Long-term Effects of Highly Active Anti-Retroviral Therapy on 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).
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||HAART Associated Cardiotoxicity in HIV-Infected Children|
- 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.
|Study Start Date:||August 2004|
|Study Completion Date:||June 2006|
|Primary Completion Date:||June 2006 (Final data collection date for primary outcome measure)|
Children perinatally infected with HIV with exposure to highly active anti-retroviral therapy (HAART).
Children with perinatally acquired HIV infection enrolled on the P2C2 Study, not exposed to HAART therapy.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00260806
|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 Medical Center|
|Boston, Massachusetts, United States, 02118|
|Boston Children's Hospital|
|Boston, Massachusetts, United States, 02115|
|United States, New York|
|State University of New York (SUNY)|
|Brooklyn, New York, United States, 11203|
|New York, New York, United States, 10027|
|United States, Texas|
|Baylor College of Medicine|
|Houston, Texas, United States, 77030|
|University of Puerto Rico|
|San Juan, Puerto Rico|
|Principal Investigator:||Steven E. Lipshultz, MD||University of Miami|