6 years) in the PI group compared with the NNRTI group (35.3 years). The various distinct parameters of apoptosis and viral infection were comparable in the NNRTI- and PI-based treatment groups at baseline. As expected, under successful antiretroviral treatment, the total number of lymphocytes and relative and absolute CD4 T-cell counts increased significantly, with an absolute median increase of 500 cells/μL [interquartile

range (IQR) 270–905 cells/μL] in the PI group and 495 cells/μL (IQR 300–683 cells/μL) in the NNRTI group. The lymphocyte levels of viral Nef mRNA, IFN-α mRNA and IFN-α-inducible MxA mRNA also decreased in both treatment groups, but these changes were not significant except for MxA mRNA in the PI treatment group. No differences between the groups Trichostatin A order in changes in CD4 T-cell counts (relative and absolute), viral activity (Nef) or inflammation (IFN-α and MxA) were observed. Over the study period of 7 years, both treatment groups showed a significant decrease in overall apoptosis [Annexin V+/7-AAD– (per cent of total CD4 T-cells)], as well as in the activity of the click here downstream effector caspase 3/7 and extrinsic apoptosis (caspase 8 activity and TRAIL). The

decrease in FasL mRNA, an inducer of

the extrinsic pathway, was not significant in the PI group. Parameters of intrinsic apoptosis (caspase 9, Bcl-2 protein, Bcl-2 mRNA, Bax mRNA, the lactate-to-pyruvate ratio and the mitochondrial-to-nuclear DNA ratio) changed significantly in the PI group but not Roflumilast in the NNRTI group. However, the most remarkable results obtained related to inter-group differences in the changes. Compared with the NNRTI group, patients treated with the PI-based regimen showed a significantly greater decrease in overall apoptosis and concomitantly significantly greater decreases in proapoptotic parameters of the intrinsic pathway (the mitochondrial-to-nuclear DNA ratio and the lactate-to-pyruvate ratio) and significantly greater increases in antiapoptotic intrinsic markers (Bcl-2 protein, Bcl-2 mRNA and the Bcl-2-to-Bax mRNA ratio). In contrast, changes in parameters of extrinsic apoptosis (caspase 8 activity, TRAIL mRNA and FasL mRNA) showed no differences between the two treatment groups. A multiple stepwise linear regression analysis was conducted to describe predictors of inter-group differences in changes in the mitochondrial-to-nuclear DNA ratio (the primary outcome measure). The following variables were tested: treatment regimen (PI vs.