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

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ClinicalTrials.gov Identifier: NCT00260806
Recruitment Status : Completed
First Posted : December 2, 2005
Last Update Posted : March 18, 2014
Information provided by (Responsible Party):

December 1, 2005
December 2, 2005
March 18, 2014
August 2004
June 2006   (Final data collection date for primary outcome measure)
Cardiac systolic function [ Time Frame: Measured from 2 years of age to 18 years of age ]
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Complete list of historical versions of study NCT00260806 on ClinicalTrials.gov Archive Site
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Long-term Effects of Highly Active Anti-Retroviral Therapy on HIV-Infected Children
HAART Associated Cardiotoxicity in HIV-Infected Children
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).


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.


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.

Observational Model: Cohort
Time Perspective: Prospective
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Retention:   Samples With DNA
Peripheral blood mononuclear cells (PBMCs) were collected from the WITS cohort to investigate the presence of mitochondrial DNA (mtDNA) mutations.
Non-Probability Sample

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.

HIV Infections
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  • 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.
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
June 2006
June 2006   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
2 Years to 18 Years   (Child, Adult)
Contact information is only displayed when the study is recruiting subjects
Puerto Rico,   United States
R01HL078522 ( U.S. NIH Grant/Contract )
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Steven E. Lipshultz, MD, University of Miami
University of Miami
  • National Heart, Lung, and Blood Institute (NHLBI)
  • Clinical Trials & Surveys Corp (C-TASC)
  • Baylor College of Medicine
  • University of Illinois at Chicago
  • Columbia University
  • Boston Medical Center
  • Boston Children’s Hospital
  • University of Puerto Rico
  • State University of New York
Principal Investigator: Steven E. Lipshultz, MD University of Miami
University of Miami
March 2014