Dynamics of Immune Reconstitution and Activation Markers in HIV plus Treatment-Naive Patients Treated with Raltegravir, Tenofovir Disoproxil Fumarate and Emtricitabine

Nicholas T. Funderburg; Adriana Andrade; Ellen S. Chan; Susan L. Rosenkranz; Darlene Lu; Brian Clagett; Heather A. Pilch-Cooper; Benigno Rodriguez; Judith Feinberg; Eric Daar; John Mellors; Daniel Kuritzkes; Jeffrey M. Jacobson; Michael M. Lederman

doi:10.1371/journal.pone.0083514

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Dynamics of Immune Reconstitution and Activation Markers in HIV plus Treatment-Naive Patients Treated with Raltegravir, Tenofovir Disoproxil Fumarate and Emtricitabine

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Dynamics of Immune Reconstitution and Activation Markers in HIV plus Treatment-Naive Patients Treated with Raltegravir, Tenofovir Disoproxil Fumarate and Emtricitabine

Nicholas T. Funderburg, Adriana Andrade, Ellen S. Chan, Susan L. Rosenkranz, Darlene Lu, Brian Clagett, Heather A. Pilch-Cooper, Benigno Rodriguez, Judith Feinberg, Eric Daar, …

PloS one, v 8(12)

18 Dec 2013

DOI: https://doi.org/10.1371/journal.pone.0083514

PMID: 24367599

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Abstract

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Background: The dynamics of CD4+ T cell reconstitution and changes in immune activation and inflammation in HIV-1 disease following initiation of antiretroviral therapy (ART) are incompletely defined and their underlying mechanisms poorly understood. Methods: Thirty-nine treatment-naive patients were treated with raltegravir, tenofovir DF and emtricitabine. Immunologic and inflammatory indices were examined in persons with sustained virologic control during 48 weeks of therapy. Results: Initiation of ART increased CD4+ T cell numbers and decreased activation and cell cycle entry among CD4+ and CD8+ T cell subsets, and attenuated markers of coagulation (D-dimer levels) and inflammation (IL-6 and TNFr1). These indices decayed at different rates and almost all remained elevated above levels measured in HIV-seronegatives through 48 weeks of viral control. Greater first and second phase CD4+ T cell restoration was related to lower T cell activation and cell cycling at baseline, to their decay with treatment, and to baseline levels of selected inflammatory indices, but less so to their changes on therapy. Conclusions: ART initiation results in dynamic changes in viral replication, T cell restoration, and indices of immune activation, inflammation, and coagulation. These findings suggest that determinants of T cell activation/cycling and inflammation/coagulation may have distinguishable impact on immune homeostasis.

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Title: Dynamics of Immune Reconstitution and Activation Markers in HIV plus Treatment-Naive Patients Treated with Raltegravir, Tenofovir Disoproxil Fumarate and Emtricitabine
Creators: Nicholas T. Funderburg - Case Western Reserve University
Adriana Andrade - Johns Hopkins University
Ellen S. Chan - Harvard University
Susan L. Rosenkranz - Harvard University
Darlene Lu - Harvard University
Brian Clagett - Case Western Reserve University
Heather A. Pilch-Cooper - Case Western Reserve University
Benigno Rodriguez - Case Western Reserve University
Judith Feinberg - University of Cincinnati
Eric Daar - The Lundquist Institute
John Mellors - Pittsburg State University
Daniel Kuritzkes - Brigham and Women's Hospital
Jeffrey M. Jacobson - Drexel University
Michael M. Lederman - Case Western Reserve University
Publication Details: PloS one, v 8(12)
Publisher: Public Library Science
Number of pages: 12
Grant note: AI-69501; AI-068636; AI 36219; AI069472; AI060354; UL1 TR000170 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA UL1TR000124 / UCLA CTSI UL1TR000124 / NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS) K99HL108743 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) U01AI069501 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) UM1 AI068634 / National Institute of Allergy and Infectious Diseases; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
Resource Type: Journal article
Language: English
Web of Science ID: WOS:000328740300108
Scopus ID: 2-s2.0-84893171544
Other Identifier: 991019335318304721

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Collaboration types: Domestic collaboration
Web of Science research areas: Immunology

Dynamics of Immune Reconstitution and Activation Markers in HIV plus Treatment-Naive Patients Treated with Raltegravir, Tenofovir Disoproxil Fumarate and Emtricitabine

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