Heart Function in HIV-Negative Children Exposed to HIV and HAART

Completed

Conditions: HIV Infections

Registration Number: NCT01107834

Lead Sponsor: Washington University School of Medicine

Brief Summary: HIV-uninfected children born to HIV+ women have low level heart problems at birth which may predispose them to heart failure, arrythmias and heart attack later in life. The impact of these heart problems on future heart health is unclear as it is unknown if heart problems in these children persist, worsen or resolve in pre-pubescence. The objective of this study is to characterize heart function in HIV-negative pre-pubertal children born to HIV+ women and exposed to HIV and HAART in utero and compare them to age and gender matched healthy children born to HIV-negative women. Through this objective we will determine if heart problems in HIV-negative children born to HIV+ women and exposed to HAART in utero persists, worsens, or resolves during pre-pubescence.

Detailed Description: Significance:

Approximately 700,000 children annually are born to HIV-infected mothers throughout the world, but with the advent of perinatal highly active antiretroviral therapy (HAART), the majority of children are born uninfected in Westernized nations and those uninfected are increasing in developing nations. Uninfected children exposed to HIV and HAART in utero, have subclinical left ventricular dysfunction (LVD) at birth which may predispose them to heart failure, conduction abnormalities and myocardial infarction later in life. The impact of this LVD on future cardiac risk is unclear as it is unknown if LVD in these children persist, worsen or resolve in pre-pubescence.

Study objectives:

The objective of this study is to characterize left ventricular function in HIV-negative pre-pubertal children born to HIV+ women and exposed to HIV and HAART in utero and compare them to age and gender matched healthy children born to HIV-negative women. Through this objective we will determine if LVD in HIV-negative children born to HIV+ women and exposed to HAART in utero persists, worsens, or resolves during pre-pubescence. If LVD persists or worsens in pre-pubescence, these data will lead to future studies examining mechanisms of and treatments for LVD in these children and will significantly impact the clinical monitoring and care of these children. If LVD resolves during pre-pubescence, then these data will provide important information that clinical cardiac monitoring may not be critical in this population.

Methods:

We plan to examine left ventricular function in 30 HIV-negative children born to HIV+ women and exposed to HAART in utero and compare them to 30 healthy age and gender matched children born to HIV-negative women. Left ventricular function will be examined by 2-D, Doppler and Tissue Doppler imaging echocardiography using a General Electric Vivid 7® ultrasound machine. Left ventricular measures will include left ventricular structure and dimensions, systolic and diastolic flow rates, wall velocities during systole and diastole and systolic and diastolic strain and strain rates (sensitive measures of myocardial contractility). Echocardiographic measures will take place in the Cardiovascular Imaging Laboratory (CVIL) at Washington University School of Medicine by a certified cardiac ultrasonographer and data will be processed, analyzed and interpreted by the ultrasonographer, a consulting cardiologist and the principal investigator.

Outcomes:

Primary outcomes will include measures of left ventricular function: left ventricular mass, left ventricular end diastolic dimension, fractional shortening, systolic and diastolic wall velocities (tissue Doppler imaging) and systolic and diastolic strain and strain rates (2-D speckle tracking methodology).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 60

Inclusion Criteria

Age 5-12 years
Tanner stage I-III
Born to HIV+ mother
No HIV infection
Had taken standard of care prophylactic HAART at birth-1 month of age
Child currently not taking medications or have medical diagnosis that would affect left ventricular function
Mother was taking HAART during pregnancy (standard of care)
Mother was not using illegal drugs during pregnancy
No intrauterine growth restriction diagnosis during pregnancy
During pregnancy, mother will not have a diagnosis of type 2 diabetes or gestational diabetes.

Exclusion Criteria

Age 5-12 years
Tanner stage I-III
Born to HIV-negative mother
Mother was not a frequent exerciser during pregnancy (>2x/week)
Mother will not have gestational diabetes or a diagnosis of type 2 diabetes during pregnancy of the child being studied
Child currently not taking medications or have medical diagnosis that would affect left ventricular function

Study & Design

Study Type: OBSERVATIONAL

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Left Ventricular Mass Index	Baseline	left ventricular mass index measured by 2D echocardiography
Fractional Shortening	Baseline	Fractional shortening measured by M-mode cardiography

Secondary Outcome Measures

Name	Time	Method
Myocardial Wall Velocity During Early Diastole	Baseline	Myocardial wall velocity during early diastolemeasured by tissue Doppler imaging
Early to Late Diastolic Filling Ratio	Baseline	Early to late diastolic filling ratio measured by tissue Doppler echocardiography
Global Strain Rate	Baseline	Myocardial deformation (a measure of heart contractility) measured by speckel tracking echocardiography
Systolic Myocardial Velocity During Systole (S')	Baseline	Systolic myocardial velocity during systole measured by tissue Doppler echocardiography