The Coordinating Center (CC) of the PHACS consists of the PI, project director, and a group of leading investigators comprising the Scientific Leadership Group (SLG). Together with the Data Operations Center, the CC will establish the leadership structure of the PHACS including an Executive Committee (EC), an External Oversight Committee, and the SLG. The EC will be the main governing body of the PHACS and will provide oversight and final approval for all group activities. The CC will be responsible for overall management of the PHACS. The SLG will be responsible for defining the scientific agenda of the PHACS and, during year 1, the development of the two protocols which will address this agenda, each with its own cohort of subjects, specific objectives, and sub-studies. The Drug Toxicity Surveillance System will evaluate the safety of preventive antiretroviral therapy when administered to HIV-exposed infants in utero and in the newborn period. This will be an open protocol with ongoing accrual;initially subjects will be enrolled from the WITS and PACTG 219c studies. It will generate a cohort of HIV-uninfected children who will be monitored longitudinally for the development of mitochondrial disease, abnormalities in growth and development, and other end-organ disease. The Base Protocol will address the impact of HIV-infection on sexual maturation, pubertal development, and socialization of perinatally HIV-infected preadolescents and adolescents and define the course of perinatal HIV infection during adolescence. It will be a closed cohort, consisting of subjects 7-16 years of age who were previously enrolled in WITS and 219c. The Base Protocol will be fully coordinated with the CDC Legacy Project in order to expand the population available to study uncommon events. Once the protocols are developed in year one, a variety of focused sub-studies, utilizing one or both of the cohorts, will be developed by the SLG in order to address a variety of specific scientific questions. For the Base Protocol cohort, these include: neurodevelopmental and academic/vocational outcomes;changes in growth, development, body composition, and metabolism;mitochondrial disease and other toxicities resulting from ART;hyperlipidemias, other cardiac risk factors, and cardiovascular complications;reproductive and gynecologic outcomes and HPV infections;and infectious and non-infectious complications of HIV infection.