Evaluating Indicators of Cardiac Function in Children Living With HIV in Western Kenya

Research Summary:

1. Protocol Title: Evaluating Indicators of Cardiac Function in Children Living with Human Immunodeficiency Virus in Western Kenya
2. Purpose of Study: To determine the association of biomarker levels and relevant HIV history with cardiac function in HIV infected children attending Moi Teaching and Referral Hospital (MTRH) clinic.
3. Background & Significance:

HIV-associated cardiomyopathy is a disease that exposes children with the infection to tremendous morbidity and mortality. Detection of cardiomyopathy is limited by traditional echocardiographic measures (i.e. left ventricular ejection fraction, LVEF), which do not detect cardiomyopathy until late stages of disease. Therefore, a critical need exists to determine HIV-associated cardiomyopathy risk through early detection. Prior to changes in traditional echocardiographic measures, newer cardiac imaging techniques such as myocardial deformation imaging (ie strain measurements) can detect decreased myocardial performance when LVEF is still normal. The lack of methods to detect early myocardial dysfunction and biomarkers that determine risk are major barrier for outcomes and treatment research.

Myocardial deformation imaging represents a promising means to identify early dysfunction, but to date there have been no large studies using strain to assess cardiac function in children with HIV. Further, none have established predictors of worse cardiac function such as viral burden, immune status, zidovudine-containing ART regimens, and inflammatory state. This large-scale investigation utilizing the latest imaging techniques in evaluating cardiac function will provide first-in-kind data enabling estimation of prevalence of early HIV-associated cardiomyopathy as well as risk stratification. The study will explore the NIH/HIV High Priority Target area of HIV-associated cardiac co-morbidities and will enhance understanding of the relationship between cardiac function and viremia. Although these data will substantively enhance our understanding of early disease progression in children with subclinical HIV-associated cardiomyopathy, my long-term objective is to use these data in support of future work focused on early initiation of potentially, life altering therapies (such as angiotensin-converting enzyme inhibitor and digoxin medications) to children at highest risk for HIV-associated cardiac dysfunction in Africa and other resource poor regions of the world.

The proposal objective is to determine the association of biomarker levels, myocardial deformation, and viral load level history in children with perinatally acquired HIV. Our central hypothesis is that risk of abnormal myocardial strain can be defined in terms of HIV clinical parameters - including viral load, antiretroviral therapy (ART), CD4 count, and serum biomarkers (such as b-natriuretic peptide, BNP). The investigators will accomplish our objectives with the following Specific Aims: