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The effect of antiretroviral treatment on selected genes in whole blood from HIV-infected adults sensitised by Mycobacterium tuberculosis

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Title: The effect of antiretroviral treatment on selected genes in whole blood from HIV-infected adults sensitised by Mycobacterium tuberculosis
Authors: Jhilmeet, N
Lowe, DM
Riou, CR
Scriba, TJ
Coussens, AK
Goliath, RT
Wilkinson, RJ
Wilkinson, KA
Item Type: Journal Article
Abstract: HIV-1 co-infection is a leading cause of susceptibility to tuberculosis (TB), with the risk of TB being increased at all stages of HIV-1 infection. Antiretroviral treatment (ART) is the most effective way to reduce the risk of TB in HIV-1 co-infected people. Studying protective, ART-induced, immune restoration in HIV-1 infected individuals sensitised by Mycobacterium tuberculosis (Mtb) can thus help identify mechanisms of protection against TB. In order to understand ART-mediated prevention of TB in HIV-1 infected adults, we investigated the expression of 30 genes in whole blood from HIV-1 infected patients during the first 6 months of ART-induced immune reconstitution. The 30 selected genes were previously described to be differentially expressed between sorted Mtb specific central and effector memory CD4 T cells. HIV-1 infected persons sensitised by Mtb were recruited in Khayelitsha, South Africa, when initiating ART. RNA was extracted from whole blood at initiation and 1, 3 and 6 months of ART. qRT-PCR was used to determine gene expression and three reference ‘housekeeping’ genes were used to calculate the fold change in the expression of each gene relative to day 0 of ART. Results were assessed longitudinally. We observed a decrease in the expression of a number of genes at 6 months of ART, reflecting a decrease in immune activation. However, following correction for multiple comparisons and increasing CD4 counts, only the decrease in CD27 gene expression remained statistically significant. While not statistically significant, a number of genes also showed increased expression at various timepoints, illustrating the broad regeneration of the T cell pool in HIV-1 infected adults on ART. Our findings generate hypotheses underlying ART- induced protective immune reconstitution and may pave the way for future studies to evaluate ART mediated prevention of TB in HIV-1 infected persons.
Issue Date: 27-Dec-2018
Date of Acceptance: 6-Dec-2018
URI: http://hdl.handle.net/10044/1/66688
DOI: https://dx.doi.org/10.1371/journal.pone.0209516
ISSN: 1932-6203
Publisher: Public Library of Science (PLoS)
Journal / Book Title: PLoS ONE
Volume: 13
Issue: 12
Copyright Statement: © 2018 Jhilmeet et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Sponsor/Funder: Wellcome Trust
Wellcome Trust
Funder's Grant Number: 087754/Z/08/Z
104803/Z/14/ZR
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
CD4(+) T-CELLS
EXPRESSION
THERAPY
RESPONSES
MD Multidisciplinary
General Science & Technology
Publication Status: Published
Article Number: e0209516
Appears in Collections:Department of Medicine
Faculty of Medicine



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