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. The purpose of this study is to follow children and adolescents who are currently enrolled in or were previously enrolled in pediatric ACTG treatment perinatal or drug research studies to look for any late consequences of therapy in growth, neurologic and neuropsychologic function, long term survival, and quallity of life. The child is eligible for this study if the child is currently enrolled in, or was previously enrolled in a pediatric ACTG protocol or is currently enrolled in the Long Term Survivors of the Pediatric AIDS Foundation study being conducted at an ACTG site. This includes infants born to HIV infected mothers who were enrolled in an ACTG drug study when they were pregnant, regardless of whether or not definite HIV infection status in the infant is known. All children are eligible to be followed until their 21st birthday. There are several key hypotheses listen below that this late outcomes protocol plans to address in relation to pediatric interventions. In addition, it is also anticipated that the longitudinal data gathered in this protocol will enable investigators in the pediatric ACTG to answer other research questions and hypotheses specific to treatment in perinatal protocols in which they are involved. Perinatal Group: There will be no signficiantly increased prevalence of late organ abnormality/toxicity (focus on system with high mitochondrial contact - heart, liver, muscle), birth defects or neoplasms (i.e. vaginal tumor, pap smear abnormality) among ultimately uninfected infants exposed to zidovudine (or other study treatments) in utero compared to prevalence rates among comparable pediatric populations in the United States who were not exposed in utero to zidovudine (or other study treatments). For infants enrolled in ACTG 076, the comparison to prevalence rates will be for uninfected children who received placebo. For other future studies, comparison to national prevalence rates may need to be used. Among uninfected infants on ACTG 076, there will be no significant differences in growth or development among infants whose mothers received ZDV compared to those whose mother's received placebo during pregnancy: a.) growth (weight, height, head circumference) b.) pubertal development (Tanner staging, age of first menses) c.) mean neurocognitive scores on Bayley and later cognitive tests. Among infected children from ACTG 185, there will be no difference in disease progession betweent hose whose mothers received HIVIG compared to those whose mothers received IVIG. Disease progression is defined by clinical (i.e. AIDS-defining illness, death), immunologic (i.e. age-adjusted CD4+count), and virologic (quantitative central load via testing of ACTG 219 stored specimens, test to be determined) parameters. HIV Infected Group: There will be differences in rates of long term cumulative dose-related drug specific organ system toxicities related to specific drug therapies. For example, hepatic, cardiac or muscle toxicity will be more likely to occur with chronic ZDV therapy compared to other antiretroviral therapies; peripheral neuropathy will be more likely to be seen with chronic ddI, or ddC use; and ddI, ddC or 3TC will be more likely to be associated with pancreatic abnormalities. Initial combination therapy as compared to montherapy (e.g., using a randomization treatment protocol such as ACTG 152, 239 and 300) will result in significantly increased long term survival and improved physical growth and quality of life, as measured by length of survival, mean growth percentiles for height, weight and head circumference, and median scores on quality of life instruments. Initial use of combination therapy in infancy (0-24 months) (e.g., ACTG 152 or 239) will result in fewer neurology diagnoses and signficiantly higher mean neurocognitive scores at age 4 and 7 years compared to initial use of antiretroviral monotherapies. For children from Protocol 128 (followed up at 5-7 years post enrollment on 128) there will continue to be no significant differences in neurocognitive scores on the WISC-R between treatment arms. Advances in drug/biologic interventions, prophylaxis and treatment regimens for opportunistic infecious diseases and improved supportive care over time will result in significantly increased survival, improved growth adn development, decreased morbidity, and improved quality of life for successive cohorts of children involved in ACTG protocols. This will be assessed by comparing survival, median growth percentiles, median CD4+ percentages and quality of life scores at ages 2, 4, 7, 15, and 20 years for successive cohorts (e.g., assessed serially every 3 to 5 years) of pediatric subjects exposed to drugs/biologics in ACTG protocols.
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