Abstract

HIV-infected pregnant women frequently receive HAART therapy that is associated with reduced maternal-fetal transmission of HIV infection. This has resulted in a rapidly increasing number of seroreverters (HIV-uninfected infants born to HIV-infected women). This represents the majority of infants in the United States exposed to HAART. The long-term consequences and toxicities associated with this exposure are not known but severe cardiotoxicity is suggested in animal models. This study will utilize the NIH-sponsored WITS and p2C2 HIV seroreverter cohorts to determine how left ventricular (LV) structure and function, serum cardiac troponin T (cTnT), serum pro brain natriuretic peptide (proBNP), and serum high sensitivity C reactive protein (hsCRP) are affected by HAART exposure. The p2C2 seroreverter cohort has been exposed to no antiretroviral therapy or zidovudine alone (no HAART) and has persistent significantly depressed LV contractility compared to normal with up to 5 years of follow-up. The WITS seroreverter cohort has been exposed mostly to HAART and, by following the P2C2 protocol for assessment of LV structure and function, will determine the incremental effect of HAART on LV structure and function. The hypothesis that HAAT results in fetal and neonatal myocardiocyte injury and death will be tested by serial assessment of cTnT, a biomarker of acute myocardial injury, in both seroreverter cohorts. The hypothesis that HAART results in impaired myocardiocyte mitochondrial function resulting in LV dysfunction will be tested by serial assessment of proBNP, a biomarker related to LV dysfunction, LV volume and pressure increases resulting LV stretch, and to neurohormonal activation. The hypothesis that HAART results in accelerated atherosclerosis will be tested by serial assessment of hsCRP, a biomarker of generalized inflammation predictive of increased subsequent coronary artery disease. This study will determine the cardiovascular effects of HAART in seroreverters and the need for future cardiovascular follow-up and cardiovascular preventive and therapeutic trials in this rapidly expanding population.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL072705-04
Application #
6788823
Study Section
Special Emphasis Panel (ZHL1-CSR-D (S2))
Program Officer
Goldberg, Suzanne H
Project Start
2002-09-30
Project End
2007-07-31
Budget Start
2004-08-01
Budget End
2005-07-31
Support Year
4
Fiscal Year
2004
Total Cost
$1,247,207
Indirect Cost

  Institution

Name
University of Miami School of Medicine
Department
Pediatrics
Type
Schools of Medicine
DUNS #
052780918
City
Miami
State
FL
Country
United States
Zip Code
33146

  Publications

Bansal, Neha; Barach, Paul; Amdani, Shahnawaz M et al. (2018) When is early septal myectomy in children with hypertrophic cardiomyopathy justified? Transl Pediatr 7:362-366
Lipshultz, Steven E (2018) Letter by Lipshultz Regarding Article, ""Anthracycline Cardiotoxicity: Worrisome Enough to Have You Quaking?"" Circ Res 122:e62-e63
Hutchins, Kelley K; Siddeek, Hani; Franco, Vivian I et al. (2017) Prevention of cardiotoxicity among survivors of childhood cancer. Br J Clin Pharmacol 83:455-465
Lipshultz, Steven E; Anderson, Lynn M; Miller, Tracie L et al. (2016) Impaired mitochondrial function is abrogated by dexrazoxane in doxorubicin-treated childhood acute lymphoblastic leukemia survivors. Cancer 122:946-53
Franco, Vivian I; Lipshultz, Steven E (2015) Cardiac complications in childhood cancer survivors treated with anthracyclines. Cardiol Young 25 Suppl 2:107-16
Lipshultz, Steven E; Franco, Vivian I; Miller, Tracie L et al. (2015) Cardiovascular disease in adult survivors of childhood cancer. Annu Rev Med 66:161-76
Lipshultz, Steven E; Chandar, Jayanthi J; Rusconi, Paolo G et al. (2014) Issues in solid-organ transplantation in children: translational research from bench to bedside. Clinics (Sao Paulo) 69 Suppl 1:55-72
Lipshultz, Steven E; Lipsitz, Stuart R; Kutok, Jeffery L et al. (2013) Impact of hemochromatosis gene mutations on cardiac status in doxorubicin-treated survivors of childhood high-risk leukemia. Cancer 119:3555-62
Landy, David C; Lipsitz, Stuart R; Kurtz, Joy M et al. (2013) Dietary quality, caloric intake, and adiposity of childhood cancer survivors and their siblings: an analysis from the cardiac risk factors in childhood cancer survivors study. Nutr Cancer 65:547-55
Landy, David C; Miller, Tracie L; Lipsitz, Stuart R et al. (2013) Cranial irradiation as an additional risk factor for anthracycline cardiotoxicity in childhood cancer survivors: an analysis from the cardiac risk factors in childhood cancer survivors study. Pediatr Cardiol 34:826-34

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