Background:  In recent studies (SMART, MACS, WIHS) patients with low CD4⁺ cell count showed an increased risk for cardiovascular disease (CVD). Hyper-production of pro-inflammatory cytokines (interleukin-6, highly sensitive C-reactive protein) has been hypothesized in these patients. No data exist regarding the role of immune reconstitution in the onset of CVD, another condition that could be related to an increase of circulating pro-inflammatory factors. In the present study we evaluated 263 patients starting ART at baseline and after 12 months, with color Doppler ultrasonograpy of the epiaortic vessels, a well-validated technique, considered the gold standard for the detection of premature vascular lesions.

Methods:  Patients were submitted to color Doppler ultrasonography at baseline and after 12 months of therapy. An intima media thickness >0.9 mm or atherosclerotic plaques was considered a pathologic finding. After 12 months of ART, patients with <50 CD4⁺ cell count/mm³ at baseline were divided into 3 groups based on CD4⁺ at follow-up:  A) patients with <100 CD4⁺ (n = 41); B) patients with 100 to 199 CD4⁺ (n = 50), and C) patients with >200 CD4⁺ (n = 62). The data were compared with those observed in 110 patients starting ART with >200 CD4⁺ and remaining at follow-up, over this value (group D).The 4 groups were comparable for gender, mean age, and other risk factors for CVD. ARV drugs were well balanced among the groups.

Results:

As showed in the table, patients with <50 CD4⁺ cell count at baseline who reached values >100 (group C) showed a significant increase in the number of carotid lesions at follow-up. Moreover, comparing patients with <50 cells at baseline (groups A+B+C) with patients with >200 cells (group D), the first group had a significant increase of lesions with respect to group D.  

Conclusions:  These data show that patients starting ARV with a high degree of immune depression tend to develop more lesions than patients starting ARV in a relatively better immunologic conditions. Moreover, patients experiencing more rapid immune reconstitution develop a significantly higher number of subclinical vascular lesions. This suggests that inflammatory events characterizing both immune deficiency and immune reconstitution could play a role in the onset of CVD.