Effects of Highly Active Anti-Retroviral Therapy on Cardiovascular Health in Infants of HIV-Infected Mothers

NCT ID: NCT00253682

Last Updated: 2014-03-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

167 participants

Study Classification

OBSERVATIONAL

Study Start Date

2002-09-30

Study Completion Date

2006-12-31

Brief Summary

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This study will determine the impact of highly active antiretroviral therapy (HAART) on the developing cardiovascular system, the evolution of HAART-associated cardiovascular changes over time, and the association between cardiovascular measurements with HAART exposure.

Detailed Description

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BACKGROUND:

HIV-infected pregnant women frequently receive HAART, which 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), representing the majority of infants in the United States exposed to HAART. Long-term consequences and toxicities associated with this exposure are not known, but severe cardiotoxicity is suggested in animal models. This study will utilize HIV seroreverter cohorts from the NIH-sponsored Women and Infants Transmission Study (WITS) and Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infections Study (P2C2) 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. In P2C2, patients were recruited from May 1990 to January 1994 from five clinical centers in the United States.

This study was initiated in 2002 in response to a 'Request for Applications' on HAART cardiovascular toxicities.

DESIGN NARRATIVE:

This study will utilize HIV seroreverter cohorts from the NIH-sponsored WITS and P2C2 cohorts to determine how LV structure and function, cTnT, proBNP, and hsCRP are affected by HAART exposure. The p2C2 seroreverter cohort has been exposed to no antiretroviral therapy or zidovudine alone (without HAART) and has persistent significantly depressed LV contractility in comparison to normal with up to 5 years of follow-up. The WITS seroreverter cohort has been exposed mostly to HAART. This cohort will determine the incremental effect of HAART on LV structure and function by following the P2C2 protocol for assessment of LV structure and function. This study will test three hypotheses: 1) that HAART exposure results in fetal and neonatal myocardiocyte injury and death (by serial assessment of cTnT \[a biomarker of acute myocardial injury\] in both seroreverter cohorts); 2) that HAART exposure results in impaired myocardiocyte mitochondrial function resulting in LV dysfunction (by serial assessment of proBNP \[a biomarker related to LV dysfunction\], LV volume and pressure increases resulting in LV stretch, and neurohormonal activation); and 3) that HAART exposure results in accelerated atherosclerosis (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.

Conditions

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Cardiovascular Diseases Heart Diseases Atherosclerosis HIV Infections Cardiomyopathy, Hypertrophic

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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1

HIV-uninfected infants born to HIV-infected women with in-utero exposure to HIghly Active Ani-Retroviral Therapy (HAART) who were enrolled in the Women and Infants Transmission Study (WITS).

No interventions assigned to this group

2

Historical cohort of HIV-uninfected infants born to HIV-infected women from the Pediatric Pulmonary and Cardiovascular Complications of HIV Study (P2C2 HIV) who were not exposed to HAART.

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* Children who are actively enrolled in the WITS study, regardless of whether or not they have been exposed to HAART therapy
* Children enrolled into this study from one of the designated WITS clinical sites
* Mothers or legal guardians understand and are willing to provide informed consent with or without the help of an interpreter

Exclusion Criteria

* Children diagnosed with HIV infection
* Mother has maternal diabetes or phenylketonuria
* Mother has been told by a physician that she has chromosomal defects
* Mother has functional heart defects that have required medications or surgeries
* Mother received cancer chemotherapy or radiation therapy during pregnancy
* Mother used lithium carbonate, anticonvulsants, amphetamines, or angiotensin converting enzyme (ACE) inhibitors during pregnancy
Maximum Eligible Age

2 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Baylor College of Medicine

OTHER

Sponsor Role collaborator

University of Illinois at Chicago

OTHER

Sponsor Role collaborator

Clinical Trials & Surveys Corp (C-TASC)

INDUSTRY

Sponsor Role collaborator

Columbia University

OTHER

Sponsor Role collaborator

Boston Medical Center

OTHER

Sponsor Role collaborator

University of Miami

OTHER

Sponsor Role lead

Responsible Party

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Steven E. Lipshultz, MD

Voluntary Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Steven E. Lipshultz, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Locations

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University of Miami School of Medicine

Miami, Florida, United States

Site Status

University of Illinois - Chicago

Chicago, Illinois, United States

Site Status

Boston Medical Center

Boston, Massachusetts, United States

Site Status

Columbia University

New York, New York, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

Countries

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United States

References

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Seeborg FO, Gay H, Schmiege LM 3rd, Bernard D, Shearer WT. Immunoglobulin G kappa [IgG kappa] and IgG lambda paraproteinemia in a child with AIDS and response to highly active antiretroviral therapy. Clin Diagn Lab Immunol. 2005 Nov;12(11):1331-3. doi: 10.1128/CDLI.12.11.1331-1333.2005.

Reference Type BACKGROUND
PMID: 16275950 (View on PubMed)

Shearer WT. Infection versus immunity: What's the balance? J Allergy Clin Immunol. 2005 Aug;116(2):263-6. doi: 10.1016/j.jaci.2005.06.001. No abstract available.

Reference Type BACKGROUND
PMID: 16083777 (View on PubMed)

Simbre VC, Duffy SA, Dadlani GH, Miller TL, Lipshultz SE. Cardiotoxicity of cancer chemotherapy: implications for children. Paediatr Drugs. 2005;7(3):187-202. doi: 10.2165/00148581-200507030-00005.

Reference Type BACKGROUND
PMID: 15977964 (View on PubMed)

Lipshultz SE, Lipsitz SR, Sallan SE, Dalton VM, Mone SM, Gelber RD, Colan SD. Chronic progressive cardiac dysfunction years after doxorubicin therapy for childhood acute lymphoblastic leukemia. J Clin Oncol. 2005 Apr 20;23(12):2629-36. doi: 10.1200/JCO.2005.12.121.

Reference Type BACKGROUND
PMID: 15837978 (View on PubMed)

Moylett EH, Hanson IC. Mechanistic actions of the risks and adverse events associated with vaccine administration. J Allergy Clin Immunol. 2004 Nov;114(5):1010-20; quiz 1021. doi: 10.1016/j.jaci.2004.09.007.

Reference Type BACKGROUND
PMID: 15536401 (View on PubMed)

Shearer WT. Importance of technology for the future of allergy and immunology. J Allergy Clin Immunol. 2004 Aug;114(2):406-8. doi: 10.1016/j.jaci.2004.06.031. No abstract available.

Reference Type BACKGROUND
PMID: 15316524 (View on PubMed)

Seeborg FO, Paul ME, Abramson SL, Kearney DL, Dorfman SR, Holland SM, Shearer WT. A 5-week-old HIV-1-exposed girl with failure to thrive and diffuse nodular pulmonary infiltrates. J Allergy Clin Immunol. 2004 Apr;113(4):627-34. doi: 10.1016/j.jaci.2004.01.763.

Reference Type BACKGROUND
PMID: 15100665 (View on PubMed)

Mone SM, Gillman MW, Miller TL, Herman EH, Lipshultz SE. Effects of environmental exposures on the cardiovascular system: prenatal period through adolescence. Pediatrics. 2004 Apr;113(4 Suppl):1058-69.

Reference Type BACKGROUND
PMID: 15060200 (View on PubMed)

Nance CL, Shearer WT. Is green tea good for HIV-1 infection? J Allergy Clin Immunol. 2003 Nov;112(5):851-3. doi: 10.1016/j.jaci.2003.08.048. No abstract available.

Reference Type BACKGROUND
PMID: 14610469 (View on PubMed)

Al-Attar I, Orav EJ, Exil V, Vlach SA, Lipshultz SE. Predictors of cardiac morbidity and related mortality in children with acquired immunodeficiency syndrome. J Am Coll Cardiol. 2003 May 7;41(9):1598-605. doi: 10.1016/s0735-1097(03)00256-0.

Reference Type BACKGROUND
PMID: 12742303 (View on PubMed)

Other Identifiers

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R01HL072705

Identifier Type: NIH

Identifier Source: secondary_id

View Link

342

Identifier Type: -

Identifier Source: org_study_id

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