PHACS PH 100 SURVEILLANCE MONITORING FOR ART TOXICITIES STUDY IN HIV-UNINFEC

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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. Prospective cohort study designed to estimate the incidence of conditions and diagnoses potentially related to in utero exposure to antiretroviral therapy and/or exposure in the first two months of life among children born of HIV-infected mothers (source population). The study will use a registry approach to conduct active surveillance among children < 12 years of age at enrollment. Occurrences of abnormalities from ART exposure in utero and/or in the first two months of life will be sought in multiple domains, including metabolic, growth, cardiac, neurologic, neurodevelopmental, behavior, language, and hearing domains. Clinical and laboratory data will be examined for abnormalities through a hierarchy of evaluations: adverse events (AE) will be identified selected AEs will trigger predefined additional evaluations ? significant observations will be defined as cases a pattern of significant study-wide cases will be defined as signals. The incidence of these events of interest will be monitored over time and by ART regimen, and compared with historical data that may be suggestive of a signal. Some signals may be testable using existing and/or previously collected data, while other signals may indicate the need for additional hypothesis-driven studies outside of SMARTT. The SMARTT study will examine the toxicity of ART in HIV transmission prevention for the short-term toxicity of newer agents and combinations as well as the unanswered questions of longer term toxicity and subtle adverse effects. The specific aims of SMARTT are: To create a Static Surveillance Cohort to extend domain-specific data collection in children previously enrolled in WITS, PACTG 219C, P1025 and other similar pediatric cohort studies; To create a Dynamic Surveillance Cohort to examine domain-specific data of children newly exposed to ART in utero and/or in the first two months of life; To identify a set of "triggers" for each domain that define a "signal" of possible ART toxicity and compare the occurrence of these signals with previously collected data and by ART exposure; and To encourage and facilitate the development of hypothesis-driven studies to evaluate whether a "signal" is the result of ART exposure in utero and/or in the first two months of life. DOMAIN-SPECIFIC OBJECTIVES AND SPECIFIC AIMS General Objectives To assess growth and body composition, metabolic function, cardiac function, neurodevelopmental function as well as speech, language, hearing and other functions in HIV-uninfected children born of HIV-infected mothers with exposure to ART in utero and/or in the first two months of life. Metabolic Function and Growth To estimate the occurrence of abnormal signals of somatic growth and body composition: To estimate the occurrence of abnormal signals in measures of organ function, including the liver, muscles, and pancreas; and To evaluate other toxin exposures (e.g., licit and illicit drug exposure in utero or other toxins such as lead after birth) that may be alternative explanations for the signals described above. Cardiac Function: To identify signals of cardiac dysfunction in the cohort children. Neurologic, Neurodevelopmental, Behavior, Language, and Hearing: To identify age-specific signals of neurological, neurodevelopmental, linguistic, social, and behavioral dysfunction: Infancy. To identify neurological and neurodevelopmental signals in early cognitive, linguistic, and social function; Toddler. To identify signals of dysfunction in early cognitive skills, speech and language emergence, and behavioral functioning; Pre-school. To identify signals of neurodevelopmental/neurological impairments in cognitive, linguistic, behavior, and social abilities; and School age. To identify signals of dysfunction in cognitive development, and language, behavioral, social and executive function. To identify other neurologic conditions such as microcephaly, stroke, and febrile and non-febrile seizures. To identify adverse signals of hearing dysfunction. Other Domains of Interest: To identify diagnoses and conditions of interest not covered above that may be adverse signals. These include but are not limited to birth defects, unexplained death, and abnormalities of the hematopoeitic system.