Perinatally HIV-infected children provide a unique model system to study the chronic effects of growing up with HIV. We propose to re-enroll 500 HIV-infected children age 5-9 years at two treatment sites in Johannesburg, South Africa. These children are prior participants in clinical studies who initiated therapy during the first two year of life and have detailed clinical information, HIV-related laboratory results and over 10,000 blood specimens stored in repositories. We will prospectively follow the re-enrolled children and collect standardized clinical data on co-morbidities, toxicities and complications, laboratory data on HIV-related parameters and blood samples and other specimens for special studies. We will also enroll a cross-sectional sample of 250 uninfected children (household/sibling controls) frequency-matched by age within 3-month intervals to the re- enrolled children at the time of recruitment. We will integrate the newly-collected, follow-up data and samples with the historical databases and repositories to provide a platform to investigate (1) host epigenetics and (2) mitochondrial function and their relations with HIV disease progression, drug regimens, and metabolic complications in HIV-infected children. First, using well-established array-based methods and pyrosequencing, we propose to identify the spectrum of gene-specific DNA methylation changes that accompany perinatally- acquired HIV infection and HIV treatment. Second, utilizing both stored and newly-collected specimens, we propose to test whether mitochondrial dysfunction (as measured by novel methods of enzyme function and cell stress) exacerbates chronic inflammation and immune senescence underlying HIV disease progression and the metabolic complications that may accompany long-term treatment. Our prospective cohort, building on an extensive and well-characterized perinatally-infected population, will provide a valuable resource to undertake these and future pathogenesis-oriented studies to inform development of complementary interventions to improve long-term outcomes of HIV-infected children in sub-Saharan Africa.

Public Health Relevance

We will combine newly-collected prospective data from perinatally HIV-infected children now of school-age with already collected clinical and repository data collected prospectively from the time of treatment initiation. The cohort will provide a platform to study the role of host epigenetics and mitochondrial function in HIV progression and metabolic complications of long-term, treated HIV infection.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD073952-04
Application #
8898166
Study Section
Special Emphasis Panel (ZHD1)
Program Officer
Lorenzo, Eric
Project Start
2012-08-01
Project End
2016-07-31
Budget Start
2015-08-01
Budget End
2016-07-31
Support Year
4
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Neurology
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Ramteke, Sarah M; Shiau, Stephanie; Foca, Marc et al. (2018) Patterns of Growth, Body Composition, and Lipid Profiles in a South African Cohort of Human Immunodeficiency Virus-Infected and Uninfected Children: A Cross-Sectional Study. J Pediatric Infect Dis Soc 7:143-150
Shiau, Stephanie; Strehlau, Renate; Shen, Jing et al. (2018) Biomarkers of Aging in HIV-Infected Children on Suppressive Antiretroviral Therapy. J Acquir Immune Defic Syndr 78:549-556
Shiau, Stephanie; Webber, Acadia; Strehlau, Renate et al. (2017) Dietary Inadequacies in HIV-infected and Uninfected School-aged Children in Johannesburg, South Africa. J Pediatr Gastroenterol Nutr 65:332-337
Ramteke, Sarah M; Kaufman, Jonathan J; Arpadi, Stephen M et al. (2017) Unusually High Calcaneal Speed of Sound Measurements inĀ Children with Small Foot Size. Ultrasound Med Biol 43:357-361
Murnane, Pamela M; Strehlau, Renate; Shiau, Stephanie et al. (2017) Switching to Efavirenz Versus Remaining on Ritonavir-boosted Lopinavir in Human Immunodeficiency Virus-infected Children Exposed to Nevirapine: Long-term Outcomes of a Randomized Trial. Clin Infect Dis 65:477-485
Murnane, Pamela M; Sigamoney, Stacy-Lee; Pinillos, Francoise et al. (2017) Extent of disclosure: what perinatally HIV-infected children have been told about their own HIV status. AIDS Care 29:378-386
Wong, Marcia; Shiau, Stephanie; Yin, Michael T et al. (2016) Decreased Vigorous Physical Activity in School-Aged Children with Human Immunodeficiency Virus in Johannesburg, South Africa. J Pediatr 172:103-9
Arpadi, Stephen M; Shiau, Stephanie; Strehlau, Renate et al. (2016) Efavirenz is associated with higher bone mass in South African children with HIV. AIDS 30:2459-2467
Shiau, Stephanie; Kuhn, Louise; Strehlau, Renate et al. (2014) Sex differences in responses to antiretroviral treatment in South African HIV-infected children on ritonavir-boosted lopinavir- and nevirapine-based treatment. BMC Pediatr 14:39