The Role of Immune Reconstitution in the Onset of Subclinical Atheromasic Lesions

Abstract

To the Editors: In recent studies,1-3 patients with low CD4+ cell count showed an increased risk for cardiovascular disease (CVD). A hyperproduction of proinflammatory cytokines (interleukin-6, high sensitivity C-reactive protein [hsPCR]) have been hypothesized in these patients.4 Few data exist regarding the role of immune reconstitution in the onset of CVD, another condition that could be related to an increase of circulating proinflammatory factors. Aimed at the detection of subclinical atheromasic lesions in patients who experienced immune reconstitution, in the present study, we evaluated 263 patients starting antiretroviral therapy (ART) at baseline and after 12 months, with color Doppler ultrasonography of the epiaortic vessels, a well-validated technique, considered the gold standard for the detection of premature vascular lesions. The patients were subjected to color Doppler ultrasonography of the epiaortic vessels using a last-generation power color Doppler instrument with 7.5 mgHz probes (ACUSON sequoia 512). Ultrasonography was performed by physicians specifically trained on carotid vessels and had at least 15 years experience with the ultrasound color Doppler technique and about 10,000 documented epiaortic examinations. They were blinded to the patient's treatment history and status and unaware of the diagnosis of the other colleagues. The patients were placed in a supine position after at least 10 minutes of acclimatization in a comfortable room. They were informed that the investigation was noninvasive. The 2 common carotids, the bifurcations and at least the first 2 cm of the internal and external carotid vessels were examined in the short and long axis during the telediastolic phase (T wave of the electrocardiogram). During the investigation, the head of the patient was hyperextended and extrarotated from the opposite side. The morphological investigation of the plaques was performed using both ultrasonography and the ultrasound power color Doppler to better characterize the profile of the plaque and the intima media thickness. An intima media thickness >0.9 mm and/or the presence of atherosclerotic plaques were considered pathologic findings. After 12 months of ART, patients with <50 CD4+ cell count per cubic millimeter at baseline were divided into 3 groups based on CD4+ at follow-up: group A: patients with <100 CD4+ (# 41); group B: patients with 100-200 CD4+ (# 50); and group C: patients with >200 CD4+ (# 62). The CD4+ cell count was detected on 2 separate occasions, measured sequentially at least 4 weeks apart. The data were compared with those observed in 110 patients starting their 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. All patients were treated with a PI-based therapy. Backbone drugs were well balanced among the groups (Table 1). Statistical analysis was performed using χ2 test. The Ethics Committee of the hospital approved the study, and the patients provided informed consent.TABLE 1: Distribution of Demographics, Risk Factors for CVD, and Antiretroviral Therapies Among the GroupsAs showed in Figure 1, patients with <50 CD4+ cell count at baseline that reached values >200 (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 (P = 0.00001).FIGURE 1: Distribution of subclinical carotid lesions at baseline and at follow-up with statistical analysis.In a previous issue, Williams et al5 observed a higher rate of myocardial infarctions and other symptomatic cardiovascular events in patients experiencing immune reconstitution. Our data show that patients starting ARV with a high degree of immune depression tend to develop more subclinical carotid lesions with respect to patients starting ARV in a relatively better immunologic condition. Moreover, patients experiencing a more rapid immune reconstitution develop a significantly higher number of subclinical vascular lesions. These data suggest that inflammatory events characterizing both immune deficiency and immune reconstitution could play a role in the onset of CVD. Paolo Maggi, MD* Anna Volpe, BD* Chiara Bellacosa, MD* Giuseppe Pastore, MD* Francesco Perilli, MD† Antonio Lillo, MD† Guido Regina, MD† *Clinica delle Malattie Infettive, Università degli Studi di Bari, Italy †Cattedra di Chirurgia Vascolare, Università degli Studi di Bari, Italy