CLINICAL SCIENCE Subclinical Atherosclerosis and Markers of Immune Activation in HIV-Infected Children and Adolescents: The CaroVIH Study Talía Sainz, MD,*† María Álvarez-Fuente, MD,‡ María Luisa Navarro, MD, PhD,† Laura Díaz, PhD,* Pablo Rojo, MD, PhD,§ Daniel Blázquez, MD,§ María Isabel de José, MD, PhD,k José Tomás Ramos, MD, PhD,¶ Sergio Serrano-Villar, MD, PhD,# Jorge Martínez, MD,** Constancio Medrano, MD,‡ María Ángeles Muñoz-Fernández, MD, PhD,* and María José Mellado, MD, PhD†† on behalf of the Madrid Cohort of HIV-infected children and adolescents integrated in the Pediatric branch of the Spanish National AIDS Network (CoRISPE) Background: HIV-infected adults display increased cardiovascu- lar 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 (CD28 2 CD57 + ) 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 6 0.025 vs. 0.424 mm 6 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. Key Words: HIV, adolescents, cardiovascular risk factors, IMT, immune activation (J Acquir Immune Defic Syndr 2014;65:42–49) INTRODUCTION Because patients treated with antiretroviral drugs live longer and have to deal with the complications of aging, much attention is turning to the so called “non-AIDS”–related pathologies; a group of conditions generally associated to aging, including cardiovascular disease (CVD), renal impair- ment, hepatic disease, osteoporosis, and non-AIDS–defining malignancies. 1 As the mean age of HIV-infected individuals is progressively increasing, CVD is likely to gain further importance as a cause of mortality in years to come. 2 Despite being the focus of intense investigation, the etiology of the increased cardiovascular risk in this population remains unclear, most probably because of a multifactorial pathophys- iology. 1 Indeed, it is difficult to fully isolate the weight of the different proatherogenic factors in the presence of classical Received for publication May 23, 2013; accepted August 12, 2013. From the *Laboratorio de InmunoBiología Molecular, Hospital General Uni- versitario 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, Servi- cio de Pediatría, Hospital Universitario Doce de Octubre, Madrid, Spain; kServicio de Pediatría, Hospital Universitario La Paz, Madrid, Spain; ¶Ser- vicio de Pediatría, Hospital de Getafe, Madrid, Spain; #Servicio de Enfer- medades 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. 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 pro- vided 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 pre- vención 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). 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). Copyright © 2013 by Lippincott Williams & Wilkins 42 | www.jaids.com J Acquir Immune Defic Syndr  Volume 65, Number 1, January 1, 2014