community, gaining additional experience from two publicly elected positions. In 2000, Mr. Denny was selected by the New Jersey League of Municipalities to Chair the New Jersey Community Mental Health Citizens’ Advisory Board and Mental Health Planning Council as a gubernatorial appointment.
Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.