Effects of Highly Active Anti-Retroviral Therapy on Cardiovascular Health in Infants of HIV-Infected Mothers (CHAART-1)

This study has been completed.
Sponsor:
Collaborators:
Baylor College of Medicine
University of Illinois at Chicago
Clinical Trials & Surveys Corp (C-TASC)
Columbia University
Boston Medical Center
Information provided by (Responsible Party):
Steven E. Lipshultz, MD, University of Miami
ClinicalTrials.gov Identifier:
NCT00253682
First received: November 10, 2005
Last updated: March 17, 2014
Last verified: March 2014

November 10, 2005
March 17, 2014
September 2002
December 2006   (final data collection date for primary outcome measure)
Not Provided
Not Provided
Complete list of historical versions of study NCT00253682 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Effects of Highly Active Anti-Retroviral Therapy on Cardiovascular Health in Infants of HIV-Infected Mothers
Cardiac Status of HAART Exposed Infants of HIV-Infected Mothers (CHAART I)

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.

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.

Observational
Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Retention:   Samples Without DNA
Description:

Blood samples were collected for analysis of cardiac biomarkers high sensitivity C REactive PRotein (hsCRP) and N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP).

Non-Probability Sample

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).

The comparison group will be a 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.

  • Cardiovascular Diseases
  • Heart Diseases
  • Atherosclerosis
  • HIV Infections
  • Cardiomyopathy, Hypertrophic
Not Provided
  • 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).
  • 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
167
December 2006
December 2006   (final data collection date for primary outcome measure)

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
Both
up to 2 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00253682
342, R01HL072705
Yes
Steven E. Lipshultz, MD, University of Miami
University of Miami
  • National Heart, Lung, and Blood Institute (NHLBI)
  • Baylor College of Medicine
  • University of Illinois at Chicago
  • Clinical Trials & Surveys Corp (C-TASC)
  • Columbia University
  • Boston Medical Center
Principal Investigator: Steven E. Lipshultz, MD University of Miami
University of Miami
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP