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(Circulation. 2005;112:103-109.)
© 2005 American Heart Association, Inc.

Pediatric Cardiology

Early Structural and Functional Changes of the Vasculature in HIV-Infected Children

Impact of Disease and Antiretroviral Therapy

Marietta Charakida, MD; Ann E. Donald, AVS; Hannah Green, MSc; Clare Storry, BSc, AVS; Margaret Clapson, RGN, RSCN, RHV, BSc; Muriel Caslake, PhD; David T. Dunn, PhD; Julian P. Halcox, MD, MA, MRCP; Diana M. Gibb, MD, MSc; Nigel J. Klein, PhD, FRCPCH; John E. Deanfield, BA, BChir, MB, FRCP

From the Vascular Physiology Unit (M. Charakida, A.E.D., C.S., J.P.H., J.E.D.) and Infectious Diseases and Microbiology Unit (N.J.K.), Institute of Child Health, London (N.J.K.); Medical Research Council Clinical Trials Unit, London (H.G., D.T.D., D.M.G.); Infectious Diseases Unit, Great Ormond Street Hospital for Children, NHS TRUST, London (M. Clapson); Department of Vascular Biochemistry, Division of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow (M. Caslake), UK.

Correspondence to Marietta Charakida, Vascular Physiology Unit, 30 Guilford St, London, WC1N 1EH, UK. E-mail charakidadoc{at}hotmail.com

Received October 26, 2004; revision received February 7, 2005; accepted March 8, 2005.

Background— Premature cardiovascular disease is increasingly recognized in HIV-infected patients, but the mechanisms involved are unclear. The purpose of this study was to determine the impact of HIV infection and antiretroviral therapy (ART) on markers of early vascular disease in children.

Methods and Results— We studied 83 HIV-infected children (56 had taken ART, of whom 31 received a regimen containing protease inhibitors [PIs]; 27 were never treated) and a control group of 59 healthy children. Carotid intima-media thickness (IMT) and brachial artery flow-mediated dilatation (FMD) were measured. IMT was significantly greater in HIV-infected children compared with the control subjects (P<0.001). Among the HIV-infected children, age and treatment were significantly associated with increased IMT. Children exposed to PIs had greater IMT compared with both non-PI-treated children and untreated children (P=0.02). FMD was also significantly reduced in the HIV-infected children compared with control subjects (P=0.02). Pairwise comparisons of different treatment exposure groups revealed that FMD was impaired by a mean of 3.6% (95% CI, 1.8 to 5.3; P<0.001) for children exposed to PIs compared with untreated children and by a mean of 1.8% (95% CI, 0.01 to 3.5; P=0.05) compared with non-PI-treated children. HIV-infected children had lipid abnormalities, but they did not account for the observed differences in either FMD or IMT.

Conclusions— HIV infection in childhood is associated with adverse structural and functional vascular changes that are most pronounced in children exposed to PI therapy. Longitudinal studies are required to differentiate the relative impact of HIV disease and ART and to assess the potential for prevention.

Key Words: endothelium • HIV • protease inhibitors

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