Long-term Effects of Highly Active Anti-Retroviral Therapy on HIV-Infected Children

This study has been completed.
Sponsor:
Collaborators:
Clinical Trials & Surveys Corp (C-TASC)
Baylor College of Medicine
University of Illinois at Chicago
Columbia University
Boston Medical Center
Children's Hospital Boston
University of Puerto Rico
State University of New York
Information provided by (Responsible Party):
Steven E. Lipshultz, MD, University of Miami
ClinicalTrials.gov Identifier:
NCT00260806
First received: December 1, 2005
Last updated: March 17, 2014
Last verified: March 2014
  Purpose

This study will use the NIH-sponsored Women and Infants Transmission Study (WITS) and the Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infection (P2C2) HIV-infected pediatric cohorts to determine how left ventricular (LV) function (particularly fractional shortening and contractility) and structure (particularly wall thickness and mass) are affected by cumulative intensity of exposure to highly active anti-retroviral therapy (HAART).


Condition
HIV Infections

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: HAART Associated Cardiotoxicity in HIV-Infected Children

Resource links provided by NLM:


Further study details as provided by University of Miami:

Primary Outcome Measures:
  • Cardiac systolic function [ Time Frame: Measured from 2 years of age to 18 years of age ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Peripheral blood mononuclear cells (PBMCs) were collected from the WITS cohort to investigate the presence of mitochondrial DNA (mtDNA) mutations.


Enrollment: 71
Study Start Date: August 2004
Study Completion Date: June 2006
Primary Completion Date: June 2006 (Final data collection date for primary outcome measure)
Groups/Cohorts
1
Children perinatally infected with HIV with exposure to highly active anti-retroviral therapy (HAART).
2
Children with perinatally acquired HIV infection enrolled on the P2C2 Study, not exposed to HAART therapy.

Detailed Description:

BACKGROUND:

HIV-infected children are often given HAART to reduce HIV-associated disease. The long-term effects and toxicities associated with this chronic therapy in children are unknown, but severe cardiotoxicity has been suggested in animal models.

DESIGN NARRATIVE:

The P2C2 HIV-infected pediatric cohort received non-HAART regimens in various intensities. Yet, this cohort has exhibited persistent and significant depression of LV contractility compared to uninfected children (after 5 years of follow-up). These same echocardiographic measures have proven to be independently predictive of mortality. Most of the children in the WITS HIV-infected pediatric cohort have been exposed to HAART at varying times and at varying regimen intensities. By assessing LV structure and function, with the same echocardiographic protocol in the WITS cohort as was used previously in the P2C2 cohort, the study will be able to determine the incremental effects of HAART and non-HAART regimens on LV structure and function. The study will also test the hypothesis that HAART exposure results in impaired mitochondrial function that results in cardiomyopathy. This will be assessed by comparing the parameters of LV structure and function that define cardiomyopathy to the frequency of mitochondrial DNA mutations in cells from these same patients. A nested-case-control study design of mitochondrial mutations will be used to assess the relationship between HAART, mitochondrial compromise, and LV structure and function. Treatment intensity for both HAART and non-HAART regimens will be captured through a cumulative score based on an existing 8-point ordinal scale. Intensity will be measured at three points in time: 1) in utero; 2) during the first year of life; and 3) after the first year of life. Analysis of the longitudinal echocardiographic and mitochondrial data will provide valuable information about dose intensity and the comparative impact of HAART versus less aggressive drug regimens. It will also provide information on the impact of therapy during different stages of child development. Similar longitudinal data on viral load and duration of HIV will enable the investigators to control for the effects of HIV infection on cardiovascular toxicity. The findings will help determine the need for cardiovascular follow-up, prevention, and therapeutic trials.

  Eligibility

Ages Eligible for Study:   2 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Study participants will be children perinatally infected with HIV who were enrolled in the Women and Infants Transmision Study (WITS).

This cohort will be compared to the historical Pediatric Pulmonary and Cardiovacular Complications Study (P2C2 HIV) cohort of perinatally HIV-infected children not exposed to HAART.

Criteria

Inclusion Criteria:

  • HIV-infected children
  • Mothers of children understand and are willing to provide informed consent
  • Mothers of children are capable of answering in English or with the help of an interpreter

Exclusion Criteria:

  • HIV-infected child who is too young (less than 2 years of age) or otherwise unable to undergo an echocardiogram without sedation
  • Mothers of children have maternal diabetes or phenylketonuria
  • Mothers of children have a recognized Mendelian or chromosomal defect
  • Mothers of children are/were actively receiving chemotherapy for cancer during pregnancy
  • Mothers of children used lithium carbonate, anticonvulsants, amphetamines, or angiotensin converting enzyme (ACE) inhibitors on a chronic basis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00260806

Locations
United States, Florida
University of Miami Miller School of Medicine
Miami, Florida, United States, 33101
United States, Illinois
University of Illinois - Chicago
Chicago, Illinois, United States, 60612
United States, Maryland
Clinical Trials and Surveys Corp. (C-TASC)
Baltimore, Maryland, United States, 21210
United States, Massachusetts
Boston Children's Hospital
Boston, Massachusetts, United States, 02115
Boston Medical Center
Boston, Massachusetts, United States, 02118
United States, New York
State University of New York (SUNY)
Brooklyn, New York, United States, 11203
Columbia University
New York, New York, United States, 10027
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
Puerto Rico
University of Puerto Rico
San Juan, Puerto Rico
Sponsors and Collaborators
University of Miami
Clinical Trials & Surveys Corp (C-TASC)
Baylor College of Medicine
University of Illinois at Chicago
Columbia University
Boston Medical Center
Children's Hospital Boston
University of Puerto Rico
State University of New York
Investigators
Principal Investigator: Steven E. Lipshultz, MD University of Miami
  More Information

No publications provided

Responsible Party: Steven E. Lipshultz, MD, Voluntary Professor, University of Miami
ClinicalTrials.gov Identifier: NCT00260806     History of Changes
Other Study ID Numbers: 1318, R01HL078522, R01 HL78522
Study First Received: December 1, 2005
Last Updated: March 17, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on September 30, 2014