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

Jhilmeet, N; Lowe, DM; Riou, C; Scriba, TJ; Coussens, A; Goliath, R; Wilkinson, RJ; Wilkinson, KA

Author(s): Jhilmeet, N; Lowe, DM; Riou, C; Scriba, TJ; Coussens, A; Goliath, R; Wilkinson, RJ; Wilkinson, KA;
Details: Publication Year 2018,Volume 13,Issue #12,Page e0209516
Journal Title: PLoS One
Publication 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.
Publisher: PLOS
Research Division(s): Infectious Diseases And Immune Defence
PubMed ID: 30589870
Publisher's Version: https://doi.org/10.1371/journal.pone.0209516
Open Access at Publisher's Site: https://doi.org/10.1371/journal.pone.0209516
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2020-01-21 11:05:23

Last Modified: 2020-02-10 04:58:18