Seroreverters Perinatally Exposed to HAART 187 Cardiovascular Toxicology Humana Press Volume 4, 2004 187 *Author to whom all correspondence and reprint requests should be addressed: Steven E. Lipshultz, MD, University of Miami, P.O. Box 016820, Miami, FL 33101. E-mail: slipshultz@med.miami.edu. Received: 12/17/2003 Revised: 2/25/2004 Accepted: 2/25/2004 Cardiovascular Toxicology, vol. 4, no. 2, 187–197, 2004 Cardiovascular Outcomes of Pediatric Seroreverters Perinatally Exposed to HAART Design of a Longitudinal Clinical Study Jill E. Lavigne, 1 William T. Shearer, 2 Bruce Thompson, 3 E. John Orav, 4 Thomas J. Starc, 5 Steven D. Colan, 6 Ricardo Pignatelli, 2 Sharon E. O’Brien, 8 Louis Bezold, 2 Phillip LaRusa, 5 Kirk A. Easley, 6 Irene Cheng, 3 Sarah A. Duffy, 7 and Steven E. Lipshultz 7, * for the CHAART Study Group 1 University of Rochester, Rochester, NY; 2 Baylor College of Medicine and Texas Children’s Hospital, Houston, TX; 3 Clinical Trials and Survey Corporation, Baltimore, MD; 4 Brigham & Women’s Hospital, Boston, MA; 5 Columbia University, New York, NY; 6 Boston Children’s Hospital, Boston, MA; 7 University of Miami, Miami, FL; and 8 Boston Medical Center, Boston, MA Cardiovascular Toxicology (2004) 04 187–197 $25.00 (http://www.cardiotox.com) © Copyright 2004 by Humana Press Inc. All rights of any nature whatsoever reserved. 1530-7905/01 Humana Press Abstract Seroreverters (uninfected children of HIV-infected mothers) have exhib- ited left ventricular (LV) dysfunction. Mitochondrial toxicity associated with in utero or postnatal exposure to highly active antiretroviral therapy (HAART) is a possible mechanism. Adult and animal models have demonstrated associ- ations between LV abnormalities, cardiomyopathy, and components of HAART. Yet, outcomes in children are poorly understood. In this study, we explore HAART- associated LV abnormalities in seroreverters exposed to HAART (n = 144) or never exposed (n = 252). Subjects are drawn from the Women and Infants Transmission Study and the Pediatric Pulmonary and Cardiovascular Com- plications of HIV Study, respectively. Data include (1) echocardiographic studies of LV structure and function and (2) serologic cardiac biomarkers (car- diac troponin, probrain natriuretic peptide, high-sensitivity C reactive protein), both collected during the first month of life, and again at 6, 12, 24, 36, and 48 months postnatally. Planned analyses include several regression models. At this time, we have access to data for all 252 unexposed children, and 53 exposed subjects are enrolled. The cohorts are similar in terms of gender and race and the recruited subjects are representative of all eligible subjects in terms of exposure to HAART. Recruitment will continue into 2006. Key Words: Highly active antiretroviral therapy; HIV; toxicity; cardiovascu- lar; seroreverter; prophylaxis; antiretroviral therapy; vertical transmission; study design; mitochondria. Introduction Recently, antiretroviral therapy (ART) was shown to be independently associated with a small but significant increase in the rate of myocardial infarction in adults