Subclinical Atherosclerosis and Markers of Immune Activation in HIV-Infected Children and Adolescents: The CaroVIH Study

Sainz, Talía MD*,†; Álvarez-Fuente, María MD; Navarro, María Luisa MD, PhD; Díaz, Laura PhD*; Rojo, Pablo MD, PhD§; Blázquez, Daniel MD§; Isabel de José, María MD, PhD; Ramos, José Tomás MD, PhD; Serrano-Villar, Sergio MD, PhD#; Martínez, Jorge MD**; Medrano, Constancio MD; Muñoz-Fernández, María Ángeles MD, PhD*; Mellado, María José MD, PhD††

JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0b013e3182a9466a
Clinical Science
Abstract

Background: HIV-infected adults display increased cardiovascular disease, probably driven by inflammation and immune activation. These relationships have not been addressed in vertically HIV-infected children and adolescents, a population at very high risk for long-term non-AIDS complications.

Methods: Carotid intima media thickness (IMT) was measured in a cohort of HIV-infected children and adolescents and healthy controls. C-reactive protein and markers of immune activation (CD38+HLA-DR+) and immune senescence (CD28CD57+) were determined.

Results: One hundred fifty HIV-infected patients and 150 controls were included, 64.8% female. IMT was thicker in HIV-infected patients (0.434 mm ± 0.025 vs. 0.424 mm ± 0.018, P < 0.001). After adjustment by age, sex, body mass index, and smoking status, HIV infection was independently associated with thicker IMT (odds ratio, 2.28; 95% confidence interval: 1.25 to 4.13; P = 0.007). Among HIV-related variables, a low CD4 nadir was related to an increased IMT. Although HIV-infected subjects presented higher frequencies of activated CD4+ and CD8+ T cells (P = 0.002 and P = 0.087, respectively), no relation was found between IMT and inflammation, immune activation, or senescence.

Conclusions: Structural changes of the vasculature present early in vertically HIV-infected subjects as well as immune activation and senescence. These patients should be carefully monitored for the prompt detection and early treatment of cardiovascular disease.

Author Information

*Laboratorio de InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón e Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain;

Unidad de Enfermedades Infecciosas, Servicio de Pediatría, Hospital General Universitario Gregorio Marañón, Madrid, Spain;

Unidad de Cardiología Infantil, Hospital General Universitario Gregorio Marañón, Madrid, Spain;

§Unidad de Inmunodeficiencias, Servicio de Pediatría, Hospital Universitario Doce de Octubre, Madrid, Spain;

Servicio de Pediatría, Hospital Universitario La Paz, Madrid, Spain;

Servicio de Pediatría, Hospital de Getafe, Madrid, Spain;

#Servicio de Enfermedades Infecciosas, Hospital Universitario Ramón y Cajal, and IRYCIS, Madrid, Spain;

**Servicio de Pediatría, Hospital Universitario Niño Jesús, Madrid, Spain; and

††Servicio de Pediatría, Hospital Carlos III, Madrid, Spain.

Correspondence to: Talía Sainz Costa, MD, Laboratorio de Inmunobiología Molecular, Hospital Gregorio Marañón, C/Dr Esquerdo 46, 28007 Madrid, Spain (e-mail: tsainzcosta@gmail.com).

Partially supported by a Small Grant Award from the European Society of Pediatric Infectious Diseases and by the Spanish Ministry of Science and Innovation (FIS, grant no PI12/01483). Philips Healthcare kindly provided portable ultrasound equipment for the purpose of the study. T.S. and S.S.-V. are funded by grants from the Spanish Ministry of Science and Innovation (Ayudas para Contratos de Formación en Investigación Río Hortega). L.D. is cofunded by the Spanish Ministry of Science and Innovation. The Pediatric HIV BioBank, integrated in the Spanish AIDS Research Network, is supported by Instituto de Salud Carlos III, Spanish Health Ministry (grant no RD06/0006/0035). The Madrid Cohort of HIV-infected Children is supported by Fundación para la investigación y prevención del SIDA en España (grant no 360829-09).

The authors have no conflicts of interest to disclose.

Presented at 19th Conference on Retrovirus and Opportunistic Infections, CROI, March 5–8, 2012, Seattle, WA (ref. 971), 61st Congress of the Spanish Society of Pediatrics, AEPED, May 31–June 2, 2012, Granada, Spain (ref. C145), and 30th Congress of the European Society of Pediatric Infectious Diseases, European Society of Pediatric Infectious Diseases, May 8–12, 2012, Thessaloniky, Greece (ref. 967).

Received May 23, 2013

Accepted August 12, 2013

© 2014 by Lippincott Williams & Wilkins