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

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).

Inclusion Criteria:

1. Age 5-12 years

2. Tanner stage I-III

3. Born to HIV+ mother

4. No HIV infection

5. Had taken standard of care prophylactic HAART at birth-1 month of age

6. Child currently not taking medications or have medical diagnosis that would affect
left ventricular function

7. Mother was taking HAART during pregnancy (standard of care)

8. Mother was not using illegal drugs during pregnancy

9. No intrauterine growth restriction diagnosis during pregnancy

10. During pregnancy, mother will not have a diagnosis of type 2 diabetes or gestational
diabetes.

Exclusion Criteria:

1. Age 5-12 years

2. Tanner stage I-III

3. Born to HIV-negative mother

4. Mother was not a frequent exerciser during pregnancy (>2x/week)

5. Mother will not have gestational diabetes or a diagnosis of type 2 diabetes during
pregnancy of the child being studied

6. Child currently not taking medications or have medical diagnosis that would affect
left ventricular function