Increased Subclinical Atherosclerosis and Immune Activation in HIV+ Children and Adolescents: The CaroVIH Study
Talia Sainz1, L Diaz1, M Álvarez1, ML Navarro1, MI González-Tomé2, MI de José3, J Ramos4, S Serrano-Villar5, MA Munoz-Fernandez1, and MJ Mellado6
1Hosp Gregorio Marañón, Madrid, Spain; 2Hosp 12 de Octubre, Madrid, Spain; 3Hosp La Paz, Madrid, Spain; 4Hosp de Getafe, Madrid, Spain; 5Hosp Clin San Carlos, Madrid, Spain; and 6Hosp Carlos III, Madrid, Spain
Background: HIV patients present early cardiovascular disease (CVD). The study of subclinical atherosclerosis in subjects without CVD risk factors, such as children and adolescents, may help to clarify the specific influence of HIV infection on the atherogenic process. It is unknown if the recently described association between T cell activation and senescence with carotid artery abnormalities is already present in childhood.
Methods: Carotid intima-media thickness (IMT) was measured in 122 HIV+ children and young adults and 53 healthy controls matched by age, sex, and body mass index. Markers of immune activation (CD38+HLADR+) and immune senescence (CD57+CD28–) were determined in a subgroup of 34 HIV patients and 11 controls.
Results: The mean age of the HIV+ and HIV– subjects was 14.9 years (range 2.5 to 23.8) and 13.6 (range 2.9 to 22.6), respectively; smokers 15.5% vs 5.7%. Most HIV+ patients were female (64.8%), had undetectable viral load (76.4%), and were vertically HIV-infected (96.7%); all but 2 patients were on HAART. IMT was thicker in HIV+ patients than in HIV–subjects (0.434±0.025 mm vs 0.424±0.018, respectively). After adjustment by age, sex, body mass index, and smoking status, HIV infection was independently associated with thicker IMT (odds ratio, 2.7; 95% confidence interval, 1.4 to 5.5; p = 0.004). Among HIV-related variables, only a lower CD4 nadir was related to increased IMT (Spearman rho = –0.18; p = 0.055). Compared with HIV– subjects, frequencies of activated T CD4+ cells were higher among HIV+ children and young adults (p = 0.002), with a border-line statistical significance for activated CD8+ cells (p = 0.087) and senescent T CD4+ and T CD8+ cells. Viremic patients had the highest frequency of CD4+ and CD8+ activation and senescence, compared to patients with undetectable viral load and control subjects (p <0.05). In the subgroup of viremic patients, those with increased IMT (above the median) showed a higher frequency of activated T CD4 cells (5.6 vs 2.3) and T CD8 cells (25.0 vs 19.0) that did not reach statistical significance.
Conclusions: In our study of children and young adults, there was a 3-fold increased risk of higher IMT due to HIV. The effect of the immunological status seems to be stronger than the effect of age in the early stages of life. Larger studies are warranted to evaluate the role of HIV-induced immune activation in the acceleration of atherogenesis since childhood.