Do viral load and CD8 cell count at initiation of tritherapy influence the increase of CD4 T-cell count?

Abstract

Tritherapies including protease inhibitors improve clinical status and usually increase CD4 T cell count. However, the dissociation between the marked decreases in viral load and the incomplete restoration of CD4 cell counts with a three-drug combination has been reported. We assessed this potential difference among our patients. Patients were enrolled when a protease inhibitor was prescribed to them for the first time. Using a computerized medical record (ADDIS), we retrospectively assessed a potential relationship between the increase in CD4 T cells (deltaCD4) at M3, M6 and variables including sex, age, CDC staging, protease inhibitor, prior antiviral therapy, CD8 and viral load at baseline. We used Epi-Info 6.4 and BMDP software. Data were analyzed on 154 patients. The median CD4 T cell count was 157 at baseline, 215 at month 3 and 202 at month 6. The median viral load was 52000 copies at baseline, 530 at month 3 and 500 at month 6. In a univariate analysis, a significant relationship was found between deltaCD4 and CD8 at baseline. A statistically significant negative correlation appeared between the CD8 cell count at baseline and deltaCD4 at M6 (r=-0.28, Pearson). Moreover, we found that there also was a relationship between deltaCD4 and viral load at baseline. There was a correlation between deltaCD4 at M6 and the viral load at M0 (r=0.37, Pearson). In a multiple regression model, after CD8 count at baseline had been accounted for, we found a significant correlation between deltaCD4 and viral load at baseline (multiple r=0.33 at M3, and 0.40 at M6). Patients with a low viral load do not benefit from as great an increase in CD4 T cell count as others when they receive a tritherapy including protease inhibitors. These results suggest that another mechanism rather than direct viral pathogenicity leads to CD4 T cell destruction. This mechanism may not be efficiently stopped by antiviral therapy, especially protease inhibitors.