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

Left Ventricular Function in HIV-Negative Children Exposed to HIV and HAART In Utero

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections

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).

• Study Type: Observational
• Enrollment (Actual): 60

Contacts and Locations

Study Locations

• United States
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 12 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

HIV-negative children will be recruited through their HIV+ mothers who are seen at the AIDS Clinical Trials Unit at Washington University and surrounding St. Louis community clinics. HIV-negative children will be recruit through Washington University and surrounding St. Louis pediatric clinics, and through Washington University Volunteers for Health service.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Healthy Control; HIV-negative children born to healthy, HIV-negative women
Exposed to HIV/HAART; HIV-negative children exposed to HIV and HAART in utero

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left Ventricular Mass Index	left ventricular mass index measured by 2D echocardiography	Baseline
Fractional Shortening	Fractional shortening measured by M-mode cardiography	Baseline

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: William T Cade, PhD, Washington University School of Medicine

Publications and helpful links

General Publications

• Cade WT, Waggoner AD, Hubert S, Krauss MJ, Singh GK, Overton ET. Reduced diastolic function and left ventricular mass in HIV-negative preadolescent children exposed to antiretroviral therapy in utero. AIDS. 2012 Oct 23;26(16):2053-8. doi: 10.1097/QAD.0b013e328358d4d7.

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: April 19, 2010
• First Submitted That Met QC Criteria: April 19, 2010
• First Posted (Estimate): April 21, 2010

Study Record Updates

• Last Update Posted (Estimate): July 20, 2016
• Last Update Submitted That Met QC Criteria: June 8, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: HIV; children; heart function; HAART; in utero
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections
• Other Study ID Numbers: 10-0121