Maraviroc intensification in patients with suppressed HIV viremia has limited effects on CD4+ T cell recovery and gene expression.

Antiviral Res 2014 Jul 24;107:42-9. Epub 2014 Apr 24.

Department of Medicine and Division of Infectious Diseases, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA. Electronic address:

Addition of the CCR5 inhibitor Maraviroc (MVC) to ongoing antiretroviral therapy increases CD4+ T cell counts in some virologically suppressed patients with suboptimal CD4+ T cell recovery. To understand the mechanisms by which MVC elicits increases in CD4+ T cell counts, the present study was undertaken to identify host factors (i.e. genes) that are modulated and are correlated with CD4+ T cell recovery during the 24weeks of MVC intensification in 32 subjects. Median changes of CD4+ T cell counts over 24weeks of MVC compared to baseline were 38cells/mm(3) (p<0.001). The median slope of CD4+ T cell recovery was 39cells/mm(3) per year before initiation of MVC and 76cells/mm(3) per year during MVC intensification, however, this increase was not statistically significant (p=0.33). Microarray analysis (N=31,426 genes) identified a single differentially expressed gene, tumor necrosis factor alpha (TNF), which was modestly (1.44-fold, p<0.001) downregulated by MVC at week 24 compared to baseline. TNF differential expression was evaluated using an independent method of droplet digital PCR, but the difference was not significant (p=0.6). Changes in gene expression did not correlate with CD4+ T cell recovery or any changes in the CD4+ T cell maturation, proliferation and activation phenotypes. In summary, our data suggest that modest improvements of CD4+ T cell counts during MVC intensification cannot be explained by changes in gene expression elicited by MVC. However, the modest changes in T cell composition, including reduction of the percentages of Tregs, proliferating CD4+ T cells and senescent CD8+ T cells, suggest immunologically favorable effects of MVC.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.antiviral.2014.04.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116489PMC
July 2014

Publication Analysis

Top Keywords

cd4+ cell
24
cell recovery
12
cell counts
12
24weeks mvc
8
increases cd4+
8
cell
6
cd4+
6
counts study
4
study undertaken
4
undertaken identify
4
therapy increases
4
elicits increases
4
mvc elicits
4
suboptimal cd4+
4
patients suboptimal
4
virologically suppressed
4
recovery understand
4
understand mechanisms
4
mechanisms mvc
4
identify host
4

Similar Publications