Clinical trial NCT00260806: Long-term Effects of Highly Active Anti-Retroviral Therapy on HIV-Infected Children
Official title: HAART Associated Cardiotoxicity in HIV-Infected Children
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV Infections
Lead sponsor: University of Miami
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Clinical Trials & Surveys Corp (C-TASC)
name: Baylor College of Medicine
name: University of Illinois at Chicago
name: Columbia University
name: Boston Medical Center
name: Boston Children's Hospital
name: University of Puerto Rico
name: State University of New York
First posted: 2005-12-02
Enrollment: 71
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief 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).

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 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

Primary outcomes:
measure: Cardiac systolic function
timeFrame: Measured from 2 years of age to 18 years of age
Secondary outcomes:
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Chicago
country: United States
facility: University of Illinois - Chicago
state: Illinois
city: Baltimore
country: United States
facility: Clinical Trials and Surveys Corp. (C-TASC)
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Brooklyn
country: United States
facility: State University of New York (SUNY)
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico
Study officials:
affiliation: University of Miami
name: Steven E. Lipshultz, MD
role: PRINCIPAL_INVESTIGATOR
References: