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

HIV Infections Clinical Trial

Official title:

HAART Associated Cardiotoxicity in HIV-Infected Children

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00260806
• Other study ID #: 1318
• Secondary ID: R01HL078522
• Status: Completed
• Phase: N/A
• First received: December 1, 2005
• Last updated: March 17, 2014
• Start date: August 2004
• Est. completion date: June 2006

Study information

• Verified date: March 2014
• Source: University of Miami
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 71
• Est. completion date: June 2006
• Est. primary completion date: June 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 18 Years

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• HIV Infections

Locations

Country	Name	City	State
Puerto Rico	University of Puerto Rico	San Juan
United States	Clinical Trials and Surveys Corp. (C-TASC)	Baltimore	Maryland
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Boston Medical Center	Boston	Massachusetts
United States	State University of New York (SUNY)	Brooklyn	New York
United States	University of Illinois - Chicago	Chicago	Illinois
United States	Baylor College of Medicine	Houston	Texas
United States	University of Miami Miller School of Medicine	Miami	Florida
United States	Columbia University	New York	New York

Sponsors (10)

Lead Sponsor	Collaborator
University of Miami	Baylor College of Medicine, Boston Medical Center, Children's Hospital Boston, Clinical Trials & Surveys Corp (C-TASC), Columbia University, National Heart, Lung, and Blood Institute (NHLBI), State University of New York, University of Illinois at Chicago, University of Puerto Rico

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cardiac systolic function		Measured from 2 years of age to 18 years of age	No