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

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