This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a prospective cohort study designed to define the impact of HIV infection and antiretroviral therapy on pre-adolescents and adolescents with perinatal HIV infection. A group of HIV-uninfected children with perinatal exposure to HIV from a similar sociodemographic background and age distribution will be enrolled for comparison. Domains to be investigated include growth and sexual maturation, metabolic risk factors for cardiovascular disease, cardiac function, bone health, neurologic, neurodevelopment, language, hearing and behavioral function, and human papillomavirus (HPV) infection. The impact of HIV infection and its treatment on the growth and development of children who have been living with HIV infection since birth is not fully known. The PHACS AMP protocol is designed to study the effect of HIV infection on key processes of maturation such as pubertal development, bone growth, fat distribution, and hepatic, renal and cardiovascular functions. In addition, behavior in adolescents plays a major role in adherence to medications, treatment failure, evolution of viral resistance, and secondary transmission of HIV, including the transmission of resistant virus, to others. This knowledge can form the basis for interventions to improve the quality of life of infected children. Unfortunately, the number of HIV-infected infants, children and adolescents worldwide is growing substantially in both resource-poor countries and in countries with increasing levels of health care. Thus the information gained from this study will benefit the increasing number of infected youth worldwide. To define the impact of HIV infection and ART on growth and pubertal development (and their hormonal regulation), along with the cognitive, academic, and social development, of pre-adolescents and adolescents with perinatal HIV infection as they move through adolescence into adulthood. To identify infectious and non-infectious complications of HIV disease and evaluate their associations with ART. These include toxicities resulting from ART, including mitochondrial toxicity, lipid abnormalities, and end-organ damage. To longitudinally track height, weight, body mass index (BMI), and sexual maturation in perinatally exposed HIV-infected and uninfected children and to correlate measurements with parental stature (if available), lifestyle (diet and physical exercise), and disease and treatment status. Perinatally HIV-infected children who reach adolescence manifest reduced growth, and delayed onset and altered trajectory of sexual maturation compared to HIV-exposed but uninfected children of similar socioedemographic background. An association exists between abnormal CV structure and function and mtDNA mutations and suggests that mitochondrial abnormalities may lead to impaired CV functioning.
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